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 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 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 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.

Background:The overall Helicobacter pylori(Hp)infection rate in China is relatively high,with significant regional variations.Currently,there is a lack of large-sample surveys on the Hp infection rate in the general population of Xinjiang.Aims:To explore the Hp infection rate in the Xinjiang Uygur Autonomous Region and provide a reference for the prevention and control strategies of Hp infection in this region.Methods:A stratified random cluster sampling method was used to select 4 361 individuals from the general population in 15 regions of the Xinjiang Uygur Autonomous Region.Hp antibody testing was performed to assess Hp infection status.Results:The overall Hp infection rate in Xinjiang was 71.57％(3 121/4 361).The Hp infection rate showed a trend of first increasing and then decreasing with age,but the difference was not statistically significant(x2=11.992,P＞0.05).There was a statistically significant difference in the Hp infection rate among different residential areas(x2=250.316,P＜0.01).The Hp infection rates among ethnic minorities such as Uyghurs and Tajiks were significantly higher than those among Han and Hui ethnic groups,and the difference was statistically significant(x2=200.797,P＜0.01).The Hp infection rate gradually increased with the increase in altitude,and the difference was statistically significant(x2=33.366,P＜0.01).Conclusions:This study revealed that the overall Hp infection rate in Xinjiang is relatively high,with obvious differences in residential areas,ethnic groups,and altitudes.More powerful publicity and education,screening methods,and eradication strategies should be implemented for ethnic minorities in different regions.

Objective:To analyze the clinical characteristics of ulcerative colitis (UC) in Han and Uyghur patients in Xinjiang Uygur Autonomous Region.Method:Data of UC patients hospitalized at the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2015 to June 2023 were retrospectively collected, with a focus on the differences in basic information, extraintestinal manifestations and biochemical laboratory indicators between Han and Uyghur patients.Results:A total of 315 UC patients were included, with 172 Han cases (54.6%) and 143 Uyghur cases (45.4%) . Compared to the Han group, the Uyghur group had a higher proportion of females, a lower average age, and lower rates of smoking and alcohol consumption (all P<0.05) . The Uyghur group showed a higher prevalence of hepatobiliary diseases and joint injuries as extraintestinal manifestations, although the differences were not statistically significant ( P all>0.05) . The Han group had a statistically significant higher level of intraepithelial neoplasia (χ 2 = 5.075, P<0.05) . The Uyghur group exhibited significantly higher levels of white blood cell count, platelet count, neutrophils, lymphocyte count, globulin, C-reactive protein, erythrocyte sedimentation rate, highly sensitive C-reactive protein, anti-neutrophil cytoplasmic antibodies, and H.pylori antibodies compared to the Han group (all P<0.05) . Both Han and Uyghur UC patients achieved satisfactory clinical efficacy. Conclusion:Uyghur UC patients have distinct characteristics, including a younger age of onset and more severe disease course, yet appropriate treatment can lead to satisfactory clinical outcomes.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.