Background: Primary dysmenorrhea is the most prevalent gynecological complaint among women of reproductive age, often manifesting as intense cramping pain in the lower abdomen during menstruation. Although pharmaceutical interventions such as nonsteroidal anti-inflammatory drugs (NSAIDs) and oral contraceptives are commonly used to manage symptoms, their temporary effects and frequent side effects, including gastrointestinal issues and hormonal imbalances, limit long-term use. As a result, there is growing interest in complementary and alternative therapies. Huolongguan moxibustion, a traditional Chinese medical technique involving the burning of mugwort (Artemisia vulgaris) near specific acupoints, is believed to enhance energy (qi) flow, promote blood circulation, reduce pain, and restore the balance of body functions. Aim: This study aims to investigate the clinical effectiveness of moxibustion in alleviating menstrual pain and improving overall well-being in patients with primary dysmenorrhea. Additionally, the study seeks to evaluate the feasibility and relevance of applying this traditional technique within contemporary medical practice. Materials and Methods: The study used a non-randomized clinical trial, double-blind, placebo-controlled design with treatment (n=30) and control (n=30) groups. Pain intensity will be assessed using the Visual Analogue Scale (VAS), while quality of life will be measured using the EQ-5D questionnaire. Psychological status, including anxiety and depression levels, will be evaluated using Cox mentrual symptom scale (CMSS). Data will be collected at baseline and post-treatment, followed by statistical analysis to determine treatment efficacy. Result: In the experimental group that received sealed cupping moxibustion therapy, the COX score decreased by approximately 99% after 3 months compared with the baseline value, whereas in the control group it decreased by approximately 27%. In addition, the VAS and EQ-5D-5L scores in the experimental group showed a statistically significant reduction as the duration of treatment increased (P<0.001), indicating that sealed cupping moxibustion therapy effectively reduced pain and related symptoms. Conclusion The results of this study demonstrate that cupping moxibustion therapy significantly reduces pain and associated symptoms in patients with primary dysmenorrhea and improves their quality of life. The therapeutic effect increased with longer treatment duration, and the outcomes in the experimental group were significantly better than those in the control group. Therefore, cupping moxibustion therapy may be considered an effective traditional therapeutic approach for the management of primary dysmenorrhea.

AIM To investigate the effects of Changpu Yujin Decoction(CPYJD)on striatal mitophagy and PINK1/Parkin signaling pathway in a rat model of Tourette syndrome(TS).METHODS Thirty-six SPF male SD rats were randomly assigned to the control group(n=9)and the TS modeling group(n=27).Rats in the modeling group received daily intraperitoneal injections of 3,3'-iminodipropionitrile(IDPN)(300 mg/kg)for 7 consecutive days to establish the TS model.Post-modeling,successfully induced TS rats were re-randomized into model group(no treatment),tiapride group(47.91 mg/kg)and CPYJD group(77.28 g/kg).All groups received their respective interventions via intragastric administration daily for 28 days.Following drug administration,behavioral scores were assessed in each group.Pathological alterations in the striatum were examined using HE staining,while ultrastructural changes were evaluated by transmission electron microscopy(TEM).Neuronal apoptosis was quantified via TUNEL staining,and ROS levels in striatum were measured by ELISA.Co-localization of PINK1 and LC3B was assessed using immunofluorescence(IF).Finally,mRNA and protein expressions of PINK1,Parkin,Beclin-1,P62 and LC3B(LC3B-Ⅱ/Ⅰ ratio)were analyzed by RT-qPCR and Western blot.RESULTS Compared to the control group,the model group demonstrated significantly increased behavioral scores(P＜0.01),elevated neuronal apoptosis rate and higher ROS levels in the striatum(P＜0.01);severe neuronal and mitochondrial damage in the striatum;significantly reduced mRNA and protein expressions of PINK1,Parkin,Beclin-1 and LC3B(LC3B-Ⅱ/Ⅰ ratio)in the striatum(P＜0.01);markedly upregulated P62 mRNA and protein expressions(P＜0.01).Compared to the model group,both the tiapride and CPYJD intervention groups exhibited significantly reduced behavioral scores(P＜0.01);decreased neuronal apoptosis rate and lower ROS levels(P＜0.01);improved pathological alterations in the striatal neurons and mitochondria;increased mRNA and protein expressions of PINK1,Parkin and Beclin-1 in the striatum(P＜0.05,P＜0.01);and decreased P62 mRNA and protein expressions(P＜0.01).Furthermore,the rats in the CPYJD group specifically showed elevated LC3B mRNA level and LC3B-Ⅱ/Ⅰ protein ratio in striatum(P＜0.05,P＜0.01).CONCLUSION The effect of CPYJD intervention in TS rats may involve activation of mitophagy through regulation of the PINK1/Parkin signaling pathway,improving mitochondrial function,reducing ROS levels,and thereby protecting neurons.

Objective To investigate the effects of advanced maternal age(AMA)on synaptic pruning of the hippocampus of offspring rats.Methods Offspring of 3-month-old SD female rats and 3-month-old SD male rats were designated as the appropriate age group(Ctl group),while offspring of 12-month-old SD female rats and 3-month-old SD male rats were assigned to AMA group.Hippocampal tissues from both groups(n=3 per group at each time point)were subjected to Golgi staining on postnatal days(P)7,28,and 60.Dendritic complexity,spine density(DS),and morphology of immature brain neurons at different age stages were compared between the two groups.Results Compared with Ctl group,the dendritic length of AMA group on P7,P28,and P60 was significantly shortened,and the average number of intersections between dendrites and concentric circles on P28 and P60 was also significantly decreased(P<0.05).Compared with Ctl group,the dendritic spine density of AMA group was significantly decreased on P7,P28,and P60.Notably,the density of thin-shaped dendritic spines in AMA group was increased on P7,whereas the densities of stubby-shaped and mushroom-shaped dendritic spines were decreased(P<0.05).On P28 in AMA group,the densities of thin-shaped and mushroom-shaped dendritic spines were significantly increased compared with Ctl group,while the density of stubby-shaped dendritic spines was significantly decreased(P<0.05).The densities of stubby-shaped and mushroom-shaped dendritic spine were markedly lower in AMA group on P60 than those in Ctl group(P<0.05).Conclusions During postnatal brain development periods,there were abnormalities in synaptic pruning in the hippocampal region of the offspring of the AMA,which manifested as reduced dendritic complexity,decreased dendritic spine density,and disorganized dendritic spine morphology.It could be one of the key mechanisms underlying brain dysfunction in the offspring of AMA.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

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 investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Circadian rhythms are core regulatory mechanisms that evolved to align biological functions with the Earth's rotation. These rhythms are conserved across organisms from unicellular life to multicellular species and play essential roles in metabolism, immune responses, and sleep-wake cycle. Circadian disruptions are strongly associated with various diseases. Over the past decades, genetic studies in Drosophila and mice have identified key conserved clock genes and uncovered transcription-translation feedback loops governing circadian regulation. Additionally, rhythmic neurons in the brain integrate complex neural circuits to precisely regulate physiological and behavioral rhythms. This review highlights recent advances in understanding the neuronal circuit mechanisms of rhythmic neurons in the Drosophila brain and discusses future directions for translating circadian rhythm research into chronomedicine and precision therapies.
Animals ; Circadian Rhythm/genetics* ; Neurons/physiology* ; Drosophila/physiology* ; Brain/physiology* ; Nerve Net/physiology*