The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
Testosterone/metabolism* ; Humans ; Male ; Circadian Clocks/genetics* ; Circadian Rhythm Signaling Peptides and Proteins/metabolism* ; Circadian Rhythm/physiology* ; Hypogonadism/metabolism* ; Erectile Dysfunction/metabolism* ; Infertility, Male/metabolism* ; Prostatic Neoplasms/metabolism* ; Men's Health

OBJECTIVES: To investigate the molecular epidemiology of children with phenylketonuria (PKU) in Gansu, China, providing foundational data for intervention strategies. METHODS: A retrospective analysis was conducted on 1 159 PKU families who attended Gansu Provincial Maternity and Child Care Hospital from January 2012 to December 2024. Sanger sequencing, multiplex ligation-dependent probe amplification, whole exome sequencing, and deep intronic variant analysis were used to analyze the PAH gene. RESULTS: For the 1 159 children with PKU, 2 295 variants were identified in 2 318 alleles, resulting in a detection rate of 99.01%. The detection rates were 100% (914/914) in 457 classic PKU families, 99.45% (907/912) in 456 mild PKU families, and 96.34% (474/492) in 246 mild hyperphenylalaninemia families. The 2 295 variants detected comprised 208 distinct mutation types, among which c.728G>A (14.95%, 343/2 295) had the highest frequency, followed by c.611A>G (4.88%, 112/2 295) and c.721C>T (4.79%, 110/2 295). The cumulative frequency of the top 23 hotspot variants reached 70.28% (1 613/2 295), and most variant alleles were detected in exon 7 (29.19%, 670/2 295). CONCLUSIONS Deep intronic variant analysis of the PAH gene can improve the genetic diagnostic rate of PKU. The development of targeted detection kits for PAH hotspot variants may enable precision screening programs and enhance preventive strategies for PKU.
Humans ; Phenylketonurias/epidemiology* ; Female ; Male ; Retrospective Studies ; Phenylalanine Hydroxylase/genetics* ; Mutation ; Child, Preschool ; China/epidemiology* ; Child ; Infant

This paper explores the impacts of accelerated rehabilitation protocols following anterior cruciate ligament reconstruction(ACLR)on bone tunnel enlargement(BTE).While accelerated rehabilitation can shorten the recovery time and improve the knee function,it may increase the risk of BTE.In the early rehabilitation phase after ACLR,excessive early weight-bearing and rapid progression of knee flexion angles should be avoided,along with the proper use of braces.Continuous passive motion is not recommended in the early phase post-ACLR to prevent potential effects on BTE.Further research is needed to investigate the mechanisms of BTE and develop more effective rehabilitation strategies.This will help to select appropriate rehabilitation protocols for patients and balance functional recovery with the risk of BTE,thereby reducing the revision rate and improving postoperative outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/rehabilitation*

Objective To investigate the relationship between insomnia,gastrointestinal symptoms,and glycosylated hemoglobin(HbA1c)levels in individuals diagnosed with type 2 diabetes mellitus(T2DM),as well as the related influencing factors.Methods A total of 910 T2DM patients treated in our multicenter from January 2022 to December 2022 were enrolled in this study.General information(gender,age,smoking and drinking history,exercise,course of disease,treatment and complications),HbA1c,Athens Insomnia Scale(AIS)scores and Gastrointestinal Symptoms Rating Scale(GSRS)scores of patients were collected.The differences of sleep and gastrointestinal symptoms between groups were analyzed,and the correlation between the differences and HbA1c was analyzed.Furthermore,the risk factors for non-standard HbA1c were analyzed.Results The AIS score and GSRS score in the HbA1c control group were less than those in the non-standard group(P＜0.01).Insomnia was reported by 37.0％of T2DM patients,and the HbA1c level in the insomnia group was significantly higher than that in the non-insomnia group(10.00％±2.38％vs.8.26％±1.73％,P＜0.01).Gastrointestinal symptoms were present in 57.5％of T2DM patients,and the HbA1c levels in the group with gastrointestinal symptoms were significantly higher than those in the group without gastrointestinal symptoms(9.26％±2.23％vs.8.43％±1.98％,P＜0.01).Furthermore,26.3％of T2DM patients experienced both insomnia and gastrointestinal symptoms.Remarkably,the HbA1c levels in the group with both insomnia and gastrointestinal symptoms were significantly higher than those in the group without either condition(10.18％±2.44％vs.8.45％±1.86％,P＜0.01).Correlation analysis demonstrated a significant association between sleep quality,gastrointestinal function,and HbA1c levels(P＜0.01).The logistic regression analysis result revealed that age,GSRS score,AIS score,and the presence of insomnia combined with gastrointestinal symptoms were independent risk factors for predicting HbA1c≥6.5％(P＜0.01).Having both insomnia and gastrointestinal symptoms concurrently was the strongest risk factor for substandard HbA1c control,and the risk of blood sugar control may increase about 5 times when both appear together.Conclusion Insomnia and gastrointestinal symptoms are common comorbidities in T2DM patients,showing a cross-interfering relationship,and they appear together with poor blood sugar control,interact causally,and amplify each other.

Objective To investigate the disease spectrum and pathogenic genes of inherited metabolic disorder(IMD)among neonates in Gansu Province of China.Methods A retrospective analysis was conducted on the tandem mass spectrometry data of 286 682 neonates who received IMD screening in Gansu Provincial Maternal and Child Health Hospital from January 2018 to December 2021.A genetic analysis was conducted on the neonates with positive results in tandem mass spectrometry during primary screening and reexamination.Results A total of 23 types of IMD caused by 28 pathogenic genes were found in the 286 682 neonates,and the overall prevalence rate of IMD was 0.63‰(1/1 593),among which phenylketonuria showed the highest prevalence rate of 0.32‰(1/3 083),followed by methylmalonic acidemia(0.11‰,1/8 959)and tetrahydrobiopterin deficiency(0.06‰,1/15 927).In this study,166 variants were identified in the 28 pathogenic genes,with 13 novel variants found in 9 genes.According to American College of Medical Genetics and Genomics guidelines,5 novel variants were classified as pathogenic variants,7 were classified as likely pathogenic variants,and 1 was classified as the variant of uncertain significance.Conclusions This study enriches the database of pathogenic gene variants for IMD and provides basic data for establishing an accurate screening and diagnosis system for IMD in this region.

Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

This article comprehensively reviews the research progress in the management principles of acute closed soft tissue injuries,summarizing the retention and updates of the four main principles (RICE,PRICE,POLICE,and PEACE&LOVE) at different stages.Traditional methods such as compression,elevation,rest,and protection remain valuable.However,with the advancement in rehabilitation philosophy,early active rehabilitation plays an increasingly important role in the tissue healing process.Traditional cold therapy remains a choice because of its benefits.Non-steroidal anti-inflammatory drugs play a positive role in relieving the acute pain and swelling and improving the function of soft tissue,being preferred by both patients and medical practitioners.Therefore,advantages outweigh disadvantages in the clinical application of non-steroidal anti-inflammatory drugs.Finally,modern medical models have begun to incorporate more social and psychological factors,focusing on patients' mental state and social environment,while guiding patients to actively participate in the rehabilitation process,which can accelerate the recovery process and improve treatment outcomes.
Humans ; Soft Tissue Injuries/therapy* ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use*

Alzheimer's disease (AD) is associated with the impairment of white matter (WM) tracts. The current study aimed to verify the utility of WM as the neuroimaging marker of AD with multisite diffusion tensor imaging datasets [321 patients with AD, 265 patients with mild cognitive impairment (MCI), 279 normal controls (NC)], a unified pipeline, and independent site cross-validation. Automated fiber quantification was used to extract diffusion profiles along tracts. Random-effects meta-analyses showed a reproducible degeneration pattern in which fractional anisotropy significantly decreased in the AD and MCI groups compared with NC. Machine learning models using tract-based features showed good generalizability among independent site cross-validation. The diffusion metrics of the altered regions and the AD probability predicted by the models were highly correlated with cognitive ability in the AD and MCI groups. We highlighted the reproducibility and generalizability of the degeneration pattern of WM tracts in AD.
Humans ; White Matter/diagnostic imaging* ; Diffusion Tensor Imaging/methods* ; Alzheimer Disease/complications* ; Reproducibility of Results ; Cognition ; Cognitive Dysfunction/complications* ; Brain/diagnostic imaging*

Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) μmol/L vs. (17.39±7.68) μmol/L; (95.82±34.88) μmol/L vs. (77.32±43.81) μmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.
Humans ; Male ; Adult ; Middle Aged ; Female ; Heart Failure/complications* ; Follow-Up Studies ; Retrospective Studies ; Heart-Assist Devices ; Quality of Life

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*