Exercise fatigue is a complex physiological and psychological phenomenon that includes peripheral fatigue in the muscles and central fatigue in the brain. Peripheral fatigue refers to the loss of force caused at the distal end of the neuromuscular junction, whereas central fatigue involves decreased motor output from the primary motor cortex, which is associated with modulations at anatomical sites proximal to nerves that innervate skeletal muscle. The central regulatory failure reflects a progressive decline in the central nervous system’s capacity to recruit motor units during sustained physical activity. Emerging evidence highlights the critical involvement of central neurochemical regulation in fatigue development, particularly through neurotransmitter-mediated modulation. Alterations in neurotransmitter release and receptor activity could influence excitatory and inhibitory signal pathways, thus modulating the perception of fatigue and exercise performance. Increased serotonin (5-HT) could increase perception of effort and lethargy, reduce motor drive to continue exercising, and contribute to exercise fatigue. Decreased dopamine (DA) and noradrenaline (NE) neurotransmission can negatively impact arousal, mood, motivation, and reward mechanisms and impair exercise performance. Furthermore, the serotonergic and dopaminergic systems interact with each other; a low 5-HT/DA ratio enhances motor motivation and improves performance, and a high 5-HT/DA ratio heightens fatigue perception and leads to decreased performance. The expression and activity of neurotransmitter receptors would be changed during prolonged exercise to fatigue, affecting the transmission of nerve signals. Prolonged high-intensity exercise causes excess 5-HT to overflow from the synaptic cleft to the axonal initial segment and activates the 5-HT1A receptor, thereby inhibiting the action potential of motor neurons and affecting the recruitment of motor units. During exercise to fatigue, the DA secretion is decreased, which blocks the binding of DA to D1 receptor in the caudate putamen and inhibits the activation of the direct pathway of the basal ganglia to suppress movement, meanwhile the binding of DA to D2 receptor is restrained in the caudate putamen, which activates the indirect pathway of the basal ganglia to influence motivation. Furthermore, other neurotransmitters and their receptors, such as adenosine (ADO), glutamic acid (Glu), and γ‑aminobutyric acid (GABA) also play important roles in regulating neurotransmitter balance and fatigue. The occurrence of central fatigue is not the result of the action of a single neurotransmitter system, but a comprehensive manifestation of the interaction between multiple neurotransmitters. This review explores the important role of neurotransmitters and their receptors in central motor fatigue, reveals the dynamic changes of different neurotransmitters such as 5-HT, DA, NE, and ADO during exercise, and summarizes the mechanisms by which these neurotransmitters and their receptors regulate fatigue perception and exercise performance through complex interactions. Besides, this study presents pharmacological evidence that drugs such as agonists, antagonists, and reuptake inhibitors could affect exercise performance by regulating the metabolic changes of neurotransmitters. Recently, emerging interventions such as dietary bioactive components intake and transcranial electrical stimulation may provide new ideas and strategies for the prevention and alleviation of exercise fatigue by regulating neurotransmitter levels and receptor activity. Overall, this work offers new theoretical insights into the understanding of exercise central fatigue, and future research should further investigate the relationship between neurotransmitters and their receptors and exercise fatigue.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

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OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To construct and identify an organoid model of human placental site trophoblastic tumor(PSTT).Methods The tumor cells were obtained by digesting and separating the PSTT tissues and then embedded in Matrigel.The organoids were cultured in the specific organoid medium.The histological morphology of the organoid model was observed by HE staining and the expression levels of the PSTT specific markers[human placental prolactin(HPL),human leukocyte antigen-G(HLA-G)and placental alkaline phosphatase(PLAP)]were detected by immunohistochemistry and immunofluorescence,so as to evaluate the consistency between the organoid model and the PSTT tissue.Meanwhile,the morphology and forming efficiency of the constructed model were observed under a microscope after primary culture,passage generation and cryopreservation to evaluate its potential application as an organoid model in basic and clinical translational research of PSTT.Results The constructed organoid model could proliferate stably,growing from small microspheres into compact solid spheres or spheres with follicle-like structures,and could passage after fully grown in 7-10 days.The cell state remained stable after passage,frozen storage and recovery.HE staining showed that the morphology of the cells in the organoids was similar to that of the primary PSTT tumor cells,and immunofluorescence staining showed that the organoids highly expressed HLA-G and lowly expressed β-HCG,indicating that the constructed organoid model mainly contained intermediate trophoblast.Conclusion The adult-derived PSTT organoid(ADPO)models were successfully established.

Occupational exposure to ionizing radiation represents a critical factor contributing to health risks in workplaces. Previous experimental and clinical studies have demonstrated that ionizing radiation affects human health. Therefore, scientific assessment of health risk caused by ionizing radiation and effective protection against ionizing radiation are of great importance to formulate the preventive interventions against occupational exposure to ionizing radiation. This review summarizes the advances in the research on health effects, health risk assessment methods, and protective interventions of ionizing radiation. We call for research on the health effects of low-dose radiation, individual difference, and optimization of preventive strategies. In addition, improved mechanisms of health monitoring, periodical healthy examinations, and monitoring of radiation doses should be implemented. Moreover, strict compliance to operating procedures and occupational preventive interventions are recommended. These measures aim to minimize the potential harmlessness of occupational exposure to ionizing radiation, thereby safeguarding the health and safety of individuals exposed to ionizing radiation.

Objective:To identify additional loci associated with depression and the hippocampus (HIP) through genome-wide association study.Methods:The depression-related genome-wide association study (GWAS) meta summary data was downloaded from the official website of the Psychiatric Genomics Consortium, which had involved 170 756 cases and 329 443 controls. The left and right hippocampal volume GWAS data sets were downloaded from the UK Biobank, which involved 33 224 participants. The conditional false discovery rate (condFDR) was used to identify novel genetic loci for depression and left and right hippocampal volumes, and a conjunctional false discovery rate (conjFDR) was used to evaluate the enrichment of pleiotropic loci between depression and left and right hippocampal volumes.Results:Respectively, 7, 13, and 12 new loci have been associated with depression, left hippocampal volume and right hippocampal volume, with a significant threshold of condFDR < 0.01. A site of rs1267073 locus was found to be shared by the depression and right hippocampal volume with a threshold of conjFDR < 0.01.Conclusion:Above findings have provided more insights into the genetic mechanisms underlying the volume of hippocampus and the risk for depression. The results may also provide evidence for future clinical trials for treating depression.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To compare the efficacy of renal proximal renal artery denervation(pRDN)and full-length renal artery denervation(fRDN)for treatment of hypertension.Methods Fifty-six hypertensive patients were enrolled and randomly assigned to full-length renal artery denervation group(n=25)and proximal renal artery denervation group(n=31).After the procedure,24-hour ambulatory blood pressure monitoring(24 h-ABPM)at 6 months and office blood pressure at 12 months was recorded for statistical analysis.Results The blood pressure at follow-up reduced significantly in both groups,while there was no significant difference between groups.The baseline office blood pressure in fRDN group and pRDN group was(180±15)/(104±10)mmHg and(180±12)/(103±8)mmHg,respectively,which decreased to(142±9)/(82±7)mmHg and(143±10)/(83±6)mmHg at 12 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).The baseline 24 h-ABPM in the two groups was(162±13)/(95±8)mmHg and(160±12)/(94±8)mmHg,respectively,which decreased to(142±11)/(83±7)mmHg and(141±8)/(81±7)mmHg at 6 months postoperatively(P＜0.001 within groups and P＞0.05 between groups).However,there was no significant difference in the reduction of office blood pressure and ambulatory blood pressure between the two groups.No treatment-related adverse events were observed.Conclusions pRDN has similar antihypertensive effect to fRDN.

Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P＜0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P＞0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.