BACKGROUND:Acupuncture is an effective method for lumbar pain in lumbar disc herniation,but its mechanism has not yet been clarified.Factors related to the JAK2/STAT3 signaling pathway regulate the body's inflammatory response and are involved in the process of neuropathic pain. OBJECTIVE:To study the mechanism of acupuncture on lumbar disc herniation in a rat model based on the JAK2/STAT3 signaling pathway. METHODS:Forty Sprague-Dawley rats were randomly divided into four groups:sham operation group,model group,acupuncture group,and acupuncture+agonist group,with 10 rats in each group.Animal models of L5 lumbar disc herniation was constructed through autologous disc cell transplantation in the model group,acupuncture group,and acupuncture+agonist group.Rats in the acupuncture group and the acupuncture+agonist group received acupuncture treatment(Yanglingquan,Shenshu,Huantiao,and Dachangshu acupoints)at 3 days after modeling,and acupuncture treatment was given once a day,20 minutes each,for 15 consecutive days.Rats in the acupuncture+agonist group were injected intrathecally with coumermycin A1,a JAK2 agonist,into the L4/L5 intervertebral space,once a day,20 minutes each,prior to the acupuncture at 6,12,and 18 days after modeling.Paw withdrawal mechanical threshold was detected before and 3,6,9,12,15,and 18 days after modeling.At 18 days after modeling,serum inflammatory factor levels were detected,hematoxylin-eosin staining was performed to observe the morphology of L5-L6 tissues,RT-PCR was performed to detect the expression of JAK2 and STAT3 mRNAs in L5-L6 tissues,and western blot was performed to detect the expression of JAK2,p-JAK2 and p-STAT3 proteins in L5-L6 tissues. RESULTS AND CONCLUSION:The paw withdrawal mechanical thresholds of rats in the model group at different time points after modeling were lower than those in the sham operation group(P<0.05),the paw withdrawal mechanical thresholds of rats in the acupuncture group were higher than those in the model group at 9,12,15,and 18 days after modeling(P<0.05),and the paw withdrawal mechanical thresholds of rats in the acupuncture+agonist group were lower than those in the acupuncture group at 9,12,15,and 18 days after modeling(P<0.05).The levels of interleukin 6,tumor necrosis factor α,neurotransmitter substance P,and brain neuropeptide Y were elevated in the model group compared with the sham operation group(P<0.05);the levels of all four inflammatory factors were reduced in the acupuncture group compared with the model group(P<0.05);and the levels of all four inflammatory factors were elevated in the acupuncture+agonist group compared with the acupuncture group(P<0.05).Hematoxylin-eosin staining showed that lumbar degeneration was obvious in the model group but reduced in the acupuncture group and the acupuncture+agonist group.Moreover,the reduction was more obvious in the acupuncture group compared with the acupuncture+agonist group.The JAK2 and STAT3 mRNA expression as well as the p-JAK2 and p-STAT3 protein expression were elevated in the model group compared with the sham operation group(P<0.05),were decreased in the acupuncture group compared with the model group(P<0.05),and were increased in the acupuncture+agonist group compared with the acupuncture group(P<0.05).To conclude,acupuncture can alleviate inflammation to exert analgesic effects in the rat model of lumbar disc herniation,and its mechanism of action may be related to the inhibition of the JAK2/STAT3 signaling pathway.

Objective: To explore the relationship between sleep characteristics, physical activity patterns, with depressive and anxiety symptoms in college students, so as to provide reference for student mental health promotion. Methods: From September to November 2023, a convenience sampling method was used to select 7 954 college students aged 18-22 years from 9 universities in Shanghai, Hubei, and Jiangxi. Assessments were conducted using the International Physical Activity Questionnaire Short-Form (IPAQ-SF), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and Pittsburgh Sleep Quality Index (PSQI) to evaluate physical activity, depressive and anxiety symptoms, and sleep quality, respectively. Logistic regression analysis was employed to explore the impact of sleep characteristics and physical activity patterns on depressive and anxiety symptoms and their comorbidity among college students. Results: The detection rates for depressive symptoms, anxiety symptoms, and comorbid depression and anxiety symptoms were 25.67%, 35.39%, and 23.15%, respectively. Factors such as gender, grade, household registration, parental education level, annual family income, family structure, and dietary habits were all associated with the detection rates of depressive and anxiety symptoms and their comorbidity (χ2=4.41-118.39, P<0.05). Physical activity patterns, sleep duration, sleep quality, and sleepwake characteristics were also associated with the occurrence of depressive and anxiety symptoms and their comorbidity (χ2=9.66-627.70, P<0.05). Logistic regression analysis showed that college students who stayed up late and slept less than 7 had the highest risk of depressive and anxiety symptoms and their comorbidity (OR=1.93, 1.85, 1.88, P<0.05). Compared to regular physical activity patterns, insufficient physical activity patterns were associated with an increased risk of depressive and anxiety symptoms (all OR=1.18, P<0.05). Further stratified analysis results showed that the risk of depression, anxiety and their comorbidity increased in college students who stayed up late and slept less than 7 h, went to bed before midnight and slept less than 7 h, or went to bed before midnight and slept more than 7 h but did not have sufficient physical activity (P<0.05). Conclusions Sleep characteristics and physical activity patterns significantly affect depressive and anxiety symptoms in college students. Universities should strengthen sleep management and implement flexible physical activity interventions to help students establish healthy lifestyles.

Objective To evaluate the effectiveness of the integrated schistosomiasis control programme in Wuhan City from 2005 to 2023, so as to provide insights into precision control and elimination of schistosomiasis. Methods The integrated measures for schistosomiasis control implemented by health, agriculture, water resources, and forestry departments of Wuhan City, and the epidemiological data of schistosomiasis in Wuhan City were collected from 2005 to 2023, and the prevalence of human schistosomiasis, prevalence of Schistosoma japonicum infections in humans and bovines, areas of S. japonicum-infected snail habitats, areas of snail habitats in inner embankments, and actual areas of snail habitats were retrieved. In addition, the trends in prevalence of schistosomiasis in humans and livestock and snail status were evaluated in Wuhan City from 2005 to 2023 using Mann-Kendall test and a Joinpoint regression model. Results Mann-Kendall test revealed a tendency towards a decline in the prevalence of human schistosomiasis (Z = -4.41, P < 0.01), prevalence of S. japonicum infections in humans (Z = -4.89, P < 0.01) and bovines (Z = -4.50, P < 0.01), areas of S. japonicum-infected snail habitats (Z = -3.91, P < 0.01), areas of snail habitats in inner embankments (Z = -2.28, P = 0.02), and actual areas of snail habitats (Z = -5.95, P < 0.01) in Wuhan City from 2005 to 2023. Joinpoint regression analysis showed an average annual reduction of 8.58% in the prevalence of human schistosomiasis in Wuhan City from 2005 to 2023 [average annual percent change (AAPC) = -8.58%, 95% confidence interval (CI): (-10.02%, -6.65%), P < 0.01], with two joinpoints in 2013 and 2016, respectively, and the tendency towards a decline showed statistical significance during the period from 2013 through 2016 [annual percent change (APC) = -34.41%, 95% CI: (-40.36%, -20.01%), P < 0.01]. The prevalence of S. japonicum human infections appeared an average annual reduction of 51.91% in Wuhan City from 2005 to 2023 [AAPC = -51.91%, 95% CI: (-58.12%, -44.25%), P < 0.01], with two joinpoints in 2014 and 2017, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.17%, 95% CI: (-99.17%, -90.87%), P < 0.01]. The prevalence of S. japonicum infections in bovines appeared an average annual reduction of 53.12% in Wuhan City from 2005 to 2023 [AAPC = -53.12%, 95% CI: (-59.65%, -42.44%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2014 through 2017 [APC = -98.63%, 95% CI: (-99.44%, -90.93%), P < 0.01]. The areas of S. japonicum-infected snail habitats appeared an average annual reduction of 47.09% in Wuhan City from 2005 to 2023 [AAPC = -47.09%, 95% CI: (-52.92%, -38.26%), P < 0.01], with two joinpoints in 2011 and 2014, respectively, and the tendency towards a decline showed statistical significance during the period from 2011 through 2014 [APC = -97.27%, 95% CI: (-98.65%, -88.06%), P < 0.01]. The areas of snail habitats in inner embankments appeared an average annual reduction of 4.45% in Wuhan City from 2005 to 2023 [AAPC = -4.45%, 95% CI: (-5.18%, -3.82%), P < 0.01], with three joinpoints in 2011, 2015 and 2018, respectively, and statistical significance was seen in the tendency towards a decline during the period from 2005 through 2011 [APC = -16.38%, 95% CI: (-20.15%, -14.25%), P < 0.01]. In addition, the actual areas of snail habitats appeared an average annual reduction of 2.65% in Wuhan City from 2005 to 2023 [AAPC = -2.65%, 95% CI: (-2.89%, -2.40%), P < 0.01], with a joinpoint in 2013, and the tendency towards a decline showed statistical significance during the period from 2013 through 2023 [APC = -4.06%, 95% CI: (-4.66%, -3.58%), P < 0.01]. Conclusions The integrated schistosomiasis control programme achieved significant effectiveness in Wuhan City from 2005 to 2023, with a tendency towards a decline in morbidity due to schistosomiasis in humans and livestock and snail status. The integrated schistosomiasis control strategy with emphasis on management of the source of S. japonicum infections should continue to be implemented to consolidate the schistosomiasis control achievements and achieve the goal of schistosomiasis elimination in the city.

Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68⁺ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.

Background The association between occupational physical activity (OPA) and cardiometabolic risk factors remains controversial, potentially due to differences in the associations between OPA and various cardiometabolic indicators, as well as the lack of a clearly defined optimal OPA range for multiple-indicator synergistic benefits. Objective To investigate the relationship between OPA and cardiometabolic risk factors in individuals at high risk of cardiovascular disease (CVD) in Hubei Province, and to explore an optimal OPA range for multi-indicator improvements. Methods Data were derived from the Hubei Province dataset of the China Health Evaluation And Risk Reduction Through Nationwide Teamwork from 2015 to 2023, including 19028 high-risk CVD individuals. OPA (metabolic equivalent·h·d⁻¹, MET·h·d⁻¹) was assessed using the China Kadoorie Biobank physical activity questionnaire, anthropometric measurements (height, weight, waist circumference) and cardiometabolic indicators (blood pressure, fasting blood glucose, lipid profiles) were measured. Multivariate logistic regression was used to analyze the association between logOPA quartiles (Q1-Q4) and abnormal cardiometabolic indicators, while restricted cubic spline (RCS) models were employed to explore their dose-response relationships. Subgroup and interaction analyses were also conducted by gender. Results The median OPA of all participants was 12.86 MET·h·d⁻¹ (male: 14.40 MET·h·d⁻¹, female: 11.14 MET·h·d⁻¹). After adjusting for confounders, compared with the Q1 group, logOPA in the Q4 group was associated with 20% (OR=0.80, 95%CI: 0.72, 0.89), 14% (OR=0.86, 95%CI: 0.78, 0.96), and 13% (OR=0.87, 95%CI: 0.79, 0.95) reduction in the risk of abdominal obesity, low high-density lipoprotein cholesterol (HDL-C), and metabolic syndrome (MS), respectively, and 33% (OR=1.33, 95%CI: 1.18, 1.49), 33% (OR=1.33, 95%CI: 1.18, 1.50), and 38% (OR=1.38, 95%CI: 1.21, 1.57) increase in the risk of high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), and high non-HDL-C, respectively. Similar trends were observed in males and females, with significant positive associations of logOPA with high TC and high non-HDL-C in males (P_interaction<0.05). The risk of low HDL-C decreased rapidly when logOPA was more than 2.213 (OPA>9.14 MET·h·d⁻¹), showing an inverted L-shaped trend. The risk of high TC, high LDL-C, and high non-HDL-C increased beyond logOPA thresholds of 3.244, 2.476, and 3.377 (OPA >25.64, 11.89, and 29.28 MET·h·d⁻¹), respectively, showing a J-shaped trend. However, logOPA exhibited a U-shaped nonlinear dose-response relationship with blood pressure and fasting blood glucose abnormalities (P_non-linear<0.05) , with minimal risks at logOPA 2.969 and 2.372 (OPA of 19.47 and 10.72 MET·h·d⁻¹). Conclusion OPA exhibits heterogeneous dose-response patterns across cardiometabolic indicators. Integrating the inverted L-, J-, and U-shaped association patterns, we suggest an optimal OPA range of 9.14−25.64 MET·h·d⁻¹ for multiple cardiometabolic indicators in total individuals at high-risk of CVD, with ranges of 9.61−31.34 MET·h·d⁻¹ for males and 8.97−22.87 MET·h·d⁻¹ for females. These findings provide critical evidence for developing OPA interventions strategies targeting high-risk population for CVD.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis （CASBP）. MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022， and the patients were randomly divided into optimized treatment group and traditional treatment group， with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model， and those in the traditional treatment group received ceftazidime for initial treatment， with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment， cure rate on day 5， and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.0% vs 60.0%， χ²=5.094， P=0.024）， while there was no significant difference in the cure rate on day 5 between the two groups （80.0% vs 56.6%， χ²=3.309， P=0.069）. As for the patients who received ceftazidime for initial treatment， the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.9% vs 60.0%， χ²=4.341， P=0.037）， while there was no significant difference in the cure rate on day 5 between the two groups （83.3% vs 56.0%， χ²=2.425， P=0.119）. There was no significant difference in 30-day mortality rate between the two groups （8.0% vs 20.0%， χ²=0.664， P=0.415）. For all patients， there was a significant association between response of initial treatment and cure on day 5 （odds ratio ［OR］=9.643， 95% confidence interval ［CI］： 2.292‍ — ‍40.564） and between cure on day 5 and 30-day mortality （OR=0.138， 95%CI： 0.023‍ — ‍0.813）. ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP.

Traditional Chinese medicine can regulate the hypoxia-inducible factor-1α(HIF-1α)signalling pathway and slow down tumour progression mainly by inhibiting tumour angiogenesis,glycolysis,epithelial mesenchymal transition and other pathological processes.This paper,starting from HIF-1α and related factors,reviews its pathological mechanism in tumours and the research of traditional Chinese medicine interventions with the aim of providing theoretical references for the treatment of tumours with traditional Chinese medicine.

Objective To investigate the protective effects of melatonin(MT)on early embryo in vitro development of mice after exposure to benzophenone-3(BP-3).Methods Fertilized mouse oocytes at the synge-neic stage were cultured in KSOM culture medium,0.8 μmol/L BP-3 culture medium,and 1×10-7 mol/L MT + 0.8 μmol/L BP-3 mixed culture medium,respectively.The rescue effect of MT on the early embryos developmental potential of BP-3-exposed mice in vitro was explored by detecting the blastocyst rate,gene transcription level,protein expression level,and the degree of DNA damage in the three groups of embryos.Results MT improved the developmental potential of mouse embryos exposed to BP-3 in vitro.Compared with the control group,MT treatment significantly increased the protein expression of ATP5A and ATP5B and decreased the DNA damage(P<0.05).Furthermore,the transcription levels of antioxidant gene Gpx1 and pluripotency related genes Pou5f1 and Cdx2 were significantly up-regulated in MT-treated blastocysts,and the expression of pro-apoptotic gene Bax was decreased.Compared with the control group,BP-3 treatment enhanced the signal intensity of γ-H2AX in blastocysts(P<0.05),while adding MT could effectively alleviate DSBs(P<0.05).Conclusion The physiological concentration of BP-3 exposure has reproductive toxicity,but the addition of appropriate con-centration of MT could significantly improve the in vitro developmental potential and quality of BP-3-exposed early embryos.

Objective:To observe any effect of repetitive transcranial magnetic stimulation (rTMS) on sleep disorders among children with cerebral palsy (CP).Methods:A total of 102 children with CP and disordered sleep were randomly divided into an experimental group and a control group, each of 51. All were given routine rehabilitation and sleep health education, but the experimental group additionally received rTMS for two weeks. The polysomnography (PSG) results of the two groups were recorded and analyzed.Results:The PSG parameters had improved greatly in both groups after the treatment. The percentage of N2 sleep (depth of sleep during light sleep) in the severe cerebral palsy group and of N3 sleep (depth of sleep during deep sleep) in the moderate cerebral palsy group had increased significantly more than in the mild cerebral palsy group, on average. After the intervention the percentages of N2 and N3 in those with mixed cerebral palsy and of N3 in those with involuntary motor cerebral palsy had increased significantly more than in those with spastic cerebral palsy, on average.Conclusion:rTMS treatment can improve the sleep disorders of children with cerebral palsy, especially N2 sleep among children with moderate to severe cerebral palsy, N3 sleep in cases of mixed or dyskinetic CP.