Aim To explore the specific mechanism by which scutellarin(Scu)antagonizes the injury of human aortic endothelial cells(HAEC)induced by 2,2-azobis(2-methylpropylimidate)dihydrochloride(AAPH)by regulating the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-nuclear factor erythroid 2-related factor 2(NRF2)/ac-tivating transcription factor 4(ATF4)-C/EBP homology protein(CHOP)pathway.Methods HAEC were pre-pro-tected by Scu and then injured by AAPH to explore the molecular mechanism of Scu on HAEC injury.The cells were di-vided into control group,AAPH group,AAPH+Scu low,medium and high groups.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GSH-ST)in the cells were measured.The content of reactive oxygen species(ROS)in cells was detected by fluorescent probe,and the apop-tosis rate was detected by Annexin V-FITC/PI method.The mRNA expression of PERK and eIF2α in cells was detected by RT-qPCR.The protein expression of glucose regulated protein 78(GRP78),PERK,p-PERK,eukaryotic initiation factor 2α(eIF2α),p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,p53 up-regulated modulator of apoptosis(PUMA),Caspase-3 and Caspase-12 in cells was detected by Western blot.In order to further study the molecular mechanism of Scu against HAEC injury,gene silencing technology was used to inhibit the expression of PERK in HAEC.The cells were divided in-to five groups:control group,AAPH+si-con group,AAPH+Scu+si-con group,AAPH+si-PERK group,AAPH+si-PERK+Scu group.The mRNA expression of PERK and eIF2α in cells after si-PERK interference was detected by RT-qPCR.The protein expression of PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3 and Caspase-12 in cells after si-PERK interference was detected by Western blot.Results The content of ROS and the rate of apoptosis were significantly reduced after Scu intervention(P＜0.01).Scu could down-regulate the mRNA expression of PERK and eIF2α,and down-regulate the protein expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,Caspase-3,Caspase-12 and up-regulate the protein expression of Nrf2 and Bcl-2(P＜0.01).After interference with si-PERK,there were significant differences in the protein expression of PERK,p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3,Caspase-12,as well as the mRNA expression of PERK and eIF2α in cells compared to before interference(P＜0.01).It is proved that Scu could anti-endoplasmic role in reticulum stress and apoptosis,which is closely associated with the regula-tion of the PERK-Nrf2/ATF4-CHOP pathway.Conclusion Scu can effectively alleviate AAPH-induced injury to HAEC by regulating PERK-Nrf2/ATF4-CHOP pathways to inhibit endoplasmic reticulum stress and cell apoptosis.

Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.

Aim To explore the specific mechanism by which scutellarin(Scu)antagonizes the injury of human aortic endothelial cells(HAEC)induced by 2,2-azobis(2-methylpropylimidate)dihydrochloride(AAPH)by regulating the protein kinase RNA-like endoplasmic reticulum kinase(PERK)-nuclear factor erythroid 2-related factor 2(NRF2)/ac-tivating transcription factor 4(ATF4)-C/EBP homology protein(CHOP)pathway.Methods HAEC were pre-pro-tected by Scu and then injured by AAPH to explore the molecular mechanism of Scu on HAEC injury.The cells were di-vided into control group,AAPH group,AAPH+Scu low,medium and high groups.The contents of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px)and glutathione S-transferase(GSH-ST)in the cells were measured.The content of reactive oxygen species(ROS)in cells was detected by fluorescent probe,and the apop-tosis rate was detected by Annexin V-FITC/PI method.The mRNA expression of PERK and eIF2α in cells was detected by RT-qPCR.The protein expression of glucose regulated protein 78(GRP78),PERK,p-PERK,eukaryotic initiation factor 2α(eIF2α),p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,p53 up-regulated modulator of apoptosis(PUMA),Caspase-3 and Caspase-12 in cells was detected by Western blot.In order to further study the molecular mechanism of Scu against HAEC injury,gene silencing technology was used to inhibit the expression of PERK in HAEC.The cells were divided in-to five groups:control group,AAPH+si-con group,AAPH+Scu+si-con group,AAPH+si-PERK group,AAPH+si-PERK+Scu group.The mRNA expression of PERK and eIF2α in cells after si-PERK interference was detected by RT-qPCR.The protein expression of PERK,p-eIF2α,eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3 and Caspase-12 in cells after si-PERK interference was detected by Western blot.Results The content of ROS and the rate of apoptosis were significantly reduced after Scu intervention(P＜0.01).Scu could down-regulate the mRNA expression of PERK and eIF2α,and down-regulate the protein expression of GRP78,p-PERK,p-eIF2α,ATF4,CHOP,PUMA,Caspase-3,Caspase-12 and up-regulate the protein expression of Nrf2 and Bcl-2(P＜0.01).After interference with si-PERK,there were significant differences in the protein expression of PERK,p-eIF2α,ATF4,CHOP,Nrf2,Bcl-2,PUMA,Caspase-3,Caspase-12,as well as the mRNA expression of PERK and eIF2α in cells compared to before interference(P＜0.01).It is proved that Scu could anti-endoplasmic role in reticulum stress and apoptosis,which is closely associated with the regula-tion of the PERK-Nrf2/ATF4-CHOP pathway.Conclusion Scu can effectively alleviate AAPH-induced injury to HAEC by regulating PERK-Nrf2/ATF4-CHOP pathways to inhibit endoplasmic reticulum stress and cell apoptosis.

Objective:To characterize the epidemiology, antimicrobial susceptibility, and molecular mechanisms of carbapenem-resistant Enterobacterales (CRE) carrying multiple carbapenemase genes in China, and to provide evidence for infection control and antibiotic stewardship.Methods:From 2016 to 2023, 115 CRE isolates harboring at least two carbapenemase genes were collected from 41 hospitals in 18 provinces across China. Species identification, antimicrobial susceptibility testing, and whole-genome sequencing were performed. Multilocus sequence typing (MLST) and capsular typing were conducted using Kleborate, plasmid replicon types were identified with PlasmidFinder, and a core genome phylogenetic tree was constructed.Results:The majority of isolates belonged to Klebsiella spp. (80.0%, 92/115), followed by E. cloacae (8.7%, 10/115) and E. coli (6.1%, 7/115). The isolates were mainly from Hebei, Beijing, Shandong, and Hunan (60.9%, 70/115), and sputum was the predominant specimen (43.5%, 50/115). The most common genotype was bla KPC+bla NDM (73.0%, 84/115), primarily in Klebsiella spp. (79.8%, 67/84), followed by bla NDM+bla IMP (15.7%, 18/115). The prevalent plasmid replicon types were IncFII (77.5%, 86/111), IncFIB (68.5%, 76/111), IncR (51.4%, 57/111), and IncX3 (20.7%, 23/111). Notably, 88.6% (31/35) of ST11-KL64 K. pneumoniae strains co-harbored IncFII, IncFIB, and IncR plasmids simultaneously. Between 2016 and 2022, the dominant subtype among Klebsiella spp. isolates was bla KPC-2+bla NDM-1 (56.2%, 36/64). In 2023, the bla KPC-2+bla NDM-13 subtype (29.5%, 19/64) emerged and exhibited clonal transmission (single nucleotide polymorphism 2?74 bp) in Hebei, Beijing, and Jilin. Susceptibility testing showed widespread resistance to β-lactams (90.2%-100%). Aztreonam-avibactam, tigecycline, and colistin retained high activity, with susceptibility rates of 90.16%-98.36%. Conclusions:In China, the majority of clinical Enterobacteriaceae strains that harbor multiple carbapenemases are Klebsiella spp. co-producing KPC and NDM enzymes. Dissemination is driven by both clonal expansion of ST11-KL64 and horizontal transfer of IncFII, IncFIB, and IncR plasmids. The recent emergence and regional clonal spread of the bla KPC-2+bla NDM-13 genotype underscore the urgent need for strengthened surveillance and containment measures.

To evaluate the effects of non-pharmacological interventions on cognitive function and activities of daily living in patients with post-stroke cognitive impairment (PSCI).Methods:Based on Cochrane Library, PubMed, Web of Science, Embase, CNKI, WanFang, and VIP databases, randomized controlled studies on rehabilitation therapy for PSCI patients were retrieved. And the retrieval date was from the establishment of the databases to 31 December 2021. Literature screening, data extraction, quality evaluation and data analysis were carried out.Results:A total of 26 studies were included, involving 12 interventions and 2007 patients with PSCI. The results of network Meta-analysis showed that compared with routine rehabilitation and/or routine rehabilitation care, cognitive therapy ( SMD=-1.30, 95% CI -2.09 - -0.52)、repetitive transcranial magnetic stimulation ( SMD=-1.67, 95% CI -2.54 - -0.81; SMD=-2.34, 95% CI -3.71 - -0.97), repetitive transcranial magnetic stimulation combined with cognitive therapy ( SMD=-1.56, 95% CI -2.76 - -0.36; SMD=-2.23, 95% CI -3.39 - -1.07), acupuncture combined with cognitive therapy ( SMD=-2.31, 95% CI -3.51 - -1.12; SMD=-2.98, 95% CI -4.13 - -1.84), virtual reality ( SMD=-1.01, 95% CI -1.98 - -0.04; SMD=-1.68, 95% CI -2.98 - -0.38), computer-assisted cognitive training combined with cognitive therapy ( SMD=-2.50, 95% CI -4.35 - -0.65; SMD=-3.17, 95% CI -4.99 - -1.35), music therapy ( SMD=-1.47, 95% CI -2.61 - -0.33), music therapy combined with cognitive therapy ( SMD=-2.35, 95% CI -4.04 - -0.67), recreational therapy ( SMD=-2.11, 95% CI -3.93 - -0.30), guided imagination therapy ( SMD=-2.48, 95% CI -4.00 - -0.96) had statistical significance in improving the cognitive function of PSCI patients ( P<0.05); recreational therapy ( SMD=-3.57, 95% CI -6.09 - -1.04; SMD=-3.70, 95% CI -7.22 - -0.18) had statistical significance in improving the ability of daily living activities of PSCI patients ( P<0.05). According to the area ranking results under the cumulative ranking probability graph, acupuncture combined with cognitive therapy (89.2%) and recreational therapy (85.1%) ranked first in improving cognitive function and activities of daily living, respectively. Conclusions:Acupuncture combined with cognitive therapy and recreational therapy have the best effect on improving cognitive function and activities of daily living in PSCI patients, respectively. However, considering the poor quality of the original literature included, more large samples and high-quality RCTs are needed for further verification.

Objective:To analyze the current status, hotspots and frontiers of pain catastrophizing at home and abroad from 2012 to 2022, so as to provide reference for research on pain catastrophizing in China.Methods:Article retrieval were conducted on the Web of Science, China National Knowledge Infrastructure, WanFang Data and VIP using the Chinese and English keywords "pain catastrophizing". The search period was from January 1, 2012 to August 24, 2022. The articles were analyzed using the CiteSpace software.Results:A total of 2036 English articles and 83 Chinese articles were included. The overall number of articles was increasing year by year, with the countries and institutions with the highest publication volume being the United States and the University of Washington. Research hotspots at home and abroad included pain, low back pain, quality of life, influencing factors, anxiety, depression, joint replacement, scale validation, kinesiophobia and so on.Conclusions:The research on pain catastrophizing abroad is increasingly receiving widespread attention, while domestic research is still in its infancy. Domestic researchers can use various methods to explore the occurrence and influencing factors of pain catastrophizing among different disease groups in China, deeply explore the mechanism of pain catastrophizing, and focus on the correlation between pain catastrophizing and exercise rehabilitation outcomes to help patients cope with pain.

Retinal pigment epithelium(RPE)has essential functions,such as nourishing and sup-porting the neural retina,and is of vital importance in the pathogenesis of age-related retinal degen-eration.However,the exact molecular changes of RPE during aging remain poorly understood.Here,we isolated human primary RPE(hRPE)cells from 18 eye donors distributed over a wide age range(10-67 years old).A quantitative proteomic analysis was performed to analyze changes in their intracellular and secreted proteins.Age-group related subtypes and age-associated proteins were revealed and potential age-associated mechanisms were validated in ARPE-19 and hRPE cells.The results of proteomic data analysis and verifications suggest that RNF123-and RNF149-related protein ubiquitination plays an important role in protecting hRPE cells from oxidative damage dur-ing aging.In older hRPE cells,apoptotic signaling-related pathways were up-regulated,and endo-plasmic reticulum organization was down-regulated both in the intracellular and secreted proteomes.Our work paints a detailed molecular picture of hRPE cells during the aging process and provides new insights into the molecular characteristics of RPE during aging and under other related clinical retinal conditions.

Objective:To investigate the willingness of medical students to work in primary health care institutions.Methods:A cross-section survey was conducted to investigate the willingness and the reasons, involving 597 undergraduate medical students and 2088 junior college students.Results:The employment willingness of undergraduate medical students was relatively low (14.9%), while the employment willingness of junior college students was high (56.02%). The top three factors of low employment willingness were: less opportunities for personal development, poor working environments and welfare. Moreover, the most effective method to cultivate medical students was developing a free training project for rural-oriented medical students, and the best method to attract medical students was formulating a more beneficial comprehensive policy.Conclusion:The willingness of clinical medical students to be employed in primary health care institutions is low for the time being. It is suggested to improve their willingness by improving welfare benefits, providing personal development opportunities, and strengthening social security.

Objective To systematically evaluate the effect of case management model in patients with breast cancer in China. Methods The internet-based retrieval was done through SinoMed, CNKI, WANFANG data, VIP, Pubmed and Web of Science (WOS) with case management model of breast cancer patients in the randomized controlled trails. Data extraction and quality evaluation were conducted from the acquired literature. Results Eight studies were included. The case management was showed to improve the treatment compliance of patients with breast cancer and the satisfaction of patients effectively. It also reduced hospitalization time and hospitalization costs of the patients, improve the quality of life and social psychological adaptability. Conclusion The application of case management model is effective, but the case management model is still in the initial stage in China, needing to be strengthened.

OBJECTIVE:To investigate the effects of plasma exchange (PE) combined with intensive insulin glycemic control on related indexes of patients with HLP.METHODS:A total of 120 HLP patients were randomly divided into control group (60 cases) and observation group (60 cases).Based on routine treatment,2 groups were given PE treatment for 3 times+Low molecular weight heparin calcium for injection 5 000 U subcutaneously+Methylprednisolone sodium succinate for injection 40 mg intravenously+Calcium gluconate injection 2 g intravenously.Based on it,Insulin injection was pumped to random blood glucose ＜12 mmol/L with a micro-infusion pump in control group when random blood glucose concentration was equal to or more than 12 mmol/ L.When random blood glucose of patients in observation group were higher than 8.3 mmol/L,Insulin injection was pumped with a micro-infusion pump for a week and random blood glucose concentration was maintained at 6.1-8.3 mmol/L.Plasma levels of triglyceride,PCT,WBC count,APACHE Ⅱ score,Balthazar CT score,length of hospitalization stay in ICU and the occurrence of ADR were observed in 2 groups before and after treatment.RESULTS:After treatment,plasma levels of triglyceride,amylase and PCT,WBC count,APACHE Ⅱ score and Balthazar CT score in 2 groups were significantly lower than before treatment,and the observation group was significantly lower than the control group,with statistical significance(P＜0.05).Length of hospitalization stay in ICU observation group was significantly shorter than control group,with statistical significance(P＜0.05).There was no statistical significance in the incidence of ADR between 2 groups(P＞0.05).CONCLUSIONS:PE combined with intensive insulin glycemic control can effectively reduce the level of plasma triglyceride,relieve inflammatory reaction and improve prognosis without increasing the occurrence of ADR.