BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

Autism Spectrum Disorder （ASD） is a neurodevelopmental disorder with rapidly increasing global prevalence， characterized by core symptoms of social communication deficits and stereotyped repetitive behaviors. Although genetic predisposition， abnormal epigenetic regulation， perinatal environmental exposure， and nutritional-metabolic imbalances are recognized as major risk factors， the precise etiological mechanisms remain incompletely understood. Current clinical management primarily relies on behavioral interventions， with limited pharmacological options accompanied by adverse effects. Recent studies have demonstrated the unique therapeutic value of active components from Chinese herbal medicine in ASD intervention. This article reviews the mechanisms underlying various Chinese herbal active components in ASD treatment， including improvements in synaptic dysfunction， blood-brain barrier impairment， neurotransmitter regulation， cerebellar dysfunction， immune dysregulation and neuroinflammation， oxidative stress， programmed neuronal cell death， and lipid metabolism. These bioactive components exhibit multi-target and multi-pathway regulatory effects， providing novel therapeutic strategies and directions for ASD.

ObjectiveTo investigate whether Carthamus tinctorius L.-derived nanovesicles （CDNVs） can alleviate angiotensin Ⅱ （ANGⅡ）-induced cardiomyocyte （H9C2） hypertrophy by inhibiting the NF-κB signaling pathway and to elucidate the underlying molecular mechanisms. MethodsCDNVs were isolated and purified by ultracentrifugation combined with sucrose density gradient centrifugation， and their morphology and particle size distribution were identified by transmission electron microscopy and nanoparticle tracking analysis. Rat H9C2 cardiomyocytes were cultured in vitro and randomly divided into the normal control group （NC）， ANGⅡ （1.0 μmol/L） group， ANGⅡ+CDNVs group， and ANGⅡ+CDNVs+NF-κB activator 1 group. After 24 h of intervention， cell viability was detected by the CCK-8 assay， the expression of myocardial hypertrophy-related genes （ANP， BNP） was determined by qPCR， the relative cell area was measured by phalloidin staining， the expression of hypertrophy marker proteins and NF-κB pathway proteins （P-p65/p65， P-IκBα/IκBα） was examined by Western blot， and nuclear translocation of p65 was observed by immunofluorescence. Subsequently， NF-κB signaling pathway agonist activator 1 was added， and the expression of myocardial hypertrophy marker proteins and NF-κB pathway proteins was detected. ResultsCDNVs exhibited a typical round-like vesicle structure with an average particle size of 140.4 nm， which was consistent with the morphological characteristics of exosomes. ANGⅡ at concentrations of 0.1-1.0 μmol/L had no significant effect on cardiomyocyte viability. Compared with the NC group， ANGⅡ significantly upregulated the gene expression of ANP and BNP， increased the relative surface area of cardiomyocytes， elevated the levels of myocardial hypertrophy marker proteins and NF‑κB pathway proteins， and promoted the nuclear translocation of p65 （P<0.05）. Following treatment with CDNVs， all the above indicators were markedly reduced in comparison with the ANGⅡ group （all P<0.05）. However， all these experimental results were reversed after the addition of an NF‑κB agonist. ConclusionCDNVs alleviate ANGⅡ-induced H9C2 cell hypertrophy by inhibiting the NF-κB signaling pathway.

ObjectiveTo verify the protective effect and pharmacological mechanism of Qishen granules against doxorubicin-induced cardiotoxicity， thus providing a basis for developing new drug options for clinical treatment of cardio-oncology disease. MethodsFifty mice were randomly assigned into a normal group （n=10） and a modeling group （n=40）. The model was established by intravenous injection of doxorubicin （5 mg·kg^-1） via the tail vein， once a week for 4 consecutive weeks. The normal group was injected with an equal volume of normal saline during the same period. The modeled mice were further assigned into four groups： doxorubicin （no drug control）， low-dose （3.33 mg·kg^-1） Qishen granules， high-dose （6.67 mg·kg^-1） Qishen granules， and enalapril （15 mg·kg^-1）. Mice were administrated with corresponding drugs by gavage for 4 consecutive weeks. At the end of the experiment， echocardiography， histopathological staining， and live-cell imaging were employed to determine relevant indicators， on the basis of which the protective effect of Qishen granules against doxorubicin-induced cardiotoxicity was evaluated. ResultsCompared with the normal group， doxorubicin treatment reduced the left ventricular ejection fraction （LVEF） （P<0.05） and caused pathological changes including disarrangement of cardiomyocytes， increased cell spacing， cardiomyocyte hypertrophy， and increased apoptosis in the heart tissue. Meanwhile， doxorubicin prolonged the mitochondria-lysosome contact time， downregulated the expression of TBC1 domain family member 15 （TBC1D15） （P<0.01）， upregulated the levels of microtubule-associated protein 1 light chain 3 （LC3） and sequestosome 1 （p62） （P<0.01）， and induced mitochondrial cristae breakage， resulting in mitochondrial dysfunction. Compared with the doxorubicin group， intervention with Qishen granules reversed the above indicators. It not only increased the LVEF （P<0.01） and alleviated pathological damage to the heart， but also upregulated the expression of TBC1D15 （P<0.01）， shortened the mitochondria-lysosome contact time （P<0.05）， and downregulated the protein levels of LC3 and p62. When TBC1D15 in cells was knocked down， the autophagy-activating and mitochondrion-protecting effects of Qishen granules partially disappeared. ConclusionQishen granules upregulate the expression of TBC1D15 to shorten the mitochondria-lysosome contact time， thereby activating autophagy and ultimately exerting a protective effect against doxorubicin-induced cardiotoxicity.

ObjectiveTo investigate the protective effect of Astragaloside Ⅳ （AS-Ⅳ） on D-galactose （D-gal）-induced cardiomyocytes senescence and its potential mechanisms. MethodsUsing H9C2 cardiomyocytes as a model， D-gal was used to induce cardiomyocyte senescence. Cell viability was assessed using the CCK-8 assay， senescenceextent was evaluated via β-galactosidase （SA-β-Gal） staining， reactive oxygen species （ROS） levels were measured to assess intracellular oxidative stress， apoptosis extent was determined using the TUNEL assay， and qRT-PCR and Western blot analyses were conducted to examine the expression levels of senescence-related genes and proteins （p21、p53） and key genes （STING， CXCL10， and MX-1） and proteins （STING， cGAS， p-IRF3/IRF3） of the stimulator of interferon genes （STING） pathway. ResultsThe 50 g/L D-gal significantly reduced myocardial cell viability， increased SA-β-Gal positivity， apoptosis rate， and intracellular reactive oxygen species levels， and upregulated the expression of p16， p21， and STING， cGAS， p-IRF3/IRF3 pathway proteins （P< 0.05）； After intervention with 200 μmol/L of AS-Ⅳ， cell viability was significantly enhanced， the SA-β-Gal-positive rate decreased， intracellular reactive oxygen species levels decreased， oxidative stress damage was alleviated， myocardial cell apoptosis was inhibited， and the mRNA and protein levels of aging-related p21 and p53 were downregulated （P＜0.05）. Further detection of STING pathway-related molecules showed that 200 μmol/L of AS-IV inhibited D-galactose-induced STING mRNA and protein expression and reduced p-IRF3/IRF3 protein expression levels， as demonstrated by qRT-PCR and Western blot results. However， the SA-β-Gal positivity rate， intracellular reactive oxygen species （ROS） levels， DNA damage results， and Western blot findings suggested that the STING agonist （STING agonist-7） could reverse the ameliorative effects of AS-Ⅳ on D-galactose-induced cardiomyocytes senescence. ConclusionAS-Ⅳ may mitigate D-gal-induced cardiomyocytes senescence by inhibiting STING pathway activation， providinga new strategy for the prevention and treatment of cardiovascular senescence-related diseases.

ObjectiveTo verify the protective effect and pharmacological mechanism of Qishen granules against doxorubicin-induced cardiotoxicity， thus providing a basis for developing new drug options for clinical treatment of cardio-oncology disease. MethodsFifty mice were randomly assigned into a normal group （n=10） and a modeling group （n=40）. The model was established by intravenous injection of doxorubicin （5 mg·kg^-1） via the tail vein， once a week for 4 consecutive weeks. The normal group was injected with an equal volume of normal saline during the same period. The modeled mice were further assigned into four groups： doxorubicin （no drug control）， low-dose （3.33 mg·kg^-1） Qishen granules， high-dose （6.67 mg·kg^-1） Qishen granules， and enalapril （15 mg·kg^-1）. Mice were administrated with corresponding drugs by gavage for 4 consecutive weeks. At the end of the experiment， echocardiography， histopathological staining， and live-cell imaging were employed to determine relevant indicators， on the basis of which the protective effect of Qishen granules against doxorubicin-induced cardiotoxicity was evaluated. ResultsCompared with the normal group， doxorubicin treatment reduced the left ventricular ejection fraction （LVEF） （P<0.05） and caused pathological changes including disarrangement of cardiomyocytes， increased cell spacing， cardiomyocyte hypertrophy， and increased apoptosis in the heart tissue. Meanwhile， doxorubicin prolonged the mitochondria-lysosome contact time， downregulated the expression of TBC1 domain family member 15 （TBC1D15） （P<0.01）， upregulated the levels of microtubule-associated protein 1 light chain 3 （LC3） and sequestosome 1 （p62） （P<0.01）， and induced mitochondrial cristae breakage， resulting in mitochondrial dysfunction. Compared with the doxorubicin group， intervention with Qishen granules reversed the above indicators. It not only increased the LVEF （P<0.01） and alleviated pathological damage to the heart， but also upregulated the expression of TBC1D15 （P<0.01）， shortened the mitochondria-lysosome contact time （P<0.05）， and downregulated the protein levels of LC3 and p62. When TBC1D15 in cells was knocked down， the autophagy-activating and mitochondrion-protecting effects of Qishen granules partially disappeared. ConclusionQishen granules upregulate the expression of TBC1D15 to shorten the mitochondria-lysosome contact time， thereby activating autophagy and ultimately exerting a protective effect against doxorubicin-induced cardiotoxicity.

Epigenetics is the link between the genome and environment, which can respond to physiological (such as age) or environmental factors (such as diet, stress, and pollution) and induce changes in epigenetic modifications (such as DNA methylation, non-coding RNA, and histone modifications). It can also serve as cellular memory transmitted from generation to generation. Sperm is highly responsive to such environmental changes and has unique epigenetic profiles. The paternal inter-/trans-generational inheritance mediated by sperm epigenetic changes is closely related to the health of offspring, which is an issue of great concern. This review has summarized the epigenetic mechanisms of paternal inter-/trans-generational inheritance and recent studies on the paternal inheritance mediated by sperm epigenetic changes in human and mice, which may facilitate understanding of the relationship between paternal epigenetic changes and the health of offspring caused by physiological or environmental changes and provide a basis for genetic counseling and clinical intervention.
Epigenesis, Genetic ; Humans ; Male ; Animals ; Spermatozoa/metabolism* ; DNA Methylation ; Paternal Inheritance ; Mice

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.