ObjectiveTo evaluate the therapeutic effect and mechanism of tendon-management and patella-movement therapeutic manipulation in the treatment of patellofemoral arthritis based on imaging evaluation. MethodsTotally 126 patients with patellofemoral arthritis were recruited and divided into a treatment group and a control group according to a randomised numerical table. The control group received routine sodium hyaluronate injection once a week for a total of 5 times； the treatment group received tendon-management and patella-movement therapeutic manipulation three times a week for four weeks. We compared the Western Ontario and McMaster University osteoarthritis index score （WOMAC）， visual analogue scale （VAS）， imaging indicators including patellar external displacement distance， patellofemoral fit angle， lateral patellofemoral angle， and patellofemoral index， and overall effectiveness evaluation between the two groups before and one week after treatment. ResultsThe total effective rate of the treatment group （45/54， 83.33%） was significantly higher than that of the control group （36/54， 66.67%，P＜0.05）. One week after the end of treatment， the VAS scores and WOMAC scores of both groups were lower than those before treatment in the same group （P＜0.01）， and the patellofemoral index and patellofemoral fit angle of the treatment group decreased compared with that of the control group （P＜0.05）. Compared with the pre-treatment， the distance of patellar external displacement， patellofemoral index， and patellofemoral fit angle decreased in the treatment group 1 week after the end of treatment， and the patellofemoral fit angle decreased in the control group （P＜0.05）. ConclusionThe therapeutic manipulation of tendon-management and patella-movement can correct the degree of patellar external displacement， alleviate joint pain symptoms， improve joint function， and achieve the goal of treating patellofemoral arthritis.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective:To determine the content of the released nickel ion through the 7 extraction media to extract the Ni-Ti wires and to plot the curve of the released nickel ion so as to identify a leaching medium that can be substituted for blood for in vitro Ni release evaluation. Methods:The release of Ni through microwave digestion/inductively coupled plasma mass spectrometry (ICP-MS) in the goat serum was determined. Because of the high content of Ni release, it could be determined by diluting the extraction medium, and other extraction media could be determined directly. Ni release standard curves were plotted by the release amount and different time point variables. Though the different extraction media Ni release curves confirm the specificity of extraction media instead of blood.Results:By analyzing the Ni release curves of seven leaching media, it was found that none of these seven extraction media was suitable for the evaluation of Ni release in in vitro leaching media. Considering the safety of the leaching medium and the simplicity of preparation, hydrochloric acid solution was chosen as the leaching medium, but the concentration needed to be diluted accordingly. Finally, a hydrochloric acid solution was created as an alternative to blood for the in vitro study of Ni release from Ni-Ti alloy cardiovascular products, with a volume fraction of 0.005%. Conclusions:The in vitro leaching medium that can replace blood was found to be hydrochloric acid for the time being, but its concentration was too high, resulting in too much Ni release as well, which deviated from the actual situation. Therefore, the hydrochloric acid solution was diluted step by step, and the Ni release curve was examined until it was close to the clinical release level, and the actual concentration was determined, thus laying a solid foundation for the subsequent evaluation of the safety and risk.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

Aim To observe the behavioral effects of exogenous allopregnanolone(ALLO)and its inhibitor finasteride on the receptive period(R)and non-recep-tive period(NR)of PMDD liver-qi inversion model rats and the expression of GABAARα4,GABAARδ mR-NA and protein effects to explore its pathogenesis.Methods The PMDD liver-qi reverse syndrome rat model was prepared.The rats were divided into the normal group R and NR(control-R,control-NR),model group R and NR(Model-R,Model-NR),nor-mal group R+ALLO and NR+ALLO(Control+A-R,Control+A-NR),and model group R+ALLO and NR+ALLO(Model+A-R,Model+A-NR),model group R+finasteride and NR+finasteride(Model+F-R,Model+F-NR).The elevated cross labyrinth ex-periment and social interaction experiment were used to detect the behaviors of rats;fluorescence quantitative PCR and immunofluorescence were used to detect the expression of GABAARα4 and 8 mRNA and protein in rat amygdala and hippocampus.Results In the be-havioral evaluation,in the NR period,in the elevated cross maze test and in the social interaction test,the rats in the model group had anxiety behavior and de-creased social communication ability(P＜0.05),while the rats in the Model+A group could effectively relieve anxiety symptoms and improve their social com-munication ability(P＜0.05),and the rats in the Model+F group had increased anxiety behavior and social disorder(P＜0.05).In fluorescence quantita-tive PCR and immunofluorescence experiments,the ex-pression of GABAARα4 subunit in the model group was up-regulated in the hippocampus(P＜0.01),and the expression of δ subunit was down-regulated(P＜0.01);the expression of GABAARα4 subunit in the a-mygdala and hippocampus of the Model+A group de-creased(P＜0.01),and the expression of δ subunit increased in the hippocampus(P＜0.01).Conclu-sions The abnormal expression of GABAARα4 and 8 subunits mediated by ALLO improves the anxiety symptoms and social interaction ability of PMDD,which is the pathogenesis of PMDD liver-qi reverse syndrome,and provides basis and support for subse-quent exploration of the pathogenesis of PMDD liver-qi reverse syndrome.

Aim To observe the effects of Wenfei Jiangzhuo formula(WFJZF)on rats with vascular de-mentia and investigate its possible mechanism of ac-tion.Methods Thirty-six healthy male SD rats were randomly divided into the sham group,model group,donepezil group,and low-dose,medium-dose and high-dose groups of Wenfei Jiangzhuo formula,with six rats per group.Except for the sham group,the other groups were prepared as VaD models,and each group was gavaged with the corresponding drugs after suc-cessful modeling,and tests were performed after three weeks of treatment.Behavioral,hippocampal CA1 area morphology,neural dendrites and mitochondrial chan-ges were observed in all groups of rats,and phospho-glycerate mutase 5(PGAM5),dynamics-related pro-teins1(Drp1),opticatrophyprotein-1(OPA1),and other proteins were detected in each group.Results Compared with the sham group,rats in the model group and each intervention group had prolonged es-cape latency(P＜0.05),a shorter number of travers-als across the platforms(P＜0.05),a sparse morphol-ogy of hippocampal neurons,a reduction in the number of secondary dendritic spines,and a rupture of the out-er membrane of the mitochondria;the expression of the PGAM5 and Drp1 proteins in hippocampal tissues was elevated(P＜0.05),and the expression of the OPA1 and Mfn1/2 protein expression decreased(P＜0.05);compared with the model group,donepezil group and Wenfei Jiangzhuo formula high-dose group of rats had shorter evasion latency(P＜0.05),increased number of times to traverse the platform(P＜0.05),increased number of hippocampal neurons,tightly packed,more secondary dendritic structures,and reduced mitochon-drial damage;the expression of PGAM5 and Drp1 pro-teins was reduced(P＜0.05),and the expression of OPA1 and Mfn1/2 proteins was elevated(P＜0.05).Conclusions Wenfei Jiangzhuo formula can regulate the PGAM5-Drp1 signaling axis to improve the balance of mitochondrial homeostasis,thus improving the cog-nitive condition of the brain and exerting cerebroprotec-tive effects.

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:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.