Age,a basic marker of the population,is an indispensable demographic characteristic in medicine.However,the grouping in medicine according to age have problems such as inconsistent grouping criteria and ambiguous definition of age-related terms.Therefore,this article reviews the age-based grouping criteria and the application of related terms in medicine.

Objective To investigate the expression regulation of autophagy-related genes(ATG)and the mechanism of autophagy in rheumatoid arthritis(RA). Methods The differentially expressed genes(DEG)of RA were identified from GSE55235 and GSE55457,on the basis of which the differentially expressed autophagy-related genes(DE-ATG)were selected from the Human Autophagy Database.STRING 11.0 and GeneMANIA were used to establish protein-protein interaction networks.Further,the transcription factor-gene-miRNA co-expression network was established via NetworkAnalyst and Cytoscape.Finally,receiver operating characteristic(ROC)curve and DrugBank were employed to evaluate the efficacy of the predicted biomarkers and the performance of drugs targeting DE-ATG.GraphPad Prism 8.2.1 and R 4.0.3 were used for statistical analysis and graphics. Results A total of 485 DEG were enriched in signaling pathways such as T cell activation,hormone regulation,osteoclast differentiation,RA,and chemokines.Eleven DE-ATG regulated the expression of RUNX1,TP53,SOX2,and hsa-mir-155-5p in synovial tissues of RA patients and were involved in the response to environmental factors such as 2,3,7,8-tetrachlorodibenzodioxin and silicon dioxide.The ROC curve analysis identified the DE-ATG with good sensitivity and specificity,such as MYC,MAPK8,CDKN1A,and TNFSF10,which can be used to distinguish certain phenotypes and serve as novel biomarkers for RA. Conclusions In RA,down-regulated DE-ATG expression may promote apoptosis and lysis of chondrocytes.The identified novel biomarkers provides new ideas and methods for diagnosing and treating RA.The establishment of transcription factor-miRNA-gene co-expression network provides direct evidence for dissecting synovial inflammation and articular cartilage destruction.

To improve the diagnosis of atypical lymphocytes and reduce the misdiagnosis rate,we analyzed the medical records of 2 cases with cell morphology suggestive of atypical lymphocytes.One case was diagnosed with infectious mononucleosis and the other with aggressive NK cell leukemia.The purpose of this paper is to emphasize that the diagnosis of atypical lymphocytes based only on morphological interpretation of cells may be incorrect,which should be combined with clinical symptoms,signs,imaging examination,cell immunophenotype,and disease outcome.

Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.

As the incidence of diabetes mellitus is rapidly increasing worldwide,that of related complications,such as diabetic kidney disease(DKD),also increases,conferring a heavy economic burden on the patients,families,society,and government.Diabetes mellitus complicated with chronic kidney disease(CKD)includes DKD and the CKD caused by other reasons.Because of the insufficient knowledge about CKD,the assessment of diabetes mellitus complicated with CKD remains to be improved.The therapies for diabetes mellitus complicated with CKD focus on reducing the risk factors.In clinical practice,DKD may not be the CKD caused by diabetes.According to clinical criteria,some non-diabetic kidney disease may be misdiagnosed as DKD and not be treated accurately.This review summarizes the status quo and research progress in the assessment,diagnosis,and treatment of diabetes mellitus complicated with CKD and predicts the directions of future research in this field.

Objective To clarify the hotspots and trends of multimorbidity research and to provide evidence for further research in China. Methods Papers on multimorbidity were retrieved from PubMed and Web of Science (from inception to August 11,2021).BICOMB and gCLUTO were used for bibliometric and clustering analysis,and CiteSpace was employed for analysis of authors and citations,and burst detection of keywords. Results The research on multimorbidity has been on the rise.Among the authors,Mercer SW published the most papers on this topic and Fortin M was the most cited author.Karolinska Institute topped the institutions in the number of published papers,and the paper published in Lancet by Barnett K in 2012 was the most cited.A total of 75 high-frequency keywords were extracted,on the basis of which seven research hotspots were summarized:epidemiology (including the prevalence and trend),medication (involving polypharmacy,medication compliance,etc.),medical expenditure (including cost and medical services),aging (such as elderly patients,frailty,and disability),psychology (involving mental health,social support,etc.),multimorbidity management (such as the treatment,primary health care,and integrated care),and comorbidity of cardiovascular and metabolic diseases (involving obesity,stroke,diabetes,etc.). Conclusions Multimorbidity is concerned as a major health threat and public health problem worldwide.The management of multimorbidity is more complex than that of one disease,which thus faces more challenges.Therefore,researchers,health care providers,and policy-makers should underscore it.

Objective To analyze the risk factors and build a clinical prediction model for hemodynamic depression (HD) after carotid artery stenting (CAS). Methods A total of 116 patients who received CAS in the Department of Vascular Surgery,Drum Tower Clinical College of Nanjing Medical University and the Department of Vascular Surgery,the Affiliated Suqian First People’s Hospital of Nanjing Medical University from January 1,2016 to January 1,2022 were included in this study.The patients were assigned into a HD group and a non-HD group.The clinical baseline data and vascular disease characteristics of each group were collected,and multivariate Logistic regression was employed to identify the independent predictors of HD after CAS and build a clinical prediction model.The receiver operating characteristic (ROC) curve was drawn,and the area under the ROC curve (AUC) was calculated to evaluate the predictive performance of the model. Results The HD group had lower proportions of diabetes (P=0.014) and smoking (P=0.037) and higher proportions of hypertension (P=0.031),bilateral CAS (P=0.018),calcified plaque (P=0.001),eccentric plaque (P=0.003),and the distance<1 cm from the minimum lumen level to the carotid bifurcation (P=0.009) than the non-HD group.The age,sex,coronary heart disease,symptomatic carotid artery stenosis,degree of stenosis,and length of lesions had no statistically significant differences between the HD group and the non-HD group (all P>0.05).Based on the above predictive factors,a clinical prediction model was established,which showed the AUC of 0.807 and the 95% CI of 0.730-0.885 (P<0.001).The model demonstrated the sensitivity of 62.7% and the specificity of 87.7% when the best cut-off value of the model score reached 12.5 points. Conclusions Diabetes,smoking,calcified plaque,eccentric plaque,and the distance<1 cm from the minimum lumen level to the carotid bifurcation are independent predictors of HD after CAS.The clinical prediction model built based on the above factors has good performance in predicting the occurrence of HD after CAS.

Circular RNAs (circRNAs),a group of highly conserved small RNAs,are characterized by a closed circular structure from precursor linear RNA through reverse splicing.They are powerful regulators of the physiological and pathological processes in organisms at different development stages.Zebrafish can be used for the high-throughput drug screening with low cost.Thus,the circRNAs associated with development and inflammation can be mined from zebrafish.Recently,a variety of circRNAs in zebrafish have been identified and characterized.Studies have proved that circRNAs play a vital role in the development and inflammation of zebrafish.The paper summarizes the classification,characteristics,and biological functions of circRNAs,and reviews the research progress in zebrafish’s circRNAs.

Sarcopenia is a common geriatric syndrome associated with the occurrence of adverse consequences such as falls,debility,and death,seriously affectingthe quality of life of the elderly.Oral health as the basis of the overall health plays a vital role in improving the overall quality of life and extending the healthy life span of the elderly.Studies have demonstrated that poor oral health may increase the risk of sarcopenia.By reviewing the recent studies about oral health and sarcopenia in the elderly,we summarize the related mechanisms and put forward some intervention measures,so as to provide a theoretical basis for the prevention and treatment of sarcopenia from the aspect of oral health.

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Ferroptosis is a new type of programmed cell death different from other cell death pathways such as apoptosis,autophagy,necrosis,and pyroptosis in terms of initiation,mechanisms,and molecular characteristics.As the accumulation of phospholipid hydroperoxides is the hallmark of ferroptosis,the balance between oxidative damage and antioxidant defense is critical to the regulatory mechanism of ferroptosis.In cancer,the upregulation of antioxidant defense pathways can inhibit ferroptosis,thereby promoting cancer cells to survive the oxidative stress and develop drug resistance.This review systematically introduces the main features and regulatory mechanisms of ferroptosis.In addition,we summarize the role of ferroptosis in the progression and drug resistance of malignant tumors,providing novel implications for further research on the pathogenesis of malignant tumors and discovery of new targets for anti-cancer therapy.

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e’) (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e’ ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.

Community-based home hospice care provided by community service centers and family physician teams aims to alleviate the suffering of terminally ill patients and help them to receive end-of-life care and pass away at home.The Puhuangyu Community Health Service Center established the home hospice care model of PUMCH-Puhuangyu Coordination at the end of 2019.The model has been practiced and improved to date.This paper introduces this model of home hospice care.

Air pollution has severe detrimental effects on public health.A substantial number of studies have demonstrated that air pollution exposure is a risk factor for the occurrence of cardiovascular and cerebrovascular diseases and a cause of non-communicable diseases.Both long-term and short-term exposure to air pollution are associated with respiratory diseases,stroke,coronary artery disease,and diabetes.Aiming to better understand the association,we reviewed the latest studies about the association of air pollution with cardiovascular and cerebrovascular diseases,especially stroke,coronary heart disease,arrhythmia,hypertension,and heart failure,and summarized the underlying mechanisms of the health damage caused by long-term and short-term exposure to air pollution.

Sepsis,a syndrome characterized by organ dysfunction caused by infection,exhibits high incidence and mortality.The pathogenesis of sepsis is complex and involves a cascade of immune reactions,with no specific drugs currently available.Sepsis is mainly treated with Western medical supportive therapies such as antibiotics,hemodynamic management,and mechanical ventilation.However,the occurrence of immune cascades significantly increases patients’ vulnerability to secondary infections,leading to septic shock and unfavorable prognoses.International consensus indicates that initiating dynamic monitoring of patients’ immune function within 48 h post-sepsis diagnosis can effectively decelerate sepsis progression.Extensive studies have indicated that macrophages,serving as the first line of defense in the innate immune system against pathogens,play a vital role in treating immune system disorders by regulating macrophage polarization and the ratio of cytokines activated.Mitophagy,a hot topic in recent years,has increasingly been shown to play a crucial role in regulating inflammatory signal transduction.Promoting mitophagy during the stage of cytokine storm can mitigate uncontrolled infection and excessive inflammation in sepsis,and inhibiting mitophagy during immunosuppression can enhance host immunity,facilitate bacterial clearance,and improve the survival rate of patients.The idea of treating disease before its onset in traditional Chinese medicine (TCM) coincides with the current consensus among sepsis experts on prevention and interception.The TCM therapies such as extracts of Chinese medicine decoction pieces,TCM compound prescriptions,and acupuncture and moxibustion have the effects of clearing heat and detoxifying,activating blood and resolving stasis,reinforcing healthy qi and consolidating root,and purging.These approaches dynamically regulate the levels of mitophagy-related proteins,such as phosphatase and tension homology-induced putative kinase 1,Parkin-E3 ubiquitin protein ligase,light chain 3,and p62,while maintaining a suitable ratio between M1 and M2 macrophages.Consequently,they effectively prevent,halt,or even reverse the progression of sepsis,offering a novel perspective on sepsis management by emphasizing prevention before disease onset and controlling development of existing disease.

Erectile dysfunction (ED) refers to the persistent inability to achieve and/or maintain a sufficient erection of the penis to obtain a satisfactory sexual life,which affects the quality of life of the patients and their sexual partners.To decipher the pathophysiological mechanism of ED,researchers have established a variety of animal models and achieved a series of progress.The cavernous nerve (CN) of rodents,anatomically similar to that of humans,is cost-effective,thick,and easy to be identified,which has gradually become the mainstream of animal models.In this paper,we reviewed the modeling methods of the neurological ED caused by bilateral CN injury in rats in recent years,summarized the model evaluation indicators,and discussed the application and progress of ED models in basic experimental research.

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

Objective To screen out the key genes leading to diabetic cardiomyopathy by analyzing the mRNA array associated with diabetic cardiomyopathy in the GEO database. Methods The online tool GEO2R of GEO was used to mine the differentially expressed genes (DEG) in the datasets GSE4745 and GSE5606.R was used to draw the volcano map of the DEG,and the Venn diagram was established online to identify the common DEG shared by the two datasets.The clusterProfile package in R was used for gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment of the DEG.GSEA was used for gene set enrichment analysis,and STRING for the construction of a protein-protein interaction network.The maximal clique centrality algorithm in the plug-in Cytohubba of Cytoscape was used to determine the top 10 key genes. The expression of key genes was studied in the primary cardiomyocytes of rats and compared between the normal control group and high glucose group. Results The expression of Pdk4,Ucp3,Hmgcs2,Asl6,and Slc2a4 was consistent with the array analysis results.The expression of Pdk4,Ucp3,and Hmgcs2 was up-regulated while that of Acsl6 and Slc2a4 was down-regulated in the cardiomyocytes stimulated by high glucose (25 mmol/L) for 72 h. Conclusion Pdk4,Ucp3,Hmgcs2,Asl6,and Slc2a4 may be associated with the occurrence and development of diabetic cardiomyopathy,and may serve as the potential biomarkers of diabetic cardiomyopathy.

Objective To analyze the clinical characteristics of collagenous gastritis (CG) and provide evidence for the precise diagnosis and treatment of CG.Methods Published case reports and case series were collected from PubMed,CNKI,and Wanfang Med Online with the key words of collagenous gastritis,collagenous gastroduodenitis,collagenous gastrointestinal diseases,and gastric mucosal nodules.The demographic and clinical information of each case was collected.Results According to the extent of collagen deposition in the digestive tract,94 CG cases included in this study were assigned into upper digestive tract (UDT)-CG,total digestive tract (TDT)-CG and other groups.The UDT-CG group included 52 cases (57.69% females and 42.31% males) with a median age of 14.50 (11.00,25.75) years old.There were 17 cases in the TDT-CG group,including 70.59% females and 29.41% males,with a median age of 15.00 (9.50,48.50) years old.The other group contained 25 cases,(64.00% females and 36.00% males) with a median age of 25.00 (15.50,59.50) years old.The main clinical manifestations in the UDT-CG group were anemia (59.62%) and diarrhea (17.31%),and those in the TDT-CG group were anemia (29.41%) and diarrhea (94.12%).The nodular appearance of gastric mucosa was observed in 75.00% cases in the UDT-CG group and 35.29% cases in the TDT-CG group.In the initial treatment,symptomatic therapy and hormonal therapy respectively relieved the symptoms in 75.00% (30/40) and 100% (3/3) cases in the UDT-CG group and 57.14% (4/7) and 83.33% (5/6) cases in the TDT-CG group.In the retreatment,symptomatic therapy and hormone therapy respectively achieved the remission rates of 100.00% (3/3) and 88.89% (8/9) in the UDT-CG group and 80.00% (4/5) and 66.67% (2/3) in the TDT-CG group.Conclusions CG,a rare disease of gastric collagen deposition,mainly occurs in young patients,and females are more susceptible than males.The clinical manifestations of CG are nonspecific,and anemia,abdominal pain,diarrhea,weight loss,and gastrointestinal bleeding are the common symptoms of CG.Nodular appearance of gastric mucosa is a relatively specific endoscopic feature of CG.There is no standardized treatment for CG.Symptomatic treatment is commonly adopted to improve the quality of life of the patients,and hormones can be added when necessary.

Autologous chimeric antigen receptor(CAR)T-cell therapy has improved the prognosis of hematological malignancies.Nevertheless,allogeneic CAR-T cells have potential advantages over the autologous approach available on the market.However,allogeneic CAR-T cells may cause life-threatening graft-versus-host disease(GVHD)or be rapidly eliminated by the host immune system.In this review,we analyze the different sources of T cells for optimal allogeneic CAR-T cell therapy,describe the different approaches,and introduce the gene editing measures to produce allogeneic CAR-T cells with limited potential for GVHD and improved anti-tumor effect.

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

Studies have demonstrated that the occurrence of a variety of arrhythmias presents an obvious circadian rhythm,which may be regulated by circadian rhythm genes.Circadian cycle and light stimulation can affect circadian rhythm genes and proteins,which constitute a transcription-translation loop that can regulate the ion channels in myocardial cell membrane through nervous-humoral regulation and changes in central clock-sub-clock gene expression,thereby modulating arrhythmia.This article reviews the molecular basis,mechanism,and performance of circadian rhythm in regulating arrhythmia.

Insulin resistance (IR) is a pathological reaction of hyperinsulinemia and impaired glucose tolerance caused by decreased sensitivity of target tissues such as liver to insulin.The pathogenesis of IR as a typical pathological feature of type 2 diabetes is the focus of anti-diabetes research.In this paper,we reviewed the molecular mechanisms of glucose and lipid metabolism,oxidative stress,mitochondrial dysfunction,endoplasmic reticulum stress,inflammation,and hepatic IR in the case of type 2 diabetes mellitus,which might provide new ideas and theoretical guidance for the treatment of diabetes mellitus.

Abdominal aortic aneurysm is defined as a dilated aorta with a diameter at least 1.5 times of the normal aorta.There is no effective drug for AAA.We summarized the high-risk factors,pathologic features,current therapies,and animal models in the pre-clinical study to gain comprehensive understanding of AAA.With this review,we aim to provide scientific support for the mining of therapeutic targets for AAA.

Objective To investigate the level of serum uric acid in patients with diabetes insipidus (DI),summarize the clinical characteristics of central diabetes insipidus (CDI) patients with hyperuricemia (HUA),and analyze the factors affecting the level of serum uric acid in the patients with CDI. Methods The clinical data of DI patients admitted to Peking Union Medical College Hospital from 2018 to 2021 were retrospectively analyzed.The patients were assigned into a child and adolescent group (≤ 18 years old) and an adult group (>18 years old) according to their ages.The demographic and biochemical data between two groups of patients with and without HUA were compared.Spearman correlation analysis and multiple linear regression analysis were performed to analyze the correlations between serum uric acid level and other factors. Results Among the 420 DI patients,411 patients had CDI (97.9%),including 189 patients with HUA (46.0%).Thirteen (6.9%) out of the 189 CDI patients with HUA presented the disappearance of thirst.The prevalence of HUA in children and adolescents was higher than that in adults (χ²=4.193,P=0.041).The level of serum uric acid in the CDI patients with HUA and disappearance of thirst was higher than those without disappearance of thirst (U=2.593, P=0.010).The multiple linear regression predicted serum creatinine (β=0.472,95%CI=2.451-4.381, P<0.001) and body mass index (β=0.387,95%CI=6.18-12.874, P<0.001) as the independent risk factors of serum uric acid level increment in children and adolescents,while serum creatinine ( β=0.361, 95%CI=1.016-1.785, P<0.001),body mass index (β=0.208, 95%CI=2.321-6.702, P<0.001),triglyceride ( β=0.268, 95%CI=12.936-28.840, P<0.001 ),and total cholesterol ( β=0.129, 95%CI=2.708-22.250, P=0.013 ) were the independent risk factors in adults. Conclusions The patients with CDI were more likely to have HUA,and the prevalence of HUA in children and adolescents was higher than that in adults.Body mass index,serum creatinine,triglyceride,total cholesterol,and disappearance of thirst were the risk factors for the increased level of serum uric acid in CDI patients.

Arterial cannulation can be used to monitor blood pressure in real time and facilitate frequent arterial blood gas analysis.It is one of the commonly used clinical techniques in anesthesia,emergency,and intensive care units.Studies have demonstrated that ultrasound guidance can increase the success rate of arterial cannulation and reduce the incidence of related complications.In recent years,ultrasound guidance technology has developed rapidly and is increasingly used in clinical practice.This article reviews the latest advances in the application of ultrasound guidance in radial artery cannulation.

Aplastic anemia (AA) and myelodysplastic syndrome (MDS) are clonal diseases with hemopoietic stem cell (HSC) abnormalities,which are sometimes difficult to be distinguished from each other.The development of molecular detection techniques has facilitated our understanding of the molecular pathogenesis of the two diseases.This article reviewed the somatic mutation (SM) and cytogenetic changes of AA,and analyzed their molecular relationship with MDS and their roles in disease transformation.The most common somatic change in AA is the loss of PIGA and HLA alleles,which,along with trisomy 8 and del(13q),is related to the immune pathogenesis of AA.Among the 5 most common mutations in AA,PIGA and BCOR/BCORL1 mutations are related to a good prognosis,while DNMT3A and ASXL1 mutations are likely associated with clonal evolution and a poor prognosis.The risk factors for secondary MDS after AA include SM and cytogenetic changes such as del(7q) associated with poor prognosis,prolonged disease duration after diagnosis,onset age of AA,and leukocyte telomere attrition.Although role of SM in disease progression remains unclear because of its dynamic change and unknown significance,prognostic assessment based on the monitoring of SM and clinical features may guide the treatment.

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and β diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and β diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.

Multiple myeloma is a hematologic tumor characterized by clonal proliferation of plasma cells.The development of novel agents and immunotherapy have substantially improved the prognosis of multiple myeloma,with an expectable median survival beyond ten years.Therefore,there is an urgent need to improve the management of this disease.Health management is effective in controlling chronic diseases and full-cycle management should be implemented from the early to the end stage of the disease.Implanting the full-cycle concept into the health management of multiple myeloma will guide and standardize the advances in this field.This review focuses on the full-cycle concept of multiple myeloma and the corresponding application of health management at each stage of the cycle.

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Alzheimer’s disease (AD) is a common neurodegenerative disease with the main manifestations of progressive cognitive dysfunction,behavioral disorders,and gradual decline of living ability.The etiology of AD is complex,and the pathogenesis of this disease remains controversial.Calcium signaling plays an important role in regulating neuronal activities,including neurotransmitter release,synaptic plasticity,memory storage,and neuronal apoptosis.Increasing studies have shown that neuronal calcium dyshomeostasis is a major pathological factor in the occurrence and development of AD.This article reviews the role and research progress in intracellular calcium dyshomeostasis in AD,including the relationship between calcium homeostasis and amyloid β,the role of calcium/calmodulin-dependent protein kinases in tau phosphorylation,calcium signaling pathways,the relationship between calcium homeostasis and mitochondrial function,autophagy,and neuroinflammation.

Extracellular signal-regulated kinase 1/2 (ERK1/2) is a serine/threoninekinase involved in the signal transduction cascade of Ras-Raf-mitogen-activated protein kinase (MEK)-ERK.It participates in the cell growth,proliferation and even invasion by regulating gene transcription and expression.The occurrence of a variety of diseases such as lung cancer,liver cancer,ovarian cancer,cervical cancer,endometriosis,and preeclampsia,as well the metastasis and disease progression,is closely associated with the regulation of cell invasion by ERK1/2 signaling pathway.Therefore,exploring the regulation of ERK1/2 signaling on cell invasion and its role in pathogenesis of diseases may help to develop more effective treatment schemes.This article introduces recent progress in the regulation of ERK1/2 signaling on cell invasion and the role of such regulation in diseases,with a view to give new insights into the clinical treatment of ERK 1/2-related diseases.

The breast cancer diagnosed in the women at or above age 70 is defined as breast cancer in the elderly.As the population keeps aging,breast cancer in the elderly presents increasing incidence and high mortality.Early detection,early diagnosis,and early treatment might improve the prognosis of these patients. Comprehensively evaluating the functional age of elderly patients is essential for the individualized treatment. Medical imaging plays a key role in the screening,early diagnosis,therapy selection,evaluation of neoadjuvant therapy efficacy,and postoperative follow-up.We reviewed the current literature and focused on the role of medical imaging in the diagnosis and treatment recommendations for breast cancer in the elderly.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation and ulcer formation in the intestinal mucosa.Its pathogenesis involves immune dysfunction,dysbiosis of gut microbiota,and mucosal damage caused by inflammation.Ferroptosis is an iron-dependent form of cell death regulated by disturbances in iron metabolism,lipid peroxidation,and depletion of glutathione (GSH).Studies have indicated that ferroptosis plays a crucial role in the pathogenesis of UC,particularly in regulating inflammatory responses and damaging intestinal epithelial cells.This article reviews the regulatory mechanisms and roles of ferroptosis in UC and discusses the potential therapeutic strategies to alleviate UC symptoms by modulating iron metabolism,reducing lipid peroxidation,and maintaining GSH levels,providing new targets and directions for the diagnosis and treatment of UC.

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Circular RNA (circRNA) is a special group of non-coding RNA.Unlike linear RNA,circRNA is a closed circular structure formed by reverse splicing of pre-mRNA,with highly stable expression and wide distribution in eukaryotes.CircRNA has multiple functions by acting as microRNA sponges or binding with RNA-binding proteins.They can be used as biomarkers for many diseases.The latest research shows that circRNA plays a role in the pathogenesis of diabetes mellitus and the related chronic complications.In this review,we summarized the current progress and underlying mechanisms of circRNA in diabetes mellitus and the related complications.

Objective To investigate the pathogen distribution,imaging characteristics,and risk factors of pulmonary infection with multi-drug resistant organism (MDRO) in patients with severe craniocerebral injury,and establish and verify the risk prediction model. Methods A total of 230 patients with severe craniocerebral injury complicated with pulmonary infection were collected retrospectively.According to the 7∶3 ratio,they were randomly assigned into a modeling group (161 patients) and a validation group (69 patients).The risk factors of MDRO pulmonary infection were predicted with the data of the modeling group for the establishment of the risk prediction model.The data of the validation group was used to validate the performance of the model. Results Among the 230 patients,68 patients developed MDRO pulmonary infection.The isolated drug-resistant bacteria mainly included multi-drug resistant Acinetobacter baumannii,multi-drug resistant Klebsiella pneumoniae,multi-drug resistant Pseudomonas aeruginosa,and methicillin-resistant Staphylococcus aureus,which accounted for 45.21%,23.29%,16.44%,and 15.07%,respectively.The imaging characteristics included pleural effusion,lung consolidation,and ground-glass shadow,which accounted for 72.06%,63.24%,and 45.59%,respectively.Multivariate Logistic regression analysis showed that the independent risk factors for MDRO pulmonary infection included age ≥60 years (P=0.003),history of diabetes (P=0.021),history of chronic obstructive pulmonary disease (P=0.038),mechanical ventilation ≥7 d (P=0.001),transfer from other hospitals (P=0.008),and coma (P=0.002).A risk scoring model was established with the β value (rounded to the nearest integer) corresponding to each index in the regression equation.Specifically,the β values of age ≥60 years,history of diabetes,history of chronic obstructive pulmonary disease,mechanical ventilation ≥7 d,transfer from other hospitals,and coma were 1,1,1,2,2,and 1,respectively (value ≥4 indicated a high-risk population).The areas under the receiver operating characteristic curve of the modeling group and validation group were 0.845 and 0.809,respectively. Conclusions Multi-drug resistant Acinetobacter baumannii is the most common pathogen of MDRO pulmonary infection in patients with severe craniocerebral injury.Pleural effusion,lung consolidation,and ground-glass shadow were the most common imaging characteristics.The established risk model has high discriminant validity in both the modeling group and the validation group.

The incidence of obstructive sleep apnea (OSA) is higher in pregnancy than in non-pregnancy,and obesity is a major risk factor.OSA in pregnancy can lead to multiple organ dysfunction and is associated with hypertensive disorders in pregnancy,gestational diabetes mellitus,premature birth,and fetal growth restriction. Therefore,early screening and diagnosis are essential for the prevention and treatment of OSA in pregnancy.

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAF^V600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAF^V600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAF^V600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ²=0.259,P=0.611),and location of nodules(χ²=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ²=14.693,P<0.001),composition(χ²=17.075,P<0.001),aspect ratio ≥1(χ²=9.477,P=0.002),and microcalcification(χ²=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAF^V600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ²=37.923,P<0.001;χ²=40.462,P<0.001)and accuracy(χ²=81.595,P<0.001;χ²=76.912,P<0.001),while C-TIRADS had the highest specificity(χ²=11.746,P<0.001;χ²=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAF^V600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAF^V600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAF^V600E mutation increased the diagnostic accuracy of BRAF^V600E mutation(χ²=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAF^V600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAF^V600E mutation showed the highest sensitivity(χ²=4.712,P=0.030;χ²=4.712,P=0.030),while C-TIRADS combined with BRAF^V600E mutation showed the highest accuracy(χ²=77.627,P<0.001;χ²=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAF^V600E mutation can improve the diagnostic efficacy of BRAF^V600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.