OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

A patient with anti-MDA5-positive dermatomyositis complicated by hepatic dysfunction developed rhabdomyolysis after an intravenous injection of gadopentetate dimeglumine for magnetic resonance imaging.Analysis of clinical manifestations and medication correlation confirmed gadopentetate dimeglumineinduced rhabdomyolysis.Gadopentetate dimeglumine can cause rhabdomyolysis in dermatomyositis patients.Clinical conditions should be closely monitored when using gadopentetate dimeglumine to guard against adverse reactions.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Rheumatoid arthritis(RA)is a common autoimmune disease with synovitis as core pathological manifestation,with strong injury and high disability rate,which can not be cured completely at present.Recent studies have shown that tumor necro-sis factor receptor-related factor 6(TRAF6),as a ubiquitin ligase E3,plays a key role in autoimmune diseases and inflammatory diseases through a variety of pathways.This article reviews structure,function,ubiquitin regulation of TRAF6 and research progress of pathogenesis of RA.

A patient with anti-MDA5-positive dermatomyositis complicated by hepatic dysfunction developed rhabdomyolysis after an intravenous injection of gadopentetate dimeglumine for magnetic resonance imaging.Analysis of clinical manifestations and medication correlation confirmed gadopentetate dimeglumineinduced rhabdomyolysis.Gadopentetate dimeglumine can cause rhabdomyolysis in dermatomyositis patients.Clinical conditions should be closely monitored when using gadopentetate dimeglumine to guard against adverse reactions.

BACKGROUND:The therapeutic efficacy of moderate or severe intrauterine adhesions is poor.After synechotomy,the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age,which is an urgent problem to be solved in clinical practice.Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages,and they have received particular attention on the treatment of intrauterine adhesions.OBJECTIVE:To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.METHODS:Search terms were"mesenchymal stem cells,perinatal period,hydrogel,intrauterine adhesions,endometrial injury"in Chinese and English.Relative articles published from 2010 to 2024 were retrieved on PubMed,CNKI,and WanFang databases.As a result,80 articles that met the inclusion criteria were reviewed and analyzed.RESULTS AND CONCLUSION:(1)Similar to other sources of mesenchymal stem cells,perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions,and can meet the needs of autologous and allogeneic transplantation.(2)The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord,amniotic membrane,placenta,and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation,cellular immunity,paracrine,and promoting endometrial regeneration and angiogenesis,immune regulation,anti-endometrial cell apoptosis,inhibition of epithelial-mesenchymal transition,and anti-fibrosis.(3)Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions.On the basis of the effect of mesenchymal stem cells,the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells,promoting cell migration and adhesion,which is helpful to better promote endometrial regeneration and anti-fibrosis.It is beneficial to repair the damaged endometrial,improve endometrial receptivity and fertility,and reduce the recurrence rate.(4)A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions.Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels,and other effects and molecular mechanism of combined treatment of intrauterine adhesions.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.