Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective: To investigate the knowledge and behaviors related to hepatitis B prevention and control among carriers of hepatitis B surface antigen (HBsAg), so as to provide the basis for conducting health education and interventions for HBsAg carriers. Methods: Based on the seroepidemiological survey of hepatitis B among individuals aged 1 to 69 years in Shaanxi Province, HBsAg carriers were selected as the study subjects. Basic information, knowledge and behaviors about hepatitis B prevention and control were collected through questionnaire surveys. The awareness of hepatitis B prevention and control knowledge and related behaviors among HBsAg carriers were analyzed. Results: A total of 107 HBsAg carriers were enrolled, including 52 males (48.60%) and 55 females (51.40%), and had a median age of 47.04 (interquartile range, 19.78) years. The awareness of hepatitis B prevention and control knowledge ranged from 56.07% to 87.85% among HBsAg carriers, with the highest awareness for "hepatitis B vaccination can effectively prevent hepatitis B "(87.85%), and the lowest awareness for "sharing meals with HBsAg carriers or hepatitis B patients will not lead to infection" (56.07%) and "hepatitis B can be treated with antiviral drugs" (61.68%). The proportions of those who did not seek medical consultation, undergo regular check-ups, or receive treatment were relatively high, at 65.42%, 72.90% and 77.57%, respectively. Conclusions The awareness of hepatitis B transmission routes and treatment-related knowledge among HBsAg carriers is relatively low, and their medical-seeking behaviors are relatively passive. There is a need to enhance the dissemination of hepatitis B prevention and control knowledge, improve medical-seeking behaviors, and reduce the risk of hepatitis B virus transmission.

Objective:To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination.Methods:From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed.Results:All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion:The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

Objective:To study the effect of adipose tissue derived extracellular vesicles (AT-EVs) on nerve regeneration and functional reinnervation after sciatic nerve injury (SNI) in rat.Methods:From April 2023 to April 2024, the experiment was completed by the Department of Orthopaedics, the First Affiliated Hospital of Zhengzhou University in the key laboratory of the School of Medical Sciences, Zhengzhou University. AT-EVs were isolated and extracted from subcutaneous adipose tissue of 12 healthy male SD rats using ultracentrifugation. The morphology, size and distribution of AT-EVs were characterised via transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The effect of AT-EVs on the proliferation ability of pheochromocytoma cells of rat (PC12) and rat Schwann cells (RSC 96) were detected by cell proliferation assay. Twenty-four healthy male SD rats were randomly divided into 3 groups with 8 rats per group, including a sham group, a SNI group and an AT-EVs treatment group. Right sciatic nerves of rat models in sham group were exposed without injury. For the rat models in SNI group and AT-EVs treatment group, right sciatic nerves were injected with phosphate buffered solution (PBS) and AT-EVs under the epineurium of the nerve respectively following sciatic nerve crush. At 28 days after surgery, Sciatic function index (SFI) and pace analysis was performed. Then, rats in all groups were sacrificed, and bilateral gastrocnemius muscles were collected to measure the muscle wet weight ratio. The right sciatic nerves were removed for further exploration of nerve regeneration. The histopathological changes and axon arrangement of sciatic nerve were evaluated by Hematein Eosin (HE) staining and Masson staining. The regeneration efficiency of Myelin forming protein (MBP) and Neuronal marker [β-tubulin (Tuj-1)] were analysed by immunofluorescence staining of sciatic nerve. Statistical analysis was conducted using GraphPad Prism 8.0. P<0.05 were considered statistically significant. Results:The results of TEM and NTA revealed that AT-EVs exhibited a typical disc-shaped bilayer membrane structure with a predominant particle size of 184.5 nm. AT-EVs significantly enhanced the proliferation ability of PC12 and RSC96, and the difference was statistically significant ( P<0.05). At 28 days after surgery, the SFI and muscle wet weight ratio were higher in the AT-EVs treatment group compared to the SNI group, and the difference was statistically significant ( P<0.05). Axons in AT-EVs treatment group were arranged more closely and orderly than those in SNI group at 28 days after surgery, and there were less axon disintegration and vacuolation caused by injury. The immunofluorescence assay indicated that the MBP and Tuj-1 fluorescence intensity in AT-EVs treatment group was significantly higher than those in the SNI group, and the difference was statistically significant ( P<0.05). Conclusion:AT-EVs can enhance the proliferation ability of PC12 and RSC96 to promote axon regeneration and functional reinnervation following SNI.

Objective:To estimate the incidence of Bordetella pertussis（ Bp）infection by analyzing the seroepidemiological characteristics of pertussis in healthy people aged 1-14 years in Shaanxi Province in 2017. Methods:A stratified random sampling method was used to select healthy people aged 1-14 years from 30 county-level disease surveillance sites in 10 cities of Shaanxi Province in 2017. Serum IgG antibodies against pertussis toxin（PT-IgG）were quantitatively detected by ELISA. The incidence of Bp infection within one year（PT-IgG≥100 IU/ml）and the geometric mean concentration（GMC）of PT-IgG were analyzed. Statistical analysis was performed using Mann-Whitney U test，Kruskal-Wallis test，or Jonckheere-Terpstra test. Results:A total of 1 777 subjects were included. The incidence of Bp infection within one year was 0.84%（15/1 777）and the GMC of PT-IgG was 5.70 IU/ml. The incidence of Bp infection within one year in different age groups ranged from 0 to 3.06%（3/98），and the GMC of PT-IgG was between 2.99 IU/ml and 9.29 IU/ml. People aged 12-14 years showed higher incidence of Bp infection within one year. The estimated incidence of Bp infection in people aged 5-14 years was 6 639.97/100 000，with the lowest incidence in people aged 5-6 years（2 016.85/100 000）and the highest in people aged 13-14 years（15 425.95/100 000）. The estimated incidence of Bp infection increased with age（ χ 2trend=12 090， P<0.01）. Conclusions:The actual incidence of Bp infection in healthy people aged 1-14 years in Shaanxi Province is high，and the duration of antibody responses to vaccination is limited. Children and adolescents are high-risk groups for pertussis，and attention should be paid to people aged 12-14 years. It is recommended to strengthen the routine monitoring of pertussis in order to better adjust and optimize the immunization strategy.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

ObjectiveTo observe the effect of Zishen Tiaogan prescription on the oxidative stress injury in the rat model of diminished ovarian reserve （DOR） and explore the role of the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty-eight female SD rats were randomly assigned into a normal group （n=12） and a modeling group （n=36）. The rats in the modeling group received subcutaneous injection of galactose （350 mg·kg^-1） combined with immobilization stress daily. After 28 days of modeling， 6 rats in the normal group and 6 rats in the modeling group were sacrificed to examine the modeling results. The successfully modeled rats were assigned into model， estradiol valerate （0.09 mg·kg^-1）， and low-， medium-， and high-dose （6.39， 12.78， 25.56 g·kg^-1， respectively） Zishen Tiaogan prescription groups. The intervention lasted for 4 weeks with 6 animals per group. Hematoxylin-eosin staining was used to observe the estrous cycle and the pathological changes in the ovarian tissue. The ovarian index was calculated. Enzyme-linked immunosorbent assay was employed to measure the serum levels of sex hormones and oxidative stress-related indexes. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of Nrf2， Keap1 and HO-1 in the ovarian tissue. The positive expression of superoxide dismutase 2 （SOD2） in the ovarian tissue was detected by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group showed reduced follicles in the ovary， loose arrangement of the follicle granule layer， declined levels of anti-Mullerian hormone （AMH） and estradiol （E₂） in the serum， elevated levels of luteinizing hormone （LH） and follicle-stimulating hormone （FSH） （P<0.01）， lowered levels of superoxide dismutase （SOD）， catalase （CAT）， and glutathione （GSH） （P<0.01）， and increased accumulation of malondialdehyde （MDA） （P<0.01）. In addition， the modeling led to up-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 and HO-1 protein was significantly decreased （P<0.01）， the mRNA expression of Nrf2 was significantly decreased （P<0.05）， the mRNA expression of HO-1 was significantly decreased （P<0.01）， in the ovarian tissue. Compared with model group， the estradiol valerate and low-， medium-， and high-dose Zishen Tiaogan prescription groups showed increases in the ovarian index （P<0.01） and serum E₂ and AMH levels （P<0.01）， declined levels of FSH and LH （P<0.01）， increased follicles in the ovary， elevated levels of SOD， CAT， and GSH， and reduced accumulation of MDA （P<0.05， P<0.01）. Furthermore， these groups showcased down-regulated protein and mRNA levels of Keap1 （P<0.01）， the expression of Nrf2 protein was significantly increased （P<0.01）， the expression level of HO-1 protein was increased （P<0.05，P<0.01）， and increased positive expression of SOD2 （P<0.01）. ConclusionZishen Tiaogan prescription can regulate the serum levels of hormones， down-regulate the expression of Keap1， up-regulate the expression of Nrf2， HO-1， and SOD2， enhance the antioxidant capacity， and reduce the peroxidation damage in the ovarian tissue to improve the ovarian reserve function in the rat model of DOR. High-dose Zishen Tiaogan prescription demonstrated the best effect and the mechanism is associated with the regulation of the Keap1/Nrf2/HO-1 pathway.

Objective To investigate the serum diphtheria antibody levels in healthy people aged 1-59 years old in Shaanxi Province.Methods A stratified random sampling method was used to select healthy people aged 1-59 years old from 30 county-level disease surveillance sites in 10 cities of Shaanxi province from November to December 2017.Diphtheria IgG antibody was detected by enzyme-linked immunosorbent assay(ELISA),and the positive rate(IgG≥0.01 IU/mL)and mean geometric concentration(GMC)of diphtheria IgG antibody were analyzed.Results A total of 6 439 subjects completed laboratory testing.The positive rate and GMC of diphtheria IgG antibody were 85.79%and 0.035(0.034-0.036)IU/mL,respectively.The GMC and the positive rate of diphtheria IgG antibody were higher in males than those in females(P＜0.01).The positive rate of diphtheria IgG antibody in different cities was 65.25%-98.23%,and the GMC was 0.021(0.018-0.024)IU/mL-0.046(0.037-0.055)IU/mL,the difference between the groups was statistically significant(P＜0.01).The GMC of the group with DCV immunization history,the group without DCV immunization history and the group with unknown DCV immunization history were 0.097(0.090-0.105),0.018(0.018-0.019)and 0.027(0.026-0.028)IU/mL,respectively,and the positive rates of diphtheria IgG antibody were 92.74%,80.18%and 85.44%,respectively.There were significant differences between the three groups(P＜0.01).Among the 9 age groups,the group with the lowest positive rate of diphtheria IgG antibody was the 40-49 age group(78.39%),and the highest was in the 1-2 age group(95.77%),which decreased with age(χ2=200.612,P＜0.01).It showed a downward trend with age(χ2=200.612,P＜0.01).The lowest GMC(IU/mL)was in the 40-49 age group[0.017(0.016-0.017)],and the highest was in the 7-9 age group[0.190(0.162-0.226)],showing a downward trend with increasing age(P＜0.01).After the whole course of vaccination,the positive rate of diphtheria IgG antibody and the interval between the last dose of vaccination showed a downward trend(P＜0.01).Conclusion The diphtheria immune barrier in whole population has been established in Shaanxi province,but the positive rate of diphtheria antibody and GMC in healthy people aged 1-59 years old show a downward trend with age.

In recent years, the incidence of infertility has been steadily increasing. Obesity, recognized as a chronic inflammatory condition, can not only lead to various chronic diseases such as hypertension and diabetes, but also adversely affects female reproductive health,including rare ovulation, anovulation, menstrual irregularities, and even infertility. The reproductive outcomes of overweight/obese women are not optimistic even among people undergoing assisted reproductive technology (ART).However, the mechanisms of overweight and obesity on ART outcomes remain poorly understood. This review aims to summarize current evidence on the impact of overweight and obesity on ART outcomes in women and explore the potential mechanisms.