OBJECTIVE:The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis.Currently,there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally.This article will comprehensively evaluate the methodological quality,reporting quality,and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.METHODS:Computer searches were conducted on CNKI,WanFang Data,VIP,CBM,PubMed,Embase,and The Cochrane Library.From the establishment of the database until January 24,2024,all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected.Two evaluators independently conducted literature screening and data extraction,and used the AMSTAR 2,PRISMA 2020,and GRADE systems to evaluate and summarize the methodological,reporting,and evidence quality of the included systematic reviews/meta-analyses.RESULTS:A total of 18 qualified systematic reviews/meta-analyses were included,and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid.The methodological quality of all 18 studies was extremely low;4 reports had poor quality and relatively serious information defects,while 14 reports had moderate quality and some information defects.Among the 275 outcome measures of 16 systematic reviews/meta-analyses,there were 9 medium quality evidence,90 low-quality evidence,and 176 extremely low-quality evidence,with no high-quality evidence.CONCLUSION:At present,the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low.In the future,the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration,research type explanation,retrieval strategy,exclusion list,research site and funding source,bias risk analysis,publication bias evaluation,and public information acquisition,and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

OBJECTIVE:The quality of systematic reviews/meta-analyses directly affects the reliability of clinical decision-making basis.Currently,there is no literature quality research on the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis both domestically and internationally.This article will comprehensively evaluate the methodological quality,reporting quality,and evidence quality of the systematic reviews/meta-analyses of platelet rich plasma versus hyaluronic acid in the treatment of knee osteoarthritis.METHODS:Computer searches were conducted on CNKI,WanFang Data,VIP,CBM,PubMed,Embase,and The Cochrane Library.From the establishment of the database until January 24,2024,all systematic reviews/meta-analyses treated with platelet rich plasma versus hyaluronic acid for knee osteoarthritis were collected.Two evaluators independently conducted literature screening and data extraction,and used the AMSTAR 2,PRISMA 2020,and GRADE systems to evaluate and summarize the methodological,reporting,and evidence quality of the included systematic reviews/meta-analyses.RESULTS:A total of 18 qualified systematic reviews/meta-analyses were included,and the results showed that the efficacy and safety of platelet rich plasma might be better than that of hyaluronic acid.The methodological quality of all 18 studies was extremely low;4 reports had poor quality and relatively serious information defects,while 14 reports had moderate quality and some information defects.Among the 275 outcome measures of 16 systematic reviews/meta-analyses,there were 9 medium quality evidence,90 low-quality evidence,and 176 extremely low-quality evidence,with no high-quality evidence.CONCLUSION:At present,the quality of systematic reviews/meta-analyses literature on the treatment of knee osteoarthritis with platelet rich plasma versus hyaluronic acid is relatively low.In the future,the authors of the systematic reviews need to strictly follow the entries of quality evaluation tools such as AMSTAR 2 and PRISMA 2020 in terms of plan registration,research type explanation,retrieval strategy,exclusion list,research site and funding source,bias risk analysis,publication bias evaluation,and public information acquisition,and conduct evidence quality evaluation on the combined results of the systematic reviews/meta-analyses to provide more reliable and rigorous evidence-based basis for clinical practice.

ObjectiveTo investigate the trends in diabetes mortality rate and the characteristics of decreased population in Fengxian District, Shanghai from 2012 to 2021. MethodsData from the death registration records of the residents in Fengxian District between 2012 and 2021, sourced from the Shanghai Death Surveillance System, were analyzed. Indicators such as the crude mortality rate due to diabetes, the standardized mortality rate, years of life lost (YLL), and the probability of premature death were estimated. Annual percentage change (APC) was used to analyze the temporal trends of mortality and the probability of premature death due to diabetes. Rate decomposition analysis was used to assess the contributions of demographic and non-demographic factors to diabetes mortality. ResultsFrom 2012 to 2021, there were 1 471 deaths due to diabetes in Fengxian District, with a crude mortality rate of 27.51/100 000 and a standardized mortality rate of 17.58/100 000. The crude mortality rate showed an overall increasing trend (APC=4.58%, Z=3.49, P<0.05). The potential years of life lost (PYLL) due to diabetes over this period amounted to 9 715 person-years, with a PYLL rate of 1.82 ‰, and the average years of life lost (AYLL) was 11.94 years. The probability of premature death was 0.41% (APC=3.36%, t=2.33, P<0.05). Both population aging and non-aging factors contributed to the increase in diabetes mortality, with overall contribution rates of 67.99% and 32.01%, respectively. Among men, the contribution rates were 60.57% and 39.43%, while among women, they were 79.43% and 20.57%, respectively. ConclusionFrom 2012 to 2021, both the crude mortality rate and the probability of premature death due to diabetes showed an upward trend among the residents in Fengxian District, with a higher YLL. Population aging was the main factor causing the increase in mortality rate, while non-demographic factors had a greater impact on the rise in diabetes mortality among men than that in women. Therefore, the management on male diabetes patients should be strengthened.

BACKGROUND:A pathophysiological feature of septic organ failure is endothelial dysfunction in sepsis(EDS).The physiological and pathological mechanism of sepsis is considered to be vascular leakage caused by endothelial dysfunction.These pathological changes lead to systemic organ injury.However,an analysis using bibliometric methods has not yet been conducted in the field of EDS.This study was conducted to provide an overview of knowledge structure and research trends in the field of EDS. METHODS:Based on previous research,a literature search was performed in the Web of Science Core Collection(WoSCC)for publications associated with EDS published between the year 2003 and 2023.Various types of data from the publications,such as citation frequency,authorship,keywords and highly cited articles,were extracted.The"Create Citation Report"feature in the WoSCC was employed to calculate the Hirsch index(h-index)and average citations per item(ACI)of authors,institutions,and countries.To conduct bibliometric and visualization analyses,three bibliometric tools were used,including R-bibliometrix,CiteSpace(co-citation analysis of references),and VOSviewer(co-authorship analysis of institutions,co-authorship analysis of authors,co-occurrence analysis of keywords). RESULTS:After excluding invalid records,the study finaly included 4,536 publications with 135,386 citations.Most of these publications originated in the USA,China,Germany,Canada,and Japan.Harvard University emerged as the most prolific institution,while professor Jong-Sup Bae and his research team at Kyungpook National University emerged as authors with the greatest influence.The"protein C","tissue factor","thrombin","glycocalyx","acute kidney injury","syndecan-1"and"biomarker"were identified as prominent areas of research.Future research may focus on molecular mechanisms(such as as vascular endothelial[VE]-cadherin regulation)and therapeutic interventions to enhance endothelial repair and function. CONCLUSION:Our findings show a growing interest in EDS research.Key areas for future research include signaling pathways,molecular mechanisms,endothelial repair,and interactions between endothelial cells and other cell types in sepsis.

AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P＜0.05 or P＜0.01),and the rate of EdU positive cells increased(P＜0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P＜0.05),and the myotube fusion index was raised(P＜0.05 or P＜0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P＜0.05 or P＜0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P＜0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P＜0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P＜0.05 or P＜0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Objective:This study aims to construct a human peripheral blood mononuclear cell(PBMC)-NPSG-PDX(patient-derived xenograft)model,by transferring PBMCs into NPSG(NOD-PrkdcscidIl2rgnull/Shjh)mice and transplanting human tumor tissues.This model mimics the human tumor microenvironment to investigate the interactions between tumors and the immune system.Methods:PBMCs from healthy donors were transferred to NPSG mice to generate hPBMC-NPSG model.Patient-derived xenografts(PDX)were established in nude(BALB/c-nu)mice.Third-generation PDX tumors were then transplanted into hPBMC-NPSG mice to establish the hPBMC-NPSG-PDX model.Mouse body weight was monitored,and flow cytometry was used to analyze immune reconstitution and T cell function.Tumor growth was evaluated,and immunohistochemistry was performed to analyze tumor morphology and immune cell infiltration.Results:Fourteen days after constructing the hPBMC-NPSG mouse model,the proportion of human hu-CD45+CD3+T cells reached 97％.The proportions of human CD8+T,CD4+T,CD56+natural killer(NK),and CD19+B cells were 64％,24％,4.6％,and 1.0％,respectively.Human CD4+and CD8+cells secreted various cytokines(IL-2,IFN-γ,and TNF-α)and expressed cytotoxic molecules(FasL,granzyme B,and perforin)28 days post reconstitution.Tumor growth in hPBMC-NPSG-PDX mice was rapid initially but then stabilized.Immunohistochemistry staining revealed typical tumor morphology,and tumor cell apoptosis was observed in areas with immune cell infiltration.Conclusion:This study successfully constructed a hPBMC-NPSG-PDX model that effectively simulates the human tumor microenvironment,providing an ideal platform for tumor immunology research.

Objective:This study aims to construct a human peripheral blood mononuclear cell(PBMC)-NPSG-PDX(patient-derived xenograft)model,by transferring PBMCs into NPSG(NOD-PrkdcscidIl2rgnull/Shjh)mice and transplanting human tumor tissues.This model mimics the human tumor microenvironment to investigate the interactions between tumors and the immune system.Methods:PBMCs from healthy donors were transferred to NPSG mice to generate hPBMC-NPSG model.Patient-derived xenografts(PDX)were established in nude(BALB/c-nu)mice.Third-generation PDX tumors were then transplanted into hPBMC-NPSG mice to establish the hPBMC-NPSG-PDX model.Mouse body weight was monitored,and flow cytometry was used to analyze immune reconstitution and T cell function.Tumor growth was evaluated,and immunohistochemistry was performed to analyze tumor morphology and immune cell infiltration.Results:Fourteen days after constructing the hPBMC-NPSG mouse model,the proportion of human hu-CD45+CD3+T cells reached 97％.The proportions of human CD8+T,CD4+T,CD56+natural killer(NK),and CD19+B cells were 64％,24％,4.6％,and 1.0％,respectively.Human CD4+and CD8+cells secreted various cytokines(IL-2,IFN-γ,and TNF-α)and expressed cytotoxic molecules(FasL,granzyme B,and perforin)28 days post reconstitution.Tumor growth in hPBMC-NPSG-PDX mice was rapid initially but then stabilized.Immunohistochemistry staining revealed typical tumor morphology,and tumor cell apoptosis was observed in areas with immune cell infiltration.Conclusion:This study successfully constructed a hPBMC-NPSG-PDX model that effectively simulates the human tumor microenvironment,providing an ideal platform for tumor immunology research.