非器质性呼吸困难是指患者有突出的呼吸困难主诉、但经过系统检查找不出器质性病理改变的一种疾患，国际上称之为“医学无法解释的呼吸困难”。这类患者大约占呼吸困难患者的14%，但临床上常被忽视，诊断、治疗均很困难。本文详细介绍了该疾患的诊断和治疗方法。

ABSTRACT:Objective To determine the relative resistance to HIV-1 infection of CD4+ T lymphocytes in HIV-exposed seronegative individuals (ESNs）in China. Methods HIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4+ T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4+ T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks. Results For M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P＜0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups（P＞0.05). Conclusion CD4+ T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.

Objective To establish type 2 diabetes mellitus(T2DM)KM mouse models via the combined use of high-calorie diet and multiple administration of low-dose streptozotocin(STZ). Methods Based on the randomized number table,30 KM mice were equally and randomly divided into 2 groups:modeling group and control group. Mice in the modeling group were given foods with high calories for one month and injected with 30 mg/kg STZ via the left lower abdominal cavity for 2-4 consecutive days,while mice in the control group were fed with standard maintenance foods and the same dose of citrate buffer solution. The general conditions including food and water intake and mice weight were recorded. Blood glucose level was measured 1,2,4,5,12,and 21 weeks after STZ injection. When the glucose level became stabilized,the serum insulin and blood lipids [including total cholesterol(TC),triacylglycerol(TG),high-density lipoprotein(HDL) and low-density lipoprotein(LDL)],and hemoglobin a1c (HbA1c)were measured,and oral glucose tolerance test were performed. Results The modeling group had a 100% survival rate. After STZ injection,the body weight of mice in the modeling group reached the peak in the forth week,and later the growth rate decreased,still significantly lower than that of control group mice till the 21^st week(t=3.160,P=0.006). Their blood glucose level was significantly higher than that of mice before STZ injection and in the control group(all P<0.05);as time went on,it was also rising,and it remained high till the 21^st week [(26.38±1.34)mmol/L]. In the 4^th week,the fasting blood glucose of mice in the modeling group was(11.86±3.33)mmol/L,which was significantly higher than that of mice in the control group [(6.37±1.27)mmol/L](t=-3.830,P=0.002). Fasting serum insulin of mice in the modeling group showed no significant difference compared with control group [(5.73±0.24)mU/L vs.(5.48±0.32)mU/L;t=-0.863,P=0.416]. Insulin sensitivity index was 0.0145±0.0039,which was significantly lower than that(0.0267±0.0039)in control group(t=4.414,P=0.003). In the 6^th week,the blood glucose levels of mice in the modeling group were(15.35±1.82),(26.45±1.07),(25.58±1.46),and(26.15±1.00)mmol/L 0,30,60,and 120 min after oral gavage of D-glucose,which were all significantly higher than those in the control group [(6.88±1.75)(t=-8.203,P=0.000),(17.65±2.94)(t=-6.884,P=0.000),(13.18±2.04)(t=-12.110,P=0.000),and(7.37±3.40)mmol/L(t=-12.969,P=0.000)]. In the 8^th week,serum TC and TG levels of mice in the modeling group were(3.83±0.06)and(2.20±0.20)mmol/L,which were significantly higher than those in the control group [(3.10±0.10)(t=11.000,P=0.000)and(0.90±0.10)mmol/L(t=10.070,P=0.000)]. HDL level of mice in the modeling group was(2.03±0.06)mmol/L,which was significantly lower than that in the control group [(2.48±0.02)mmol/L;t=11.662,P=0.000]. LDL level was increased but showed no significant difference [(0.34±0.08)mmol/L vs.(0.26±0.02)mmol/L](t=1.680,P=0.168). HbA1c content of mice in the modeling group was(7.30±0.31)%,which was significantly higher than that(4.40±0.32)% in the control group(t=-11.587,P=0.000). Conclusion KM mice models of T2DM were successfully established after high-calorie diet and multiple administration of low-dose STZ.

ABSTRACT:The silent information regulator protein 2 (Sir2) and its homologues play an important role in the regulation of cellular physiological processes such as survival,apoptosis, and aging. SIRT1, the mammalian Sir 2 homologue, has been shown to deacetylate a wide range of non-histone substrates and histone substrates. It has been constantly reported that SIRT1 may be associated with the occurrence of metabolic syndrome, genomic homeostasis, tumors, and neurodegenerative diseases. Calorie restriction may mitigate many major diseases in rodent models by SIRT1-mediated deacetylase activity and prolong the life expectancies in these animals. Therefore, SIRT1 may be emphasized as a new therapy target for many different diseases.

Diabetic nephropathy is one of the most common microvascular complications of diabetes mellitus. With an increasing prevalence, its proportion in end-stage renal diseases is ascending. Research on the mechanism of diabetic nephropathy was initially focused on the mesangial matrix and glomerular basement membrane. In recent years, changes in the structure and functions of glomerular filtration barriers, especially podocyte injury, has became new hotspots. Podocyte injury involves the decreases in the density and amount of podocytes, the hypertrophy and degeneration of podocytes, and foot-process effacement, along with changes in some specific protein structure and functions. It is the result of multiple factors and multiple pathways. This articles summarizes the common features of podocyte injury and its role in the development of diabetic nephropathy.

ABSTRACT:Metabonomics (or metabolomics) aims at the comprehensive and quantitative analysis of the wide arrays of metabolites in biological samples. Metabonomics has been labeled as one of the new "-omics" joining genomics, transcriptomics, and proteomics as a science employed toward the understanding of global systems biology. It has been widely applied in many research areas including drug toxicology, biomarker discovery, functional genomics, and molecular pathology etc. The comprehensive analysis of the metabonome is particularly challenging due to the diverse chemical natures of metabolites. Metabonomics investigations require special approaches for sample preparation, data-rich analytical chemical measurements, and information mining. The outputs from a metabonomics study allow sample classification, biomarker discovery, and interpretation of the reasons for classification information. This review focuses on the currently new advances in various technical platforms of metabonomics and its applications in drug discovery and development, disease biomarker identification, plant and microbe related fields.

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.

ObjectiveTo compare the image quality of T1WI fat phase,T1WI water phase,short time inversion recovery(STIR) sequence,and diffusion weighted imaging(DWI) sequence in the evaluation of multiple myeloma(MM). MethodsTotally 20MM patients were enrolled in this study. All patients underwent scanning at coronal T1WI fat phase,coronal T1WI water phase,coronal STIR sequence,and axial DWI sequence. The image quality of the four different sequences was evaluated. The image was divided into seven sections(head and neck,chest,abdomen,pelvis,thigh,leg,and foot),and the signal-to-noise ratio(SNR)of each section was measured at 7 segments(skull,spine,pelvis,humerus,femur,tibia and fibula and ribs)were measured. In addition,20 active MM lesions were selected,and the contrast-to-noise ratio(CNR)of each scan sequence was calculated. ResultsThe average image quality scores of T1WI fat phase,T1WI water phase,STIR sequence,and DWI sequence were 4.19±0.70,4.16±0.73,3.89±0.70,and 3.76±0.68,respectively. The image quality at T1-fat phase and T1-water phase were significantly higher than those at STIR(P=0.000 and P=0.001)and DWI sequence(both P=0.000);however,there was no significant difference between T1-fat and T1-water phase(P=0.723)and between STIR and DWI sequence(P=0.167). The SNR of T1WI fat phase was significantly higher than those of the other three sequences(all P=0.000),and there was no significant difference among the other three sequences(all P>0.05). Although the CNR of DWI sequences was slightly higher than those of the other three sequences,there was no significant difference among all of them(all P>0.05). ConclusionImaging at T1WI fat phase,T1WI water phase,STIR sequence,and DWI sequence has certain advantages,and they should be combined in the diagnosis of MM.

ABSTRACT:Objective To develop a new injectable biomaterial carrageenan/nano-hydroxyapatite/collagen (nHAC/Carr) for bone surgery and characterize it. Methods nHAC/Carr was developed by filling carrageenan with nano-hydroxyapatite/collagen (nHAC) granules. Results It was found that nHAC/Carr had similar X-ray diffraction patterns with that of nHAC. Fourier transform infrared spectroscopy showed that carrageenan did not change its structure in nHAC/Carr. The rheological behavior of nHAC/Carr was the same as carrageenan. The scanning electron microscopy and porosity analysis showed that nHAC/Carr had porous structure and its porosity was about 90%. Conclusion The biomaterial nHAC/Carr may be used as an injectable bone substitute.

Hyponatremia is relatively common in patients with neurologic diorders, while its diagnosis and treatment remain controversial. Osmotic demyelination syndrome (ODS) has shown to be closely associated with hyponatremia. ODS patients often present as central pontine myelinolysis, extrapontine myelinolysis, or both. This article reviews the clinical manifestations, pathogenesis, and risk factors of ODS in patients with hyponatremia caused by neurologic disorders.

ABSTRACT:With the rapid development of human genome project, increased genetic and population-based association studies are focused on the identification of the underlying susceptibility genes and contributions from gene-environment interaction to common complex diseases. Whole-genome association study with high-density single nucleotide polymorphisms is one of the most important milestones in that process. However, problems still exist in study design, data processing, and results interpretation. Large-scale cohort study or population-based case-control design with sufficient statistical power, new approaches to assess the gene-gene and gene-environment interactions, as guarantee of the consistency and replicability of these researches are crucial in the exploration of the causes of these common complex diseases.

ABSTRACT:Objective To investigate the effects of oxidative stress on the expression of endothelial-leukocyte adhesion molecule-1 (ELAM-1) in porcine trabecular meshwork cells and to elucidate the relationship between the expression of ELAM-1 and IL-1α. Methods Primary cultured porcine trabecular meshwork cells were cultured without serum and treated with 1 mmol/L H2O2 with or without pretreatment of IL-1rα of different concentrations. The expression of ELAM-1 was tested by immunocytochemistry. Results ELAM-1 immunocytochemistry staining was positive in the H2O2-treated porcine trabecular meshwork cells. It was negative in the porcine trabecular meshwork cells pretreated with IL-1rα of high concentrations (180 μg/ml and 600 μg/ml). Conclusions Oxidative stress can induce the expression of ELAM-1 in porcine trabecular meshwork cells. In the in vitro cell system, IL-1rα of high concentration can inhibit the expression of ELAM-1 induced by oxidative stress.

Recombinant human growth hormone is generally safe in treating children with growth hormone deficiency and idiopathic short stature. However, side effects such as sodium and water retention, benign intracranial hypertension, insulin insensitivity, increasing risk of secondary neoplasm, scoliosis, and slipped capital femoral epiphysis may occur occasionally, although the overall incidence remains low.

Pooled literatures showed that the induced abortion in China faces many problems: the number of induced abortion remains large; most cases are young and nulliparity women; the frequency of abortion is high; and the interval between one and another abortion is short. Health promotion strategies should be applied to address these problems. It is important to increase the populations awareness of contraception, especially among nulliparity and migrant populations. Routine and effective contraceptive methods should be recommended and emphasized during induced abortion and delivery to lower the rate of induced abortion.

Objective To observe the effects of 630 nm red light and 460 nm blue light emitting diode irradiation on the healing of skin wounds in Japanese big-ear white rabbits. Methods The skin wound model was established with 8 Japanese big-ear white rabbits. Three parts of vulnus in each rabbit were used:two parts of vulnus were irradiated vertically by red and blue LED light,respectively(15 min/time),and the distance between lights and wounds was 15 cm;the 3^rd part of the wound was used as a control. On the 21^st day of the wounds exposure to light,the number of healing wounds and the percentage of healing area were recorded and the treatment effect of these two light sources was compared. HE staining was used to analyze the newborn tissue structure. Masson staining was used to observe the proliferation of skin collagen fibers. Immuohistochemical staining was used to analyze fibroblast growth factor(FGF),epidermal growth factor(EGF),endothelial growth factor(CD31),proliferating cell nuclear antigen(Ki-67),and inflammatory cytokines(CD68)infiltration in the skin. Results The healing rate in the red light,blue light,and control groups was 50.0%(4/8),25.0%(2/8),and 12.5%(1/8),respectively. Since the 12^th day after modeling,the healing area percentage in the red light group was significantly higher than those in the blue light and control groups(P<0.05,P<0.01). On the 21^st day after modeling,the skin thickness of the red light group was(2.95±0.34)mm,which was significantly higher than that in control group [(2.52±0.42)mm;F=3.182,P=0.016)]. The average optical density of collagen fibers was 0.15±0.03 in red light group,which was significantly higher than that of the blue light group(0.09±0.01;F=7.316,P=0.012)and control(0.07±0.01;F=7.316,P=0.003). The results of immunohistochemistry showed the expression levels of EGF,FGF,CD31 antigen,and Ki-67 in the red light group were significantly higher than those in the blue light and control groups,whereas the CD68 expression was significantly lower(P<0.05 or P<0.01). Conclusion LED red light irradiation can promote the healing of skin wounds in Japanese big-ear white rabbits,which may be achieved by the effect of red light irradiation in stimulating the proliferation of skin epidermal cells,vascular endothelial cells,and fiberous tissue.

Objective To investigate the effect of human hepatocellular carcinoma HepG2 cell-derived Exosome on the differentiation of mesenchymal stem cells(MSC)into cancer-associated myofibroblasts(CAF)and the impacts of CAF on liver cancer cell proliferation,migration,and invasion. Methods The protein expression of HepG2 cell-derived Exosome was detected by Western blotting. MSCs were separated from human adipose tissue and cultured with HepG2 cell-derived Exosome(100 ng/nl)to initiate differentiation. The expressions of mesenchymal markers and several interleukins were also detected by Western blotting. HepG2 cells were co-cultured with the conditioned media(CM),in which HepG2 Exosome induced the differentiation of MSC into CAF. The expressions of epithelial and mesenchymal markers were detected by real-time polymerase chain reaction(PCR)and Western blotting. Cell proliferation was assessed using MTS assay. Transwell chambers were used in the in vitro migration and invasion assay. Results HepG2 cell-derived particles expressed CD63,70 kilodalton heat shock proteins,and 90 kilodalton heat shock proteins. With the treatment of HepG2 cell-derived Exosome,the expressions of mesenchymal marker α-smooth muscle actin,fibroblast activation protein α,interleukin(IL)-6,IL-8,and IL-1β were up-regulated,while vascular endothelial growth factor had no significant change. The conditioned media which HepG2 Exosome induced MSC differentiation CAF(CAF-CM)could significantly promote HepG2 cells proliferation(1.075±0.104),compared to BSA control(0.874±0.066,P=0.023)and MSC-CM(0.649±0.034,P=0.0005). CAF-CM could significantly enhance cell migration [(42.5±9.1) cells vs.(18.5±3.1) cells,P=0.001] and invasion [(29.0±3.5) cells vs.(13.1±3.7) cells,P=0.009] compared to its control group. Moreover the conditioned medium which HepG2 Exosome induced MSC to differentiate into CAF could also promote the expressions of mesenchyme-related genes Smad interacting protein 1(P=0.040),β-catenin(P=0.038),fibronectin(P=0.029),and Vimentin(P=0.013)and inhibit the expression of epithelial related genes zonula ocdudens-1(P=0.010).Conclusions Exosome extracted from HepG2 cells can induce human adipose-derived MSC to differentiate into cancer-associated myofibroblasts. CAF-like cells can promote the migration of the liver cancer cell line HepG2.

ABSTRACT:Nanobiological technology is an important research field in nanotechnology and has extensive applications in medicine. Although initiated lately, application of nanobiological technology in medicine is advancing in good pace in China, mainly involves in fields including nano-scale pharmaceutical carrier, nano-scale diagnostic technology, nanobiomaterials, and nano-scale traditional Chinese medicine.

ABSTRACT:The immunoregulatory effects of mescenchymal stem cell (MSC) and its application have become a hot research topic in recent years. This article reviews the up-to-dated research advances in the features and mechanisms of immune regulation of MSC and its application.

Alzheimer’s disease(AD)is a central nervous system disease characterized by progressive cognitive dysfunction and memory loss.Increasing evidences suggest that β amyloid(Aβ)plays a critical role and may be a upstream molecule in AD pathogenesis involving both genetic and environmental factors.Aβ accumulation and its related inflammation are considered early events preceding neurodegeneration and neuronal loss in AD brain.However,all strategies and compounds targeting Aβ deposition have failed in clinical trials,implying complexity of AD pathogenesis.This article reviews Aβ hypothesis and its related mechanisms,pathophysiological process,and therapeutics of AD.

ObjectiveTo establish a chronic restraint stress(CRS)model of depression,using C57BL/6J mice. MethodsTotally 20 C57BL/6J mice were screened by weight,sucrose preference,and the results of open-field test. Then,they were equally randomized into two groups:normal control(NC)group and CRS group. Mice in the CRS group were under restraint 4 hours a day and their behavioral changes were evaluated after 21 days. ResultsThe immobility time was significantly longer in CRS mice[(131.70±21.65) s] compared with controls[(68.88±8.43) s](P=0.0304). CRS mice showed a significant decrease in sucrose preference during the time 0-24 h [(66.21±3.24)% vs.(79.46±3.85)%,P=0.0196] and 0-48 h [(73.25±1.50)% vs.(80.20±2.26)%,P=0.0248]compared with controls. ConclusionThe C57BL/6J mice CRS models of depression were successfully established.

Objective To explore a simple and feasible technique to locate proteins during spermatogenesis. Methods Various germ cells and somatic cells were separated by collagenase I and DNase I after the albuginea was removed. The cells were then smeared, dyed, and observed directly under fluorescence and confocal microscopy. Results Germ cells at different steps were successfully identified by specific dyestuffs for acrosome and nucleolus. Conclusion A simple method for locating proteins during permatogenesis was successfully developed.

ABSTRACT:Objective To evaluate the value of high-risk HPV (hrHPV) detection by Hybrid Capture Ⅱ (HC2) in screening cervical intraepithelial neoplasm （CIN）. Methods Totally 723 patients who had received a dual screening with thinprep cytologic test (TCT) and HC2 in our department were analyzed retrospectively. Among them, 350 patients received a triple examination with TCT, HC2, and colposcopic biopsy. Results Among the 723 patients，the incidences of hrHPV infection with atypical squamous cell (ASC), low squamous intraepithelial lesion, and high squamous intraepithelial lesion were 70.7%（94/133）, 88.9%（249/280）, and 90.9%（90/99）, respectively, significantly higher than 55.5%(117/211), the incidence of hrHPV infection with normal cytological results （P=0.005,P＜0.001，P＜0.001, respectively）. Among 350 cases who were received triple examination，the incidence of hrHPV infection with cervical intraepithelial neoplasia (CIN) 1 and CIN 2 were 88.9%（72/81）and 96.3%（52/54）, significantly higher than 77.7%（153/197）, the incidence of hrHPV infection with normal pathological results （P=0.03,P=0.002）；The incidence of hrHPV infection with CIN 3 and squamous cancer were 91.7%（11/12） and 100.0%（6/6）,also higher than normal cases. Among these 350 cases, the incidence of hrHPV infection with ASC was 79.3%（69/87）. The incidence of CIN 2-3 with ASC and hrHPV infection was 38.0%，significantly higher than the incidence of CIN 2-3 with ASC and without hrHPV infection (5.9%)(P =0.04）. Conclusion hrHPV infection has a close relation with CIN, and the incidence of hrHPV infection increases along with the severity of CIN.

ABSTRACT:Liposomes and nanoparticles have been used as drug carriers to increase solubility, prolong drug duration in vivo, target drug delivery, reduce toxicity and combat multi-drug resistance. With major advances in the preparation techniques, preparation material, and surface modifiers in recent years, liposomes and nanoparticles delivery systems have achieved success in fields including cancer therapy, overcoming biolo- gical barriers, and biological drugs and vaccine carriage.

ABSTRACT:Objective To investigate the methods of culturing and identifying mouse myeloid semimature dendritic cell(smDC) in vitro. Methods Myeloid monocytes derived from 6-week-old C57BL/6 mice were cultured in RPMI-1640 medium containing 10％ fetal bovine serum, 2 ng/ml recombinant murine granulocyte macrophage-colony stimulating factor (GM-CSF), and 20 ng/ml recombinant murine interleukin (IL)-4 for 9 days. Then cells were incubated with 40 ng/ml tumor necrosis factor-α (TNF-α) for 24 hours to obtain smDC. Meanwhile, smDC was differentiated into mature dendritic cell (mDC) or immature dendritic cell (iDC) by treatment with 1μg/ml lipopolysaccharide (LPS) or without LPS. The morphological features of smDC were assayed by inverted microscopy and scanning electron microscopy. Surface markers such as CD11c, CD40, CD80, CD86, and MHC-Ⅱ were tested by flow cytometry. IL-1β, IL-6, IL-12, and IL-10 in the supernatant were tested by ELISA. The activation of allogene lymphocyte (BALB/c mice) stimulated by C57BL/6 myeloid smDC in mixed lymphocyte reaction was examined by Cell Counting Kit-8 in vitro. Results The shape of smDC was round or oval-shaped, and the diameter of smDC was about 15μm. The length of smDC dendrite was between 5 to 10μm. smDC, iDC, and mDC all expressed high level of CD11c. The expressions of MHC-Ⅱ, CD40, CD80, and CD86 on smDC were higher than those of iDC and lower than those of mDC. IL-1β, IL-6, and IL-12 secretion of smDC was significantly lower than that of mDC (P<0.01), and IL-12 was significantly lower than that of iDC (P<0.05), while no significant difference of IL-1β and IL-6 secretion was found between smDC and iDC (P>0.05). Furthermore, IL-10 secretion was not significantly different among these three kinds of DCs (P>0.05). The effect of allogene lymphocytes activation on smDC was significantly lower than that of mDC and positive control(P<0.01), but had no significant difference when compared with that of iDC and negative control(P>0.05). Conclusions smDC may be a relatively independent dendritic cell sub-population in terms of function and morphology. It is a feasible way to induce myeloid monocytes to differentiate into smDC using GM-CSF, IL-4, and TNF-α in vitro.

ABSTRACT:Liver X receptors (LXRs) are members of the nuclear receptor superfamily and are activated by oxysterols and intermediates in the cholesterol synthetic pathway. The pivotal role of LXRs in the metabolic conversion of cholesterol to bile acids has been well established. Furthermore, insulin induces LXRα in hepatocytes, resulting in the suppression of key enzymes in gluconeogenesis, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase（FBPase). LXRs also play an important role in fatty acid metabolism by activating the sterol regulatory element-bing protein 1c gene (SREBP1c). This articles reviews the molecular mechanisms by which LXRs act to influence the lipid and carbohydrate metabolism.

ABSTRACT：Objective To evaluate the clinical value of assessment of coronary stent patency by 64-slice spiral CT coronary angiography. Methods Totally 29 patients (59 stents) were investigated using a retrospective ECG-gated enhanced scan by 64-slice spiral CT at a mean interval of (28.4±21.2) months after coronary stent implantation. Axial multi-planar reconstruction (MPR) of the stents and curved-planar reconstruction (CPR) through the stents were evaluated for image quality on a 5-point scale (1=excellent,5=uninterpretable) and lumen diameter. Stent lumen diameter was compared with the vessel diameter proximal of the stents to assess the in-stent lumen visibility. Conventional coronary angiography was performed in 5 patients,and 9 stents were evaluated. Results The image quality was good to excellent on average (scores:1.94±0.84),depending on heart rate,breath movement,and stent location. Stent lumen was visible,on average a percentage off (76.1±11.1)% of the lumen diameter. All the 9 stents were correctly detected as being patent,which was confirmed by conventional coronary angiography. Conclusion 64-slice spiral CT is a useful tool to assess the coronary stent patency.

Bone marrow mesenchymal stem cells (MSCs) are somatic stem cells that can differentiate into progenies of multiple lineages. They play an important role in hematopoiesis and stem cell therapy due to their multi-lineage potentials and immunomodulatory properties. Oxidative stress is a disturbed redox state caused by accumulation of reactive oxygen species. It can induce the senescence and apoptosis of MSCs via phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and p53 pathways, and inhibit the proliferation and differentiation of MSCs through apurinic/apyrimidinic endonuclease/redox factor 1 (APE/REF-1) and extracellular signal-regulated kinase (ERK) pathways. Furthermore，using anti-stress medication and hypoxic preconditioning, the functions of MSCs can be further enhanced. Accordingly, further studies on the effect of oxidative stress on MSCs and its signaling pathways may be meaningful for the treatment of hematologic diseases and for improving stem cell therapy.

Objective To explore the grey matter volume(GMV)changes in neuromyelitis optica(NMO)patients using a voxel-based morphometry method. Methods Whole brain structural images were acquired in 16 NMO patients and 16 gender-and age-matched healthy controls. Comparison of GMV between the two groups was analyzed by VBM8 toolbox of statistical parametric mapping 8. Result Compared with the controls,NMO patients showed decreased GMV in the frontal lobe,parietal lobe,temporal lobe,occipital lobe,limbic lobe,optic tract,caudate nucleus,thalamus,and cerebellum(all P<0.005). Conclusions Regional atrophy of grey matter is found in NMO patients. Voxel-based morphometry can reveal brain volume changes sensitively.

Objective To select the optimal culture media for the mass production of γδT cells used in adoptive immunotherapy. Methods Three different culture media (RPMI-1640, AIM-V, and OpTmizer, with or without autologous serum) were used to culture γδT cells. The survival rate, purity, proliferation efficiency, and biological functions of the expanded γδT cells were examined and compared. Results The survival rate of γδT cells expanded in RPMI-1640 decreased over culture time. The purities of γδT cells cultured in AIM-V or OpTmizer with or without serum were higher than those cultured in RPMI-1640. After two weeks of culture in the absence of serum, the purity and proliferation efficiency of γδT cells cultured in OpTmizer were significantly higher than those cultured in RPMI-1640 (P0.05). However, cells expanded in RPMI-1640 exhibited significantly weaker cytotoxicity against Daudi lymphoma cells than those expanded in OpTmizer (P<0.05) and AIM-V (P<0.05). Conclusion Due to low serum-dependence, high proliferation efficiency, and favorable biology function of expanded cells, OpTmizer is the most suitable medium for the mass production of γδT cells used in adoptive immunotherapy.

Objective To summarize the clinical features and analyze the serologic test results of latent syphilis. Methods The clinical data of 601 patients with latent syphilis who were treated in the sexually transmitted disease centre of Peking Union Medical College Hospital between January 2001 and November 2007 were retrospectively analyzed. Results Of the 601 cases of latent syphilis,there were 174 cases of early latent syphilis(EL),170 cases of late latent syphilis(LL),and 257 cases of unknown latent syphilis. Male to female ratio was 0.74:1（256 males and 345 females,respectively). Patients aged 20-39 years accounted for the largest proportion. Non-marital sexual intercourse was the main route of infection. Forty-six patients (7.65%) were co-infected with other sexually transmitted diseases. A total of 251 cases of latent syphilis (41.76%) were confirmed when the patients were receiving tests for other sexually transmitted diseases or suspected sexually transmitted diseases. Of the 601 patients with EL,LL and unknown latency,the proportion of serum rapid plasma reagin(RPR) titers higher than or equal to 8 were 72.99% (127/174),52.94% (90/170),and 60.31%(155/257),respectively. Compared with the early syphilis,serological negative conversion rate was significantly lower after treatment for l2 months in the early latent syphilis patients (P=0.044). Conclusion Education and awareness raising on syphilis should be strengthened to lower the prevalence of latent syphilis.

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions were analyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.

ABSTRACT:Itraconazole has been used to treat superficial candidal infections in China for 12 years with promising efficacy and safety. This article retrospectively reviewed literatures published in the mainstream journals in China with an attempt to find a reasonable therapy for Chinese populations.

Objective To explore the method of constructing tissue-engineered skin using melanocytes and bone marrow mesenchymal stem cells (BMSCs) in vivo. Methods Melanocytes were isolated from human foreskin. BMSCs were isolated from human bone marrow. Both of them were co-cultured at a ratio of 1∶10, and then were implanted into the collagen membrane to construct the tissue-engineered skin, which was applied for wound repair in nude mice. The effectiveness of wound repair and the distribution of melenocytes were evaluated by morphological observation, in vivo 4,6-diamidino-2-phenylindole, dihydrochloride (DAPI) fluorescent staining tracing, HE staining, S-100 immunohistochemistry, and transmission electron microscopy. Results The wounds were satisfactorily repaired among the nude mice. The melenocytes were distributed in the skin with normal structure, as confirmed by DAPI fluorescent staining tracing, HE staining, S-100 immunohistochemistry, and transmission electron microscopy.Conclusion Melanocytes and BMSCs, after proper in vitro culture at an appropriate ratio, can construct the tissue-engineered skin with I type collagen membrane."

Objective To study the effect of carboxyamidotriazole (CAI) on adjuvant arthritis (AA) in rats.Methods The rats were randomly divided into normal group,two vehicle groups (polyethylene glycol 400 control and normal sodium control group),CAI-treated groups (10,20,and 40 mg/kg) and positive control dexamethasone group. Freund’s completed adjuvant was used to induce AA in rats. The arthritis index (AI) was scored,and X-ray check of the hind limbs and histopathological examination were performed. The levels of tumor necrosis factor (TNF)-α,interleukin (IL)-1β,and IL-6 in the inflamed paw tissues were measured.Results The administration of CAI significantly decreased the AI,restored the body weights,and ameliorated the radiological and histopathological features of joint destruction in AA rats (P<0.05,P<0.01). In addition,CAI reduced the TNF-α,IL-1β,and IL-6 levels in the inflamed paw tissues (P<0.05,P<0.01).Conclusion CAI has therapeutic effect on AA rats,which may be achieved by decreasing the pro-inflammatory cytokines at the site of inflammation.

Objective To assess the patency and complications of the polytetrafluoroethylene (PTFE) graft for hemodialysis access and to summarize the experiences in the treatment of graft occlusions. Methods The clinical data of 30 patients who underwent forearm PTFE graft for hemodialysis access from March 2003 to December 2008 in our hospital were retrospectively analyzed. Results Patients were followed up for (28.7±17.6) months (range: 8-78 months).The peri-operative mortality was zero. Primary patency rate was 70.0% at Year 1 and 56.7% at Year 2. Accumulative secondary patency rate was 90.0% and 80.0%,respectively at Year 1 and Year 2. Postoperative complications included graft thrombosis (n=13,43.3%),venous anastomosis stenosis (n=1,3.3%),graft infection (n=2,6.7%),and edema of the forearm (n=10,33.3%). Totally 24 graft revisions were performed,including thrombectomy (12 times),thrombectomy and venous anastomosis plasty with artificial patch (4 times),arterial and venous anastomosis plasty with patch (2 times),venous anastomosis angioplasty with a balloon (2 times),new graft hemodialysis access construction in the contralateral arm (1 case),and graft removal (3 cases). Conclusions PTFE graft is an important backup hemodialysis access in urinemic patients. Proper revision according to different cause of graft occlusions can prolong the service time of the graft.

Objective To evaluate the efficacy of Ganoderma lucidum preparation on the behaviors,biochemistry,and autoimmunity parameters of mouse models of APP/PS-1 double transgenic Alzheimer’s disease(AD).Methods A total of 44 4-month-old APP/PS-1 double transgenic AD mice were randomly divided into AD model group,Aricept group,Ganoderma lucidum middle-dose(LZ-M)group,and Ganoderma lucidum high-dose(LZ-H)group,with 11 mice in each group.In addition,10 4-month-old C57BL/6 mice were used as the control group.Water maze test was conducted to observe the behavior changes,and the protein expressions in brain tissues were detected by Western blot analysis.The autoimmune indicators were detected by indirect immunofluorescence method.Results In the navigation experiment,the time of finding the platform was gradually shortened since the 2^nd day in the control,LZ-H,and LZ-M groups,and the time of searching the platform in the AD model group gradually increased.On the 5^th day,the time of finding platform was significantly shorter in control group (t=5.607,P=0.000) and LZ-H group(t=2.750,P=0.010)than AD model group.In the space exploration experiment,the number of crossing the target platform(t=2.452,P=0.025)and the residence time in the target quadrant(t=2.530,P=0.020)in AD model group mice was significantly smaller/shorter than those in control group;in addition,the number of crossing the target platform in the AD model group was significantly smaller than that in LZ-H group(t=2.317,P=0.030)and LZ-M group(t=2.443,P=0.030),while the residence time in target quadrant decreased significantly(t=2.770,P=0.020)compared with LZ-H group;the number of crossing through the target platform quadrant(t=2.493,P=0.022)and residence time in the target quadrant(t=2.683,P=0.015)in LZ-H group were significantly higher than in Aricept group.Western blot analysis showed that the expression of ApoA1 in the brain tissues of mice in LZ-H and LZ-M groups were significantly higher than those in AD model group(P<0.01,P<0.05);Aβ-40 expression in LZ-H group was significantly lower than that in AD model group(P<0.05);the expressions of Syt1,ApoE,and ABCA1 in brain tissues of mice in LZ-H group were significantly higher than those in model group(P<0.01,P<0.05).The plasma IgG level in Aricept group(t=30.945,P=0.000),LZ-M group(t=25.639,P=0.000)and LZ-H group(t=4.689,P=0.001)were significantly higher than that in the control group.Conclusion Ganoderma lucidum preparation can improve behavior disorders of AD model mice,promote the expressions of ApoA1,ApoE and Syt1,inhibit the expression of Aβ-40 protein,and improve the autoimmune function.

ABSTRACT:Objective To summarize the new knowledge of the anaplastic thyroid carcinoma (ATC）. Methods The clinical data of 58 patients (35 men,23 women, aged 28 to 79 years) with ATC that were treated with various therapeutic modalities from 1981 to 2005 were retrospectively analyzed. Among them, 25 patients received surgery alone (SA group) and 33 received surgery plus radiation (S+R group）. The dosage of postoperative radiotherapy was 40-70 Gy. Four patients received biopsy,24 received palliative surgery, and 30 received radical surgery. Only 2 patients received complete chemotherapy. Results ATC invaded trachea in 40 patients（69.0％）, esophagus in 32 patients （55.2％）,and carotid in 17 patients （29.3％）. The cervical lymph node metastases occurred in 19 patients （32.8％）. The overall 1-year survival rate was 37.8％，3-year survival rate 31.2％, and 5-year survival rate 25.9％. The 5-year survival rate was 37.8% in S+R group but was only 9.9％ in SA group (P=0.0000). The 5-year survival rate was 41.4％ in radical surgery subgroup but was only 12.4% in palliative surgery subgroup（P＝0.0023）. In ≤45-year-old subgroup(n=4), the 5-year survival rate was 50.0％; however, in ＞45-year-old subgroup, it was only 21.3％. In postoperative radiation ＜60 Gy subgroup , the 5-year survival rate was 19.3％; however, in ≥60 Gy group, it was 53.7％ (P=0.0000）. Among all the 58 patients, some patients received palliative surgery because of tumor invasion in trachea (n=16, 27.6％), esophagus (n=8, 13.8％), carotid (n=8, 13.8％), and other sites (n=13, 22.4%）. Twenty-four patients（61.5％） died of localrelapse, 2 （5.1％） of cervical lymphnode failure，9（23.1％） of metastasis, and 4 (10.3%) of other reasons. Conclusions The prognosis of ATC is poor. Radical surgery and postoperative radiation ≥60 Gy can improve the survival rate. Tumor invasion in trachea, esophagus, and carotid are the main reasons of palliative surgery. Local relapse is lethal.

ObjectiveTo evaluate the efficacy and toxicity of the combination chemotherapy of oxaliplatin with capecitabine(XELOX)in patients with advanced gastric cancer. MethodsThirty-eight advanced gastric cancer patients who received XELOX regimen during 2004-2009 were analyzed retrospectively. The combination chemotherapy included oxaliplatin as 2-hour infusion on day 1 and capecitabine po bid on days 1 to 14. Treatment was repeated every 3 weeks. ResultsXELOX regime was applied as first-line therapy in 34 patients and as second-line therapy in 4 patients. After three cycles of chemotherapy, the outcomes in 32 patients who received XELOX as the first-line therapy included partial response(n=8, 25.0％)，stable disease(n=14, 43.8％), and progressive disease(n=10, 31.2％); no patient achieved complete response. The median time to progression and overall survival time were 7.0 months(95% CI: 4.5-9.5 months)and 12 months(95% CI: 9.8-14.2 months), respectively. One-year and two-year survival rates were 40.6% and 23.7%, respectively. Grade 3-4 toxicities including neutropenia(10.5%), thrombocytopenia(2.6%), nausea(7.9%), and vomitting(5.3%)were noted in a few patients. ConclusionXELOX regimen can be effectively and safely applied as first-line treatment for advanced gastric cancer patients.

Objective To explore the effect of chlorogenic acid on disordered glucose and lipid metabolism in db/db mice and its mechanism. Methods Thirteen 5-6-week-old male db/db mice were randomly divided into db/db-CGA group (n=7) and db/db-CON group (n=6), and thirteen 5-6-week-old male db/m mice were randomly divided into db/m-CGA group (n=6) and db/m-CON group (n=7). Mice in the CGA groups were administrated with CGA 80 mg/(kg·d)by gavage, and mice in the CON groups were administrated with PBS in the same volume by gavage. Twelve weeks later, the level of biomedical parameters in plasma, liver, and skeletal muscle were determined, the concentrations of adiponectin and visfatin in visceral adipose, and the mRNA expression of glucose-6-phosphatase (G-6-Pase) and peroxisome proliferators-activated receptor-α (PPAR-α) as well as the protein level of PPAR-α in liver were detected. ResultsTwelve weeks after CGA administration, the levels of triglycerides in plasma, liver, and skeletal muscle and the fasting plasma glucose in db/db-CGA group were significantly lower than those in db/db-CON group(P<0.05). The muscle glycogen level was significantly higher than that in db/db-CON group (P<0.05), and the adiponectin concentration was significantly higher than that in db/db-CON group ( P<0.01) and lower than that in db/m-CGA group(P<0.05). The visfatin concentration in db/db-CGA group was significantly lower than that in db/db-CON group (P<0.01) and significantly higher than that in db/m-CGA group(P<0.05). The mRNA expression level of G-6-Pase was significantly down-regulated in db/db-CGA group when compared with db/db-CON group (P<0.05). Both the mRNA and the protein expression levels of PPAR-α were significantly up-regulated in db/db-CGA group(P<0.05) compared with in db/db-CON group. Conclusion CGA improves the disordered glucose/lipid metabolism in db/db mice, which is speculated to be related with its role in modulating the adipokines secretion, up-regulating hepatic PPAR-α, and inhibiting G-6-Pase expression.