Recently, male reproductive health has attracted extensive attention, with the adverse effects of circadian disruption on male fertility gradually gaining recognition. However, the mechanism by which circadian disruption leads to damage to male reproductive system remains unclear. In this review, we first summarized the dual regulatory roles of circadian clock genes on the male reproductive system: (1) circadian regulation of testosterone synthesis via the hypothalamic-pituitary-testicular (HPT) and hypothalamic-pituitary-adrenal (HPA) axes; (2) non-circadian regulation of spermatogenesis. Next, we further listed the possible mechanisms by which circadian disruption impairs male fertility, including interference with the oscillatory function of the reproductive system, i.e., synchronization of the HPT axis, crosstalk between the HPT axis and the HPA axis, as well as direct damage to germ cells by disturbing the non-oscillatory function of the reproductive system. Future research using spatiotemporal omics, epigenomic assays, and neural circuit mapping in studying the male reproductive system may provide new clues to systematically unravel the mechanisms by which circadian disruption affects male reproductive system through circadian clock genes.
Male ; Humans ; Animals ; Circadian Clocks/physiology* ; Hypothalamo-Hypophyseal System/physiology* ; Circadian Rhythm/genetics* ; Spermatogenesis/physiology* ; Pituitary-Adrenal System/physiology* ; Testis/physiology* ; Testosterone/biosynthesis* ; CLOCK Proteins ; Infertility, Male/physiopathology*

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

Objective To explore the characteristic changes in white matter microstructure in Parkinson's disease(PD)patients via automated fiber quantification(AFQ)technology,providing a basis for the identification and diagnosis of PD,and to analyze the feasibility of combining the AFQ method with support vector machine(SVM)in the diagnosis of PD.Methods Forty patients with primary PD(PD group)and 20 healthy controls(HC)(HC group)were prospectively selected.The AFQ technology was applied for white matter fiber tract analysis.Statistical analyses were performed using FSL(v6.0)software and SPSS 27.0 software.Independent-sample t-tests were conducted for comparisons between groups in AFQ analysis.The AFQ method was used to analyze the relationship between diffusion tensor imaging(DTI)parameters and Montreal Cognitive Assessment(MoCA)scores.Results(1)The results of AFQ analysis revealed that compared with the HC group,the PD group exhibited significantly lower fractional anisotropy(FA)values in the right cingulum bundle,left cingulum bundle hippocampus,and left uncinate fasciculus,with no differences in the FA values of the remaining 17 fiber tracts.Moreover,PD group demonstrated higher mean diffusivity(MD)values in the left cingulum bundle,left cingulum bundle hippocampus,left inferior frontal occipital fasciculus,left inferior longitudinal fasciculus,left superior longitudinal fasciculus,and left uncinate fasciculus.These differences were statistically significant(P<0.05),while no significant differences were found in the MD values of the remaining 14 fiber tracts.Furthermore,the MD values of the left inferior frontal occipital fasciculus,and left inferior longitudinal fasciculus were negatively correlated with the MoCA scores.(2)The classification results of SVM showed that the best results were achieved when combining the differential nodes of FA and MD as classification features,with an area under the curve(AUC)of 0.922,an accuracy of 84.81%,a sensitivity of 87.50%,and a specificity of 82.05%.Conclusion The DTI parameters in PD patients can serve as potential biomarkers for diagnosis.The AFQ methods provides an effective approach for detecting alterations white matter tract integrity,offering important insights for the identification and diagnosis of PD.The best results are achieved when combining the differential nodes of FA and MD as classification features.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

Objective To explore the characteristic changes in white matter microstructure in Parkinson's disease(PD)patients via automated fiber quantification(AFQ)technology,providing a basis for the identification and diagnosis of PD,and to analyze the feasibility of combining the AFQ method with support vector machine(SVM)in the diagnosis of PD.Methods Forty patients with primary PD(PD group)and 20 healthy controls(HC)(HC group)were prospectively selected.The AFQ technology was applied for white matter fiber tract analysis.Statistical analyses were performed using FSL(v6.0)software and SPSS 27.0 software.Independent-sample t-tests were conducted for comparisons between groups in AFQ analysis.The AFQ method was used to analyze the relationship between diffusion tensor imaging(DTI)parameters and Montreal Cognitive Assessment(MoCA)scores.Results(1)The results of AFQ analysis revealed that compared with the HC group,the PD group exhibited significantly lower fractional anisotropy(FA)values in the right cingulum bundle,left cingulum bundle hippocampus,and left uncinate fasciculus,with no differences in the FA values of the remaining 17 fiber tracts.Moreover,PD group demonstrated higher mean diffusivity(MD)values in the left cingulum bundle,left cingulum bundle hippocampus,left inferior frontal occipital fasciculus,left inferior longitudinal fasciculus,left superior longitudinal fasciculus,and left uncinate fasciculus.These differences were statistically significant(P<0.05),while no significant differences were found in the MD values of the remaining 14 fiber tracts.Furthermore,the MD values of the left inferior frontal occipital fasciculus,and left inferior longitudinal fasciculus were negatively correlated with the MoCA scores.(2)The classification results of SVM showed that the best results were achieved when combining the differential nodes of FA and MD as classification features,with an area under the curve(AUC)of 0.922,an accuracy of 84.81%,a sensitivity of 87.50%,and a specificity of 82.05%.Conclusion The DTI parameters in PD patients can serve as potential biomarkers for diagnosis.The AFQ methods provides an effective approach for detecting alterations white matter tract integrity,offering important insights for the identification and diagnosis of PD.The best results are achieved when combining the differential nodes of FA and MD as classification features.

Objective:To investigate the clinical characteristics and survival analysis of myelodysplastic syndromes(MDS)with RUNX1 gene mutation.Methods:Clinical data of 177 newly diagnosed MDS patients admitted to the Department of Hematology,the Second Affiliated Hospital of Air Force Military Medical University from October 1,2015 to October 31,2022 were retrospectively analyzed.Gene mutation detection was performed by second-generation sequencing technology,and clinical characteristics and prognosis of patients with RUNX1 gene mutation were analyzed.Results:A total of 30 cases(16.95％)of RUNX1 gene mutations were detected,including 15 missense mutations(50.0％),9 frameshift deletion mutations(30.0％),4 splice site mutations(13.3％),1 insertion mutation(3.3％),and 1 nonsense mutation(3.3％).Patients with RUNX1 mutations had a median age of 68.5 years at diagnosis(range:62.25-78.50 years old).There were no significantly differences between RUNX1 mutations and wild type patients in age distribution,gender,peripheral blood white blood cell count,hemoglobin level,bone marrow and peripheral blood blasts ratio,IPSS-R cytogenetics,IPSS-R stage,etc.(P＞0.05).However,there were statistically significant differences in platelet count and whether complicated karyotype.Compared with patients without RUNX1 gene mutation,patients with RUNX1 gene mutation had lower platelet count(P=0.018),and were less likely to have complicated karyotype at initial diagnosis(P=0.01).Cox proportional hazards model analysis showed that when other co variates remained unchanged,the higher the platelet count,the better the survival of patients(HR=0.995,95％CI:0.990-0.999,P=0.036);In the IPSS-M prognostic stratification,keeping other covariates unchanged,the risk of progression or death of myelodysplastic syndrome was significantly lower in the medium to high-risk and low-risk groups compared with the high-risk group(HR=0.149,95％CI:0.031-0.721,P=0.018;HR=0.026,95％CI:0.003-0.234,P=0.001).Survival analysis showed that MDS patients with RUNX1 gene mutation had worse overall survival time(P＜0.001).Patients with RUNX1 mutation had worse OS than non-mutation patients in the early WHO group.RUNX1 mutation and IPSS-M risk stratification mean OS and mean LFS were worse in low-risk patients than in non-mutated patients.Conclusion:RUNX1 gene mutation is an adverse prognostic factor in MDS patients,especially in the IPSS-M prognosis stratification group of low-risk,medium-low risk,medium-high risk and WHO classification of early patients.

Objective:The rehabilitation work for patients with motor dysfunction after stroke is crucial.However,there is currently a lack of summarized evidence regarding the rehabilitation management of stroke patients in rehabilitation wards,communities,and at home.This study aims to compile relevant evidence on the rehabilitation management of patients with motor dysfunction after stroke,providing a reference for clinical and community health professionals to carry out rehabilitation interventions. Methods:A systematic search was conducted in BMJ Best Practice,UpToDate,National Guidebook Clearinghouse,American Heart Association/American Stroke Association,Canadian Medical Association,National Institute for Health and Clinical Excellence,United States Department of Veterans Affairs/Department of Defense,Registered Nurses Association of Ontario,JBI Evidence-Based Healthcare Center Database,The Cochrane Library,PubMed,Web of Science,Embase,CINAHL,CNKI,Wanfang Database,SinoMed,and other databases for all literature on the rehabilitation management of patients with motor dysfunction after stroke.This included clinical decision-making,guidelines,expert consensuses,recommended practices,systematic reviews,and evidence summaries,with the search period spanning from the establishment of each database to October 2023.Two researchers independently evaluated the quality of the literature. Results:A total of twenty-one documents were included,consisting of 11 guidelines,2 expert consensus,and 8 systematic reviews.Evidence was extracted and integrated from the included literature,summarizing forty-five pieces of evidence across nine areas:rehabilitation management model,rehabilitation institutions,rehabilitation teams,timing of rehabilitation interventions,rehabilitation assessment,rehabilitation programs,rehabilitation duration and frequency,rehabilitation intensity,and rehabilitation support These covered comprehensive rehabilitation management content for stroke patients in the early,subacute,and chronic phases. Conclusion:The best evidence summarized in this study for the rehabilitation management of patients with motor dysfunction after stroke is comprehensive and of high quality.It provides important guidance for clinical and community healthcare professionals in carrying out rehabilitation interventions.When applying the evidence,it is recommended to consider the current condition of the stroke patient,the extent of motor dysfunction,environmental factors,and the patient's preferences.Then,select the most appropriate rehabilitation plan,and adjust the type and intensity of training according to each patient's specific needs and preferences.