G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans). Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test. Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20 μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism. Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.

AIM To study the chemical constituents and their anti-inflammatory activities of stems and leaves of Lonicera confusa DC.METHODS The 80%methanol extract from stems and leaves of L.confusa DC was isolated and purified by Diaion HP20SS,Sephadex LH-20,HSCCC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by measuring NO production of LPS-stimulated RAW264.7 cells in vitro.RESULTS Thirteen compounds were isolated and identified as benzyl alcohol-O-β-D-glucopyranosyl-(1 →6)-β-D-glucopyranoside(1),sweroside(2),epi-vogeloside(3),vogeloside(4),secologanoside(5),secoxyloganin(6),secologanin dimethyl acetal(7),methyl chlorogenate(8),apigenin-7-O-β-D-glucopyranoside(9),luteolin-7-O-β-D-glucopyranoside(10),rhoifolin(11),luteolin-7-O-α-L-arabinopyranosyl(1→6)-β-D-glucopyranoside(12),and lonicerin(13).Compounds 2-8,11-13 inhibited the NO production of LPS-induced cells.CONCLUSION Compound 1 is first isolated from family Lonicera,compounds 3,5,7,9,11,and 12 are obtained from the stems and leaves of this plant for the first time.Compounds 2-8,11-13 exhibited anti-inflammatory activities.

Objective:To explore the effects of dual task training assisted by a lower limb rehabilitation robot on lower extremity mobility and the walking ability of stroke survivors.Methods:Sixty-one stroke survivors were randomly divided into a control group and an experimental group with 30 in the control group and 31 in the experimental group. In addition to routine exercise training and physical therapy, both groups were given cognitive-motor dual task training 5 times a week for 3 weeks. But only in the experimental group was the dual task training assisted by a lower limb rehabilitation robot. Both groups′ lower limb motor function, walking ability, cognition, balance and ability in the activities of daily living were evaluated before and after the experiment using the Fugl-Meyer lower extremity assessment (FMA-LE), functional ambulation categories (FAC), the digital span test (DST), the Berg Balance Scale (BBS) and the Modified Barthel Index (MBI). Additionally, 6 survivors of a right hemisphere stroke from the experimental group received cognitive-motor dual task training both with and without the robotic assistance alternately. Near-infrared functional brain imaging was applied before and after the intervention, and the functional network connectivity of the resting brains was analyzed.Results:After the intervention the average FMA-LE, FAC, BBS and MBI scores had improved in both groups, with the improvement in the experimental group significantly better than in the control group on average. In terms of cognition there was no significant difference in the DST forward and backward assessment results between the two groups. The analysis of brain network functional connectivity showed that the intensity of functional connectivity between the left prefrontal cortex (PFC) and the left premotor cortex and supplementary motor cortex (PMC/SMA) increased significantly more, on average, after training assisted by the robot.Conclusion:Dual task training with the assistance of a lower limb rehabilitation robot can effectively improve the lower limb motor function, walking, balance and ability in the activities of daily living of stroke survivors. Enhanced functional connection of the PFC and the PMC/SMA in the healthy hemisphere induced by the robot may be the cause.

Objective To construct a novel enzyme-free colorimetric biosensor(T-CHA)based on tri-ple-helix molecular probe(THMP)and catalytic hairpin assembly(CHA)reaction for visual detection and precise quantitative analysis of low-abundance alpha-fetoprotein(AFP).Methods The absorbance produced by AFP induced T-CHA system was recorded by gel electrophoresis and ultraviolet-visible spectrophotometer to evaluate the feasibility of T-CHA strategy.The molar concentration ratio of THMP and CHA,reaction time of CHA,temperature and pH value of buffer solution were optimized respectively.The color reaction of T-CHA was induced by different concentrations of AFP to explore the detection efficiency of T-CHA.Results Under the op-timal experimental conditions,the logarithmic values of AFP at different concentrations showed a linear rela-tionship from 5 μg/mL to 10 ng/mL,and the detection limit was 2.29 μg/mL.The T-CHA system could com-plete accurate quantitative analysis of low abundance AFP and visual free-labeled detection within 105 min,moreover the sensitivity of T-CHA was superior to that of ELISA.Conclusion Utilizing the low background leakage of THMP and the high catalytic efficiency of CHA,the T-CHA system could realize the early accurate diagnosis of hepatocellular carcinoma,moreover which has a certain application prospect in the real time detec-tion.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To describe the current situation of mental health service utilization of community pa-tients with five mental disorders in Inner Mongolia Autonomous Region and provide reference for health education and formulating relevant policies.Methods:The multistage stratified sampling method with unequal probability was used to select a total of 12 315 community residents aged 18 and over in Inner Mongolia Autonomous Region.Using Composite International Diagnostic Interview,mood disorders,anxiety disorders,substance use disorders,intermit-tent explosive disorders,and eating disorders,and health service utilization were investigated.Descriptive statistics was completed by single factor analysis method.Results:The lifetime rates of consultation and treatment of any mental disorder were 18.7％and 10.2％,respectively.The highest proportion of patients received treatment by non-medical professionals was 31.4％,followed by psychiatrists in psychiatric hospital or psychologists in general hospitals.Among the patients,1.1％of them received medication,and 2.5％received psychotherapy.Conclusion:The utilization rate of mental health services in community patients with five mental disorders is relatively low.It is necessary to conduct health education for medical help seeking properly.

Objective To investigate the incidence,risk factors,treatment outcomes,and other clinical outcomes of checkpoint inhibitor-related pneumonitis(CIP)in cancer patients treated with PD-1/PD-L1 inhibitors.Methods Clinical data of 1 084 cancer patients who received treatment with PD-1/PD-L1 inhibitors from 2019 to 2021 in Department of Oncology of the Second Affiliated Hospital of Army Medical University were collected and then retrospectively analyzed.The patients were divided into a non-CIP group(998 cases)and a CIP group(86 cases),and those from the latter group were further divided into G1～G4 grades,of which G1～G2 grades were classified as low-grade CIP subgroup(69 cases)and G3～G4 grades as high-grade CIP subgroup(17 cases).Chi-square test,binary logistic regression and Kaplan-Meier survival analysis were used to summarize the incidence,risk factors,treatment outcome of CIP and its relationship with immune efficacy and progression-free survival(PFS).Results The incidence of CIP was 7.93％(86/1 084)in the cohort,the rate of high-grade CIP was 1.57％(17/1 084),and the rate of mortality was 0.09％(1/1 084).Binary logistic regression analysis showed that history of chronic obstructive pulmonary disease(COPD,OR=3.018,P=0.036)and history of chest radiotherapy(OR=2.605,P＜0.001)were independent risk factors for CIP.The patients with an age of ≥ 65 years had an obviously higher incidence of high-grade CIP than those with younger age(P=0.021).There were no statistical differences in objective remission rate(ORR),disease control rate(DCR)and PFS between the non-CIP group and the CIP group.Out of the 86 CIP patients,50(58.14％)stopped immunotherapy,the other 36(41.86％)continued or restarted immunotherapy.One(1.16％)patient died of respiratory failure,and the remaining patients were relieved after drug withdrawal,hormone therapy,immunosuppressive therapy,etc.Conclusion The cancer patients with history of COPD or chest radiotherapy have a higher incidence of CIP after PD-1/PD-L1 treatment.Patients with advanced age are prone to high-grade CIP.Most CIP patients can achieve good outcomes after active treatment,and some with low-grade CIP can restart immunotherapy.

Enteroviruses are currently divided into groups A to J, among which groups A to D can infect human body. People infected with enterovirus can present invisible infection, which can lead to different clinical symptoms when the immunity is weakened. Among the diseases caused by enteroviruses, hand-foot-mouth disease, herpetic angina, and encephalitis have attracted much attention. Coxsackie virus A21 (CV-A21) belongs to enterovirus C group, which mainly causes acute respiratory tract infection. According to research reports, CV-A21 infection has been found in many countries and regions, and the infection scope is gradually expanding. In the past two years, it has been found that CV-A21 infection has a significant association with the outbreak of acute respiratory tract infection. This indicates that acute respiratory tract infection caused by CV-A21 infection may have potential public health problems. However, there are few studies on the epidemiology and pathogenic mechanism of this virus, and most of the studies are on the mechanism of its oncolytic action on specific malignant tumors. Therefore, in this paper, the structural characteristics, epidemiological characteristics, infection mechanism and oncolytic effects of CV-A21 are reviewed to provide relevant clues for the understanding and exploration of CV-A21.