ObjectiveThis study aims to investigate the dynamic changes in general body parameters, blood glucose, and blood lipid profiles in obese cynomolgus monkeys, exploring the correlations among these parameters and providing a reference for research on the obese cynomolgus monkey model. Methods30 normal male cynomolgus monkeys aged 5 - 17 years old (with body mass index < 35 kg/m² and glycated hemoglobin content < 4.50%) and 99 spontaneously obese male cynomolgus monkeys (with body mass index ≥35 kg/m² and glycated hemoglobin content < 4.50%) were selected. Over a period of three years, their abdominal circumference, skinfold thickness, body weight, body mass index, fasting blood glucose, glycated hemoglobin, and four blood lipid indicators were monitored. The correlations between each indicator were analyzed using repeated measurement ANOVA, simple linear regression, and multiple linear regression correlation analysis method. Results Compared to the control group, the obese group exhibited significantly higher levels of abdominal circumference, skinfold thickness, body weight, body mass index, and triglyceride (P＜0.05). In the control group, skinfold thickness increased annually, while other indicators remained stable. Compared with the first year, the obese group showed significantly increased abdominal circumference, skinfold thickness, body weight, body mass index, triglyceride, and fasting blood glucose in the second year(P＜0.05), with this increasing trend persisting in the third year (P＜0.05). In the control group, the obesity incidence rates in the second and third years were 16.67% and 23.33%, respectively, while the prevalence of diabetes remained at 16.67%. In the obese group, the diabetes incidence rates were 29.29% and 44.44% in years 2 and 3, respectively. Among the 11-13 year age group, the incidence rates were 36.36% and 44.68%, while for the group older than 13 years, the rates were 28.13% and 51.35%. Correlation analysis revealed significant associations (P＜0.05) between fasting blood glucose and age, abdominal circumference, skinfold thickness, body weight, and triglyceride in the diabetic monkeys. Conclusion Long-term obesity can lead to the increases in general physical indicators and fasting blood glucose levels in cynomolgus monkeys, and an increase in the incidence of diabetes. In diabetic cynomolgus monkeys caused by obesity, there is a high correlation between their fasting blood glucose and age, weight, abdominal circumference, skinfold thickness, and triglyceride levels, which is of some significance for predicting the occurrence of spontaneous diabetes.

Objective:To explore the effect of combining repeated peripheral (rPMS) and central transcranial magnetic stimulation (rTMS) in treating upper limb motor dysfunction after a stroke.Methods:Seventy-eight patients with upper limb motor dysfunction after a stroke were randomly divided into a control group, an rTMS group and a combined magnetic stimulation group, each of 26. All three groups underwent routine rehabilitation, while the rTMS group was repeatedly given low frequency transcranial magnetic stimulation of the M1 region on the unaffected side, and the combined group also received repeated peripheral magnetic stimulation at Erb′s point on the affected upper limb. There was one treatment session a day, 5 days a week for 3 weeks. Before and after the treatment, everyone′s upper limb motor function was quantified using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT). Skill in the activities of daily living was quantified in terms of a Barthel index (BI). Motor recovery of the upper limbs and hands was assessed using Brunnstrom staging. The latency and amplitude of the motor evoked potentials (MEPs) in the subjects′ affected abductor pollicis brevis muscles were also recorded before and after the treatment. Pearson correlation coefficients quantified the correlation between the changes in FMA-UE scores and MEP amplitudes before and after the treatment in the three groups.Results:There were no significant differences among the three groups before the treatment. Afterward, however, the average FMA-UE, WMFT and BI scores, as well as the upper limb and hand Brunnstrom stages and the average MEP latencies and amplitudes of all the three groups had improved significantly. The combined group′s average results were then significantly better than the other two groups′ averages, except for the upper limb Brunnstrom stages. The increases in MEP amplitude were positively correlated with the increases in FMA-UE scores among the rTMS and the combined group, but there was no significant correlation between them in the control group.Conclusions:The combined application of rPMS and contralateral low frequency rTMS can effectively relieve motor dysfunction in the upper limbs in the early stages after a stroke.

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 explore the regulatory role of N-methyl berbamine(N-MB)in intracellular calcium homeostasis in H9c2 car-diomyocytes,and,thereby,clarify the possible mechanism of the myocardial protective effect of N-MB.Methods Binding of N-MB to CaV1.2 channels was simulated using the MOE software,and the binding affinity and binding mode were determined.The hCaV1.2 gene was transfected into HEK293 cells,and the effect of N-MB(30 μmol/L)on the CaV1.2 current was detected using the whole-cell patch clamp technique.In addition,a Fluo 3-AM fluorescent probe was loaded into H9c2 cardiomyocytes,and the effect of N-MB(3,30 μmol/L)on intracellular calcium ion concentration was observed under a laser confocal microscope.The effect of N-MB(3,30 μmol/L)on the expression of Ca2+regulation-related genes Cacna1c,Cacnb2,Ryr2,Serca2a,and Ncx1 in H9c2 cardiomyocytes was examined using real-time quantitative PCR.Results N-MB was predicted to bind to CaV1.2 channels.The binding sites mainly involved Phe1191,Thr1420,and Asn771,and the binding modes were H-donor,pi-pi,and pi-H.N-MB(30 μmol/L)significantly inhibited CaV1.2 currents,with an inhibition rate of 76.09％±7.41％.The fluorescence intensity of intracellular Ca2+level in H9c2 cardiomyocytes was significantly enhanced with N-MB treatment(3,30 μmol/L,P＜0.01).Compared with the control group,differences in the expression of Cacna1c,Serca2a,and Ncx1 in H9c2 cardiomyocytes were not significant after N-MB(3,30 μmol/L)intervention(P＞0.05),whereas the expression of Cacnb2 significantly reduced(P＜0.001)and the expression of Ryr2 significantly increased(P＜0.05).Conclusion N-MB binds to CaV1.2 calcium channels.N-MB may regulate intracellular calcium homeostasis by inhibiting calcium currents by decreasing the gene expression of CaV1.2 calcium channels.Additionally,N-MB may also increase intracellular Ca2+concentration by promoting the expression of Ryr2,which could be the mechanism underlying the myocardial protective effect of N-MB.

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 explore the regulatory role of N-methyl berbamine(N-MB)in intracellular calcium homeostasis in H9c2 car-diomyocytes,and,thereby,clarify the possible mechanism of the myocardial protective effect of N-MB.Methods Binding of N-MB to CaV1.2 channels was simulated using the MOE software,and the binding affinity and binding mode were determined.The hCaV1.2 gene was transfected into HEK293 cells,and the effect of N-MB(30 μmol/L)on the CaV1.2 current was detected using the whole-cell patch clamp technique.In addition,a Fluo 3-AM fluorescent probe was loaded into H9c2 cardiomyocytes,and the effect of N-MB(3,30 μmol/L)on intracellular calcium ion concentration was observed under a laser confocal microscope.The effect of N-MB(3,30 μmol/L)on the expression of Ca2+regulation-related genes Cacna1c,Cacnb2,Ryr2,Serca2a,and Ncx1 in H9c2 cardiomyocytes was examined using real-time quantitative PCR.Results N-MB was predicted to bind to CaV1.2 channels.The binding sites mainly involved Phe1191,Thr1420,and Asn771,and the binding modes were H-donor,pi-pi,and pi-H.N-MB(30 μmol/L)significantly inhibited CaV1.2 currents,with an inhibition rate of 76.09％±7.41％.The fluorescence intensity of intracellular Ca2+level in H9c2 cardiomyocytes was significantly enhanced with N-MB treatment(3,30 μmol/L,P＜0.01).Compared with the control group,differences in the expression of Cacna1c,Serca2a,and Ncx1 in H9c2 cardiomyocytes were not significant after N-MB(3,30 μmol/L)intervention(P＞0.05),whereas the expression of Cacnb2 significantly reduced(P＜0.001)and the expression of Ryr2 significantly increased(P＜0.05).Conclusion N-MB binds to CaV1.2 calcium channels.N-MB may regulate intracellular calcium homeostasis by inhibiting calcium currents by decreasing the gene expression of CaV1.2 calcium channels.Additionally,N-MB may also increase intracellular Ca2+concentration by promoting the expression of Ryr2,which could be the mechanism underlying the myocardial protective effect of N-MB.

Objective:To explore the effect of combining repeated peripheral (rPMS) and central transcranial magnetic stimulation (rTMS) in treating upper limb motor dysfunction after a stroke.Methods:Seventy-eight patients with upper limb motor dysfunction after a stroke were randomly divided into a control group, an rTMS group and a combined magnetic stimulation group, each of 26. All three groups underwent routine rehabilitation, while the rTMS group was repeatedly given low frequency transcranial magnetic stimulation of the M1 region on the unaffected side, and the combined group also received repeated peripheral magnetic stimulation at Erb′s point on the affected upper limb. There was one treatment session a day, 5 days a week for 3 weeks. Before and after the treatment, everyone′s upper limb motor function was quantified using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT). Skill in the activities of daily living was quantified in terms of a Barthel index (BI). Motor recovery of the upper limbs and hands was assessed using Brunnstrom staging. The latency and amplitude of the motor evoked potentials (MEPs) in the subjects′ affected abductor pollicis brevis muscles were also recorded before and after the treatment. Pearson correlation coefficients quantified the correlation between the changes in FMA-UE scores and MEP amplitudes before and after the treatment in the three groups.Results:There were no significant differences among the three groups before the treatment. Afterward, however, the average FMA-UE, WMFT and BI scores, as well as the upper limb and hand Brunnstrom stages and the average MEP latencies and amplitudes of all the three groups had improved significantly. The combined group′s average results were then significantly better than the other two groups′ averages, except for the upper limb Brunnstrom stages. The increases in MEP amplitude were positively correlated with the increases in FMA-UE scores among the rTMS and the combined group, but there was no significant correlation between them in the control group.Conclusions:The combined application of rPMS and contralateral low frequency rTMS can effectively relieve motor dysfunction in the upper limbs in the early stages after a stroke.

Objective:To explore therapeutic efficacy and mechanism of puerarin(PUE)in treating of ulcerative colitis(UC).Methods:Network pharmacology and molecular docking technique were used to screen and analyze targets of PUE in regulating UC.C57BL/6 mice were given free access to 2.5%DSS aqueous solution for 7 days,and influence of PUE on changes in body weight and disease activity index(DAI)score were subsequently observed.Histopathological alterations of colon tissue were observed by HE staining,changes of goblet cell population in colon tissue were evaluated through Alcian blue staining;expressions of inflammatory factors in colon tissue were detected by qRT-PCR and ELISA.Effect of PUE on MODE-K cell viability and apoptosis were assessed by CCK-8 and flow cytometry.Results:A total of 38 common targets of PUE in modulating UC,such as AKT1,TNF,STAT3,CASP3,HIF1A and etc,mainly involving TNF,IL-17 and PI3K-Akt signaling pathway.In vivo experiments confirmed that PUE ameliorated degree of colon shortening,body weight and DAI scores and reduced inflammatory cell infiltration in mice.Besides,expressions of inflammatory factors in colon,such as TNF-α and IL-1β,were inhibited by PUE.Furthermore,in vitro experiments validated that PUE relieved DSS-induced apoptosis of epithelial cells.Conclusion:PUE alleviates occurrence and development of DSS-induced UC in mice.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the intestine closely associated with immune dysfunction. Colonic lamina propria macrophages are the most abundant population of macrophages in the intestinal mucosa, capable of effectively maintaining and regulating the stability of the intestinal environment. The inflammatory responses mediated by these macrophages play a significant role in the occurrence and development of UC. This article provides a comprehensive review of the roles and mechanisms of two different subtypes of colonic lamina propria macrophages in UC, aiming to provide new insights for the clinical treatment of UC.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the intestine closely associated with immune dysfunction. Colonic lamina propria macrophages are the most abundant population of macrophages in the intestinal mucosa, capable of effectively maintaining and regulating the stability of the intestinal environment. The inflammatory responses mediated by these macrophages play a significant role in the occurrence and development of UC. This article provides a comprehensive review of the roles and mechanisms of two different subtypes of colonic lamina propria macrophages in UC, aiming to provide new insights for the clinical treatment of UC.