Zishen Huoxue decoction (ZSHX) enhances cardiomyocyte viability following hypoxic stress; however, its upstream therapeutic targets remain unclear. Network pharmacology and RNA sequencing analyses revealed that ZSHX target genes were closely associated with mitophagy and apoptosis in the mitochondrial pathway. In vitro, ZSHX inhibited pathological mitochondrial fission following hypoxic stress, regulated FUN14 domain-containing protein 1 (FUNDC1)-related mitophagy, and increased the levels of mitophagy lysosomes and microtubule-associated protein 1 light chain 3 beta II (LC3II)/translocase of outer mitochondrial membrane 20 (TOM20) expression while inhibiting the over-activated mitochondrial unfolded protein response. Additionally, ZSHX regulated the stability of beta-tubulin through Sirtuin 5 (SIRT5) and could modulate FUNDC1-related synergistic mechanisms of mitophagy and unfolded protein response in the mitochondria (UPR^mt) via the SIRT5 and -β-tubulin axis. This targeting pathway may be crucial for cardiomyocytes to resist hypoxia. Collectively, these findings suggest that ZSHX can protect against cardiomyocyte injury via the SIRT5-β-tubulin axis, which may be associated with the synergistic protective mechanism of SIRT5-β-tubulin axis-related mitophagy and UPR^mt on cardiomyocytes.
Mitophagy/drug effects* ; Tubulin/genetics* ; Animals ; Myocytes, Cardiac/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sirtuins/genetics* ; Unfolded Protein Response/drug effects* ; Myocardial Ischemia/genetics* ; Rats ; Humans ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Male

Objective To explore the association between physical activity levels and metabolic dysfunction-associated fatty liver disease(MAFLD)and the modifying effects of different types of obesity.Methods A cross-sectional study was conducted on 19925 participants recruited from the Chengdu sub-cohort of the Southwest China Natural Population Cohort.The participants were recruited between 2018 and 2019.The association between physical activity and MAFLD prevalence was examined using the inverse probability weighting(IPW)method based on the generalized propensity score(GPS).The odds ratios(OR)and the 95％confidence interval(CI)for moderate and vigorous physical activity were calculated using the mild physical activity group as a reference.A restricted cubic spline function was used to model the exposure-response relationship between physical activity and MAFLD risk.The potential modifying effects of obesity types on the association between physical activity and MAFLD were evaluated in male and female populations.Results The prevalence of MAFLD was 17.30％.Compared to those engaging in mild physical activity,individuals participating in vigorous and moderate physical activities had a lower risk of MAFLD,with OR(95％CI)being 0.76(0.67,0.86)and 0.85(0.76,0.94),respectively.The exposure-response relationship showed a nonlinear association between physical activity and MAFLD risks(Pnonlinearity=0.005).The protective effect of physical activity against MAFLD was observed when physical activity reached approximately 20 METs-h/d.However,when physical activity exceeded 70 METs-h/d,no significant effect on MAFLD risk was observed.Among the female population,obesity type significantly modified the association between physical activity and MAFLD(P＜0.05).In females with central obesity,the protective effect of physical activity on MAFLD showed a threshold effect,with the lowest disease risk observed at approximately 25 METs-h/d.However,physical activity exceeding 37.5 METs-h/d showed no statistically significant association with MAFLD risk.In contrast,for females with peripheral obesity,high levels of physical activity had limited effects on reducing MAFLD risks.Conclusion Moderate physical activity can significantly reduce the risk of MAFLD,and the obesity types can modify this association.It is recommended that individuals engage in approximately 20-70 METs-h/d of physical activity.For females with central obesity,physical activity should not exceed 37.5 METs-h/d,while for females with peripheral obesity,it should not exceed 30 METs-h/d.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

ObjectiveTo systematically evaluate the distribution of traditional Chinese medicine（TCM） syndromes of primary osteoporosis（POP） in China by using evidence-based medicine methods， and to understand the distribution law of the syndromes. MethodChina National Knowledge Infrastructure（CNKI）， VIP Chinese Science and Technology Journal Database（VIP）， WanFang Data Knowledge Service Platform（WanFang） and China Biology Medicine（CBM） were searched to obtain representative literature， and each database was searched from the 1994 World Health Organization defined diagnostic criteria for osteoporosis until May 1， 2023. Two researchers independently screened literature according to the criteria， extracted data， and cross-checked them. Meta analysis was conducted using R4.1.3， and subgroup analysis was performed. ResultA total of 56 Chinese papers were included， involving 14 415 patients. After standardized classification of syndromes， 11 articles were excluded， and Meta analysis results of the ultimately included 45 Chinese articles showed that the distribution frequencies of liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome in 12 723 patients were 27%［95% confidence interval（CI） 0.24-0.31］， 32%（95% CI 0.29-0.36）， 36%（95% CI 0.30-0.42）. Subgroup analysis showed that there was a statistically significant difference in the distribution of the three TCM syndromes in the north and south（P<0.05）. In addition， the incidence of TCM syndrome fractures in different types of POP was 15%（95% CI 0.09-0.24） for liver-kidney Yin deficiency syndrome， 20%（95% CI 0.12-0.30） for spleen-kidney Yang deficiency syndrome， and 31%（95% CI 0.25-0.39） for kidney deficiency and blood stasis syndrome. ConclusionThe distribution of syndromes in POP patients is mainly kidney deficiency， accompanied by liver and spleen dysfunction. Liver-kidney Yin deficiency syndrome， spleen-kidney Yang deficiency syndrome and kidney deficiency and blood stasis syndrome are all the main syndromes of POP and osteoporotic fractures， and kidney deficiency and blood stasis syndrome is most closely related to the development of osteoporotic fractures. The reference standards for syndrome determination among the included studies are inconsistent， and in the future， it is necessary to focus on their determination standards to obtain consensus research results， at the same time， conduct large-scale syndrome research to obtain representative research results， providing a basis for clinical practice and research.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective:To explore the assessment value of liver enzyme changes before and after hepatectomy on the prognosis of patients with primary hepatocellular carcinoma(HCC). Methods:A retrospective analysis was conducted on the clinical data of 421 patients with primary HCC who received at the First and Second Affiliated Hospitals of Xi'an Jiaotong University from January 2016 to December 2020.The univariate and multivariate COX regression analyses were used to screen the risk factors affecting the prognosis of patients with primary HCC,and the optimal cut-off value was selected to group the most valuable indicators among them,further analyzing the different factors among subgroups.The Kaplan-Meier method was used to assess the prognosis of the subgroups,and the survival curves were plotted and statistically tested. Results:Multivariate COX regression analysis revealed that Barcelona Clinic Liver Cancer(BCLC)stage,tumor number,alpha-fetoprotein(AFP),the quantitative change of γ-glutamyl transpeptidase(GGT)and total bilirubin(TBIL)before and after surgery were independent risk factors affecting the prognosis of patients with primary HCC(P＜0.01),and there were differences in hepatitis B virus surface antigen(HBsAg),TNM stage,BCLC stage,tumor size,tumor number,tumor differentiation degree,AFP,surgery type,intraoperative bleeding volume,postoperative albumin-bilirubin(ALBI)and white blood cell count between the high and low GGT variation groups(P＜0.05).Kaplan-Meier survival analysis showed that the prognosis of patients with primary HCC between the high and low GGT variation groups was significantly different,with a hazard ratio of 2.603 for mortality and 1.449 for recurrence(both P＜0.01). Conclusion:The quantitative change of GGT before and after hepatectomy has an evaluation value for the prognosis of patients with primary HCC,and the quantitative change of GGT greater than 29.5 is an independent risk factor for the prognosis of patients with primary HCC.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Abstract: Objective To explore the influencing factors of serum HBeAg loss in patients with chronic hepatitis B (CHB) and and provide evidence for effective treatment of CHB. Methods A follow-up cohort of HBeAg-positive CHB patients was established in the the Infectious Diseases Outpatient Clinic of hospital. Regular follow-up and laboratory test indicators were collected to analyze the changes of serum HBeAg in HBeAg-positive CHB patients during the follow-up period. The subjects were divided into the case group (serum HBeAg loss) and the control group (serum HBeAg not loss) according to whether serum HBeAg loss occurred. The baseline data characteristics of the two groups were analyzed and compared, and the influencing factors of serum HBeAg loss were analyzed by Cox univariate and multivariate regression. Results A total of 634 HBeAg-positive CHB patients were enrolled, with a total follow-up of 2 570.01 person-years. Among them, 237 cases of serum HBeAg loss occurred, with the mean follow-up time of 40.92 months, and the rate of HBeAg loss was 9.22/100 person-years. There were significant differences in HBV family history, antiviral therapy, baseline WBC, PLT, ALT, AST, T˗Bil, GGT, AFP, quantitative HBsAg and quantitative HBeAg between serum HBeAg loss group and serum HBeAg not loss group (P<0.05). Cox regression analysis showed that family history of HBV (HR 0.68, 95％CI:0.50-0.92, P=0.012), ALT (HR2.06, 95％CI:1.52-2.79, P<0.001), quantitative HBsAg (HR 0.68, 95％CI:0.48-0.95, P=0.024), quantitative HBeAg (HR 0.48, 95％CI:0.31-0.74, P=0.001) were independent influencing factors for HBeAg loss in HBeAg-positive CHB patients. Conclusions HBeAg-positive CHB patients without family history of HBV, initial ALT≥80 U/L, quantitative HBsAg<1 000 IU/ml, quantitative HBeAg<1 000 C.O.I are more likely to have serum HBeAg loss.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.
Arsenic/analysis* ; Arsenicals/analysis* ; Sulfides ; Arsenic Trioxide ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/analysis* ; Biological Products