ObjectiveTo observe the clinical efficacy of electroacupuncture in treatment of simple obesity patients and its effects on the metabolism-inflammation network. MethodsSeventy-two patients with simple obesity were randomly divided into a electroacupuncture group and a sham electroacupuncture group， with 36 patients in each group. In the electroacupuncture group， conventional acupuncture was applied at Zhongwan （CV 12）， bilateral Tianshu （ST 25）， bilateral Daheng （SP15）， Qihai （CV 6）， Guanyuan （CV 4）， bilateral Zusanli （ST 36） and Fenglong （ST 40）. The sham electroacupuncture group used placebo needle at same acupoints as the electroacupuncture group. Both groups were given sparse-dense waves with a frequency of 2/10 Hz， 30 minutes per session， 3 times a week， for a total of 8 weeks of treatment. The changes of human body parameters including body weight， body mass index （BMI）， waist circumference， and body fat percentage （BFP）， metabolic factors including serum fasting blood glucose （FBG）， triglyceride （TG）， total cholesterol （TC）， high density lipoprotein （HDL）， low density lipoprotein （LDL）， leptin， and ghrelin， and inflammatory factors including interleukin-6 （IL-6） and tumor necrosis factor α （TNF-α） were compared before and after treatment. Correlations between changes in leptin， ghrelin and inflammatory factors were further analyzed. ResultsWaist circumference was significantly reduced after treatment in both groups compared with baseline （P＜0.05）， and the post-treatment waist circumference was lower in the electroacupuncture group than in the sham electroacupuncture group （P＜0.05）； body weight， BMI and BFP decreased significantly after treatment compared to pretreatment levels in the electroacupuncture group （P＜0.05）. Serum leptin， IL-6 and TNF-α declined significantly after treatment in both groups versus baseline （P＜0.05）； the electroacupuncture group had lower post-treatment levels of leptin， IL-6 and TNF-α as well as larger pre-post changes than the sham group （P＜0.05）； ghrelin increased markedly after treatment in both groups （P＜0.05）， with higher post-treatment ghrelin and greater pre-post variation observed in the electroacupuncture group （P＜0.05）. In the electroacupuncture group， changes in ghrelin were negatively correlated with IL-6 and positively correlated with TNF-α （P＜0.01）； in the sham electroacupuncture group， ghrelin changes were negatively correlated with both IL-6 and TNF-α， whereas leptin changes were positively correlated with the two inflammatory markers （P＜0.01）. ConclusionElectroacupuncture can effectively improve clinical manifestations， as well as regulate serum metabolic and pro-inflammatory factors in patients with simple obesity， and discrepant correlation patterns of metabolism-inflammation are observed between the two groups.

ObjectiveTo prepare different composite adjuvants based on nano-emulsion(NE) adjuvants, and to investigate their immune effects in influenza vaccine.MethodsNE adjuvant was combined with monophosphoryl lipid A(MPLA) and QS-21 respectively to prepare composite adjuvants, which were then combined with influenza vaccine.Female BALB/c mice were immunized by intramuscular injection on the 0 d and 28 d.After 28 d and 42 d of initial immunization, hemagglutination inhibition(HI), ELISA and flow cytometry were used to evaluate the immune effects.On the 14 d after booster immunization, the female BALB/c mice were intranasally infected with 10 LD_(50)H1N1 influenza virus strain A/Victoria/2570/2019(IVR-215)(H1N1) to evaluate the protective effects against challenge.ResultsThe immunized mice in both two composite adjuvant groups produced high levels of specific IgG antibodies as well as functional HI antibodies.Addition of two kinds of composite adjuvants increased the levels of spleen CD3~+CD4~+and CD3~+CD8~+T cells in mice.The survival rates of mice in composite adjuvant groups were 100% after challenge, and the decline rates of body mass were less than 10%.ConclusionInfluenza vaccine combined with composite adjuvant has higher immunogenicity than that with single adjuvant.This study provides a theoretical basis for the development of influenza vaccine adjuvants and composite adjuvant development.

Objective:To evaluate the risk of developing pulmonary tuberculosis (PTB) among individuals with latent tuberculosis infection (LTBI) in schools and the protective effect of tuberculosis preventive treatment (TPT).Methods:A retrospective cohort study was conducted to collect data on 15 school outbreaks that occurred in Guangdong Province from 2017 to 2021. Baseline information on tuberculin skin test (TST) or interferon-gamma release test (IGRA) was obtained during contact surveys, as well as baseline information such as TPT. The incidence of PTB between 2017 and 2022 was queried using the Chinese Center for Disease Control and Prevention Information System. Poisson regression analysis was used to compare the incidence risk of PTB in the LTBI population under different TST states at baseline. Current cases, new cases and all cases (the sum of the two) were used as dependent variables. Cox regression models were used to analyze various risk factors affecting the risk of PTB in the LTBI population and evaluate the protective effect of TPT.Results:A total of 6 550 contacts were included in this study, of which 409 received TPT. Within 0-3 months after baseline survey, 119 cases were diagnosed as current cases [19.4‰, 119/(6 550-409)]. A total of 17 221.65 person-years of follow-up were conducted, during which 71 new cases were diagnosed (4.1/1 000 person-years, 71/17 221.65). The incidence density of PTB was 47.7/1 000 person-years, 6.6/1 000 person-years, 1.4/1 000 person-years, and 0.9/1 000 person-years, respectively, in TST strong/IGRA positive, TST moderate positive, TST generally positive, and TST and IGRA negative populations. The difference in PTB incidence density was statistically significant [likelihood ratio test LRT=153.16, P<0.001]. TPT was performed for individuals with strong TST or IGRA positivity, and the protection rate could reach 93% ( HR=0.07, 95% CI: 0.02-0.23). Conclusion:After the outbreak of the school epidemic, individuals with strong TST/IGRA positivity have a higher risk of developing PTB in the future. Targeted implementation of TPT can achieve better protection effects. In addition, the risk of developing PTB in individuals with moderate TST positivity is also worth noting.

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.

OBJECTIVE To investigate the effects of the split formulas of Biyuan Heji(BYHJ)on paranasal sinus mucosal in-flammation in rats with acute rhinosinusitis(ARS)based on the pathogenesis of"wind-cold transforming into lung-heat".METHODS Unilateral nasal cavity occlusion combined with nasal dripping of Staphylococcus aureus were performed to establish a rat model of ARS.SD rats were randomly divided into blank,model,BYHJ(wind-cold removal+lung-heat removal),lung-heat removal,wind-cold removal,and positive drug groups,with 6 rats in each group.The rats were treated with the corresponding drugs for 7 d and then the samples were collected.HE staining was used to observe the pathological changes of rat paranasal sinus mucosa tissues,ELISA was employed to determine the levels of interleukin-1β(IL-1β),IL-6,IL-8,IL-9,IL-10,and IL-12 in serum,immunohistochemis-try(IHC)was adopted to measure the protein expression of tumor necrosis factor-α(TNF-α)and intercellular adhesion molecule(ICAM-1)in paranasal sinus mucosa tissues,and Western blot was used to detect the protein expression of phosphorylated p38 mito-gen-activated protein kinase(p38 MAPK),nuclear transcription factor-κB p50(NF-κB p50),and NF-κB p65 in paranasal sinus mucosa tissues.RESULTS The acute sinusitis rat inflammation model was successfully established.Compared with the model group,the water drinking,diet eating,and body weight of rats in the BYHJ group,wind-cold removal,lung-heat removal,and positive drug groups were significantly improved,the aggregation of inflammatory cells in the paranasal sinus mucosal tissue was reduced,and the levels of IL-1β,IL-6,IL-8,IL-9,and IL-12 in the serum were significantly reduced(P<0.01),IL-10 content significantly in-creased(P<0.01),the protein expression of TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 in the paranasal sinus mucosa was significantly decreased(P<0.01).The comparison between various traditional Chinese medicine groups showed that the decrease of IL-1β,IL-6,IL-8,IL-9,IL-12,TNF-α,ICAM-1,p38 MAPK,NF-κB p50,and NF-κB p65 and the increase of IL-10 in the BYHJ group were better than those in the split formula groups(P<0.01),and the lung-heat removal group was better than the wind-cold removal group(P<0.01).CONCLUSION BYHJ and its split formulas can effectively inhibit the inflammatory response in rats with ARS.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Objective:To analyze the trend of infertility disease burden from 1990 to 2019 and predict the age-standardized prevalence rate (ASPR) and age-standardized disability-adjusted life-year (DALY) rate of male and female infertility for 2020—2029, providing a certain reference for the prevention and treatment of infertility diseases.Methods:Based on the Global Burden of Disease 2019, prevalence, ASPR, DALY rate, and age-standardized DALY rate were used to evaluate the global burden of infertility comprehensively. The estimated annual percentage change was used to describe trends in the disease burden of infertility in 21 regions worldwide. The Bayesian age period cohort model was used to predict the ASPR and age-standardized DALY rate for male and female infertility in 204 countries and regions from 2020 to 2029. Sensitivity analysis was performed using the autoregressive integrated moving average model.Results:The prevalence, DALY rate, ASPR and age-standardized DALY rate of global male infertility increased from 319.52 per 100 000,1.82 per 100 000, 2 856.53 per 100 000, and 16.19 per 100 000 in 1990 to 565.30 per 100 000, 3.22 per 100 000, 3 398.53 per 100 000, and 19.36 per 100 000 in 2019, respectively. The prevalence, DALY rate, ASPR, and age-standardized DALY rate of global female infertility increased from 656.67 per 100 000, 3.53 per 100 000, 6 036.36 per 100 000, and 32.27 per 100 000 in 1990 to 1 223.78 per 100 000, 6.59 per 10 000, 7 483.12 per 100 000, and 40.33 per 100 000 in 2019, respectively. The burden of infertility disease was the highest in men and women aged 30-34 years, and the ASPR and age-standardized DALY rates were 4 407.47 per 100 000, 25.08 per 100 000, 10 270.55 per 100 000 and 55.65 per 100 000, respectively. Only in 45-49 years of age, the prevalence of infertility (11.31 per 100 000) and DALY rate (0.06 per 100 000) in women were lower than those in men (15.68 per 100 000 and 0.08 per 100 000). In addition, the burden of infertility was the lowest in high socio-demographic index regions. Cameroon had the highest ASPR (7 652.40 per 100 000) and age-standardized DALY rate (43.94 per 100 000) for male infertility. Chinese women had the highest ASPR (20 402.30 per 100 000) and age-standardized DALY rate (106.16 per 100 000) of infertility. The forecast results show that the burden of male and female infertility diseases will increase in 204 countries and regions from 2020 to 2029.Conclusion:The burden of infertility diseases in men and women increased in 204 countries and regions from 1990 to 2019, and it is predicted that the global burden of infertility diseases will continue to rise in 2020—2029. Preliminary screening of infertility should be carried out as soon as possible, health education should be strengthened and effective prevention and treatment strategies should be formulated.

Objective To investigate the regulatory effect of PU.1 on apoptosis resistance of aging macro-phages under in vitro inflammatory stimulation simulated by lipopolysaccharide(LPS)of Porphyromonas.Methods The expression of PU.1 in periodontitis gingival tissue and normal gingival tissue was analyzed by GEO database.Mouse macrophage cell line RAW264.7 was divided into control group,P.g-LPS group,H2O2 group and PU.1 inhibitor group.mRNA expression of senescence associated secretory phenotype(IL-6,IL-1β,TNF-α)and PU.1 were detected by RT-qPCR;The protein expressions of p21,p16,BAX,caspase-3,Bcl-2,Bcl-xl and PU.1 were detected by Western blot.The number of senescent cells was detected by senescence-associated-galactosidase(SA-β-gal)staining.The apoptosis rate was detected by flow cytometry.Results Compared with control group,the expression of p21,p16 protein and mRNA of IL-6,IL-1β and TNF-α were up-regulated in P.g-LPS group and H2O2 group,the number of senescent cells was increased,the expression of Bcl-2 and Bcl-xl was up-regulated,the expression of BAX and caspase-3 was decreased,and the apoptosis rate was decreased.Meanwhile,the mRNA and protein expression of PU.1 were increased(P<0.05).Compared with P.g-LPS group,mRNA and protein expression of PU.1 in PU.1 inhibitor group were down-regulated,Bcl-2 and Bcl-xl were down-regulated,BAX and caspase-3 expressions were increased,apoptosis rate was increased,the number of senescent cells was decreased,and mRNA levels of IL-6,IL-1β and TNF-α were decreased.The expression of p21 and p16 proteins were down-regulated.(P<0.05).Conclusion Under inflammatory stimulation in vitro,increased expression of PU.1 induced apoptosis resistance of aging macrophages,inhibition of PU.1 promoted apoptosis of aging macrophages,reduced the number of aging macrophages,and down-regulated the secretion of inflammatory factors.