Objective To prepare Zanthoxylum alkaloid thermosensitive hydrogel, optimize the preparation process and conduct related performance studies. Methods Zanthoxylum alkaloids were obtained by reflux extraction, followed by enrichment and purification using macroporous adsorption resin. Poloxamer 407 and Poloxamer 188 were used as substrates to prepare the thermosensitive hydrogel of Zanthoxylum alkaloids, and the preparation process was optimized by orthogonal design. The quality of the hydrogel was systematically evaluated based on its gelation temperature, gelation time, Fourier transform infrared （FTIR） spectroscopy, scanning electron microscopy （SEM） images, mechanical properties, and in vitro release profile. Results The optimal preparation conditions for the Zanthoxylum alkaloid thermosensitive hydrogel were: 20% （g/ml） poloxamer 407, 2% （g/ml） poloxamer 188 and 100 μg/ml Zanthoxylum alkaloid. The gelation temperature was 32.6℃, and the average gelling time was 143.3 s. The hydrogel appeared as a transparent liquid at room temperature and was transformed into a semi-solid gel state when the temperature exceeded 33℃. Experimental results confirmed the successful preparation of poloxamer 407 and poloxamer 188 thermosensitive hydrogel loaded with Zanthoxylum alkaloids, which exhibited good bio adhesion, self-healing properties, and tensile strength. Conclusion The Zanthoxylum alkaloid thermosensitive hydrogel demonstrated favorable mechanical properties and a sustained-release effect, showing promising potential for further development and application.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P＜0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P＜0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P＜0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

OBJECTIVE To investigate the role and mechanism of paeonol in inhibiting the migration of bladder cancer T24 cells by regulating nuclear factor κB(NF-κB)/hypoxia-inducible factor-1α(HIF-1α)-mediated aerobic glycolysis.METHODS T24 cells were divided into control group,cisplatin group(positive control,3.001 μg/mL),and paeonol low-,medium-and high-dose groups(100,200,400 μg/mL),respectively.After 24 h of administration intervention,the effect of paeonol on the migration ability of T24 cells was detected(expressed by the cell scratch wound healing rate).The effect of paeonol on the mitochondrial membrane potential of T24 cells was detected(expressed by the ratio of red/green fluorescence intensity).Cellular adenosine triphosphate(ATP)levels and lactate content in T24 cells were measured.The levels of NF-κB/HIF-1α signaling pathway,the expression of migration-related proteins,and key enzymes involved in aerobic glycolysis in the cells were all determined.RESULTS Compared with the control group,the cell scratch wound healing rates in the paeonol medium-and high-dose groups and the cisplatin group were decreased significantly(P＜0.01);in the paeonol groups,the expression levels of NF-κB/HIF-1α signaling pathway-related proteins such as NF-κB and HIF-1α,migration-related proteins such as matrix metalloproteinase 2(MMP2),MMP9,and vascular endothelial growth factor,as well as key enzymes involved in aerobic glycolysis such as glucose transporter 1,hexokinase 2 and pyruvate kinase isozyme type M2,were all reduced to varying degrees in the cells,most of these reductions showed statistically significant differences(P＜0.05 or P＜0.01);the ratio of red/green fluorescence intensity in mitochondria of cells in the medium-and high-dose paeonol groups were significantly decreased(P＜0.01);the ATP concentration in cells of the paeonol high-dose group,and the lactate content in cells across all paeonol groups were significantly decreased(P＜0.05 or P＜0.01).CONCLUSIONS Paeonol significantly inhibits the migration of bladder cancer T24 cells,and its mechanism of action may be related to the inhibition of the NF-κB/HIF-1α signaling pathway,and the down-regulation of key enzyme activities involved in aerobic glycolysis.

Objective To investigate the therapeutic effect and underlying mechanism of action of a CXCR3 inhibitor in rheumatoid arthritis(RA)in mice model.Methods Thirty BALB/C mice were randomly divided into control,model,and treatment groups.RA model was established in both the model and treatment groups using a collagen induction method.Upon successful modeling,mice in the treat-ment group received a daily oral administration of 1 mg/kg SCH 546738(CXCR3 inhibitor)for 4 weeks,whereas those in the control and model groups received equivalent volumes of saline.During treatment,the weekly arthritis index scores of mice were recorded.The expres-sion of TNF-α,IFN-γ,and IL-1β in joint tissues was determined based on Western blotting and qRT-PCR analyses.In addition,we used flow cytometry to assess peripheral blood Th1/Th2 cell ratios,and serum levels of IFN-γ and IL-4 were measured using ELISA.Peripheral blood CD4+T cells were isolated and co-incubated with SCH 546738,and subsequently assessed as CD4+T and CD4+T+SCH 546738 groups.In addition,Th1/Th2 cell ratios were assessed using flow cytometry.Results Compared with the control group,mice in the model group were characterized by elevated weekly arthritic index scores,increases in the joint tissues expression of TNF-α,IFN-γ,and IL-1β,heightened peripheral blood Th1/Th2 cell ratios,and raised serum IFN-γ levels(P＜0.05).In contrast to the model group,the treatment group mice had lower weekly arthritis index scores,reductions in the joint tissue expression of TNF-α,IFN-γ,and IL-1β,diminished peripheral blood Th1/Th2 cell ratios,and lowered serum IFN-γ levels(P＜0.05).Moreover,compared with the CD4+T group,the CD4+T+SCH 546738 group was characterized reduced Th1/Th2 cell ratios(P＜0.001).Conclusion The CXCR3 inhibitor SCH 546738 can alle-viate the progression of RA in mice by reducing Th1/Th2 cell ratios,thereby ameliorating the immune response.

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Objective To assess the sweat secretion of Yin-deficient ovariectomized rats and investigate the changes in biochemical indexes.Methods Eighteen SD female rats were randomly divided into a sham operation group,model group,and positive control group of six rats each.The rats in the sham operation group underwent a sham operation,and those in the model group and positive control group underwent bilateral ovariectomy.L-Thyroxine(92 mg/kg)was given once a day for 7 consecutive days starting on the 7th postoperative day to establish a Yin-deficient ovariectomized model.The rats in the positive control group were orally administered Qinggu San Tang(7.3 g/kg)once a day,while those in the sham operation group and model group were orally administered an equal amount of distilled water once a day for a total of 14 days.Sweat secretion from the plantar region of the foot was measured using the Wada-Takagaki reagent coloring method.At the end of the experiment,blood was taken from the abdominal aorta and the tissue of the paw pads was separated.The serum levels cyclic adenosine monophosphate(cAMP),cyclic guanosine monophosphate(cGMP),luteinizing hormone(LH),gonadotropin-releasing hormone(GnRH),and estradiol(E2)were measured by enzyme-linked immunosorbent assay.Western Blot was used to determine the expression levels of M3 R,β2 AR,and aquaporin-5(AQP5)in the paw pad.Results The three main findings of this study were as follows.(1)Compared with the rats in the sham operation group,those in the model group were more irritable and aggressive,and their body weights decreased while their average temperature and sweat secretion significantly increased.(2)Serum cAMP level and cAMP/cGMP ratio increased,the LH and GnRH levels significantly increased,and the E2 level decreased.(3)M3 R expression was down-regulated and β2 AR and AQP5 expression was up-regulated in the paw pads of the rats.After 2 weeks of positive control treatment,the serum cAMP level and cAMP/cGMP ratio significantly decreased and the LH and GnRH levels decreased;however,no statistically significant difference was observed in the serum E2 level.The expression levels of M3 R were increased-regulated in paw pads of the rats,and reduced expression of β2 AR and AQP5.Conclusions Sweat secretion significantly increased in this"combined disease and evidence"model of perimenopausal syndrome kidney yin deficiency established by desiccation combined with thyroxine.The underlying mechanism may be related to the changes in cGMP,cAMP,and key proteins M3 R,β2 AR,and AQP5 in sweat glands that regulate sweat secretion.

Objective To understand the change trend of doctor trustrank among the residents,and to analyze its influencing factors to provide reference for finding the effective strategies to enhance the doctor trustrank.Methods The analytical framework was constructed based on the social determinism.The data from the China Family Panel Studies(CFPS)in 2014,2016,2018 and 2020 were adopted to analyze the change trend of residents'doctor trustrank.The OLS regression model was used to explore the influencing factors,and the Shapley value decomposition model was used to analyze the contribution degree of influencing factors on doctor trustrank.Results The residents'doctor trustrank was gradually decreased in 2014,2016 and 2018(6.817,6.762,6.730),which in 2020 was significantly increased(7.151).The OLS regression model analysis showed that the personal characteristics,social trust,quality of medical services,access to information and subjective socioeconomic status were related to the residents'doctor trustrank.The social trust during 2014-2020 was the main factor affecting the residents'doctor trustrank,followed by the medical service quality,subjective socialeconomic status and information channels.The personal characteristics had the lowest contri-bution degree to doctor trustrank.Conclusion The residents'doctor trustrank is comprehensively affected by the factors such as social trust,medical service quality,subjective socioeconomic status and information chan-nels.It is needed to optimize the comprehensive treatment measures to promote the persistent elevation of doctor trustrank.