ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

Objective To construct a diagnostic and prognostic model for malignant pleural effusion (MPE) in patients with non-M1b stage (AJCC 7th edition) non-small cell lung cancer (NSCLC) by machine learning. Methods Retrospective analysis was conducted on patients diagnosed with NSCLC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015, excluding those in the M1b stage. Two sets of data were collected: data 1 (patients with non-M1b stage NSCLC, n=47 392) was used to construct the MPE diagnostic model; and data 2 (patients with M1a stage NSCLC and MPE, n=2 422) was used to construct a prognostic model. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to screen feature variables, with a training set and validation set ratio of 7:3. Models were built using eight machine learning algorithms, with evaluation metrics including accuracy, precision, recall, F1 score, area under the ROC curve (AUC), decision curve, calibration curve, and precision recall curve (PR), with ROC-AUC as the main evaluation metric. Results The incidence of MPE in patients with non-M1b stage NSCLC was 5.12%, and the 1-year survival rate of patients with MPE was 32.5%. LASSO regression identified nine diagnostic-related variables and 12 prognostic-related variables. The AUC values of the models constructed by eight machine learning algorithms all exceeded 0.70. The random forest model performed the best in the diagnostic model (training set AUC=0.908, validation set AUC=0.897), and the XGBoost model showed the best performance in the prognostic model (training set AUC=0.905, validation set AUC=0.875). Other evaluation indicators showed good results and balanced distribution. SHAP feature importance analysis showed that tumor size, lymph node metastasis, and histological type were important influencing factors for the occurrence of MPE, and chemotherapy intervention was the most remarkably prognostic factor. Conclusion The random forest diagnostic model constructed in this study can effectively predict the risk of MPE in patients with non-M1b stage NSCLC, and the XGBoost prognostic model can predict the prognosis of M1a-stage NSCLC patients with concurrent MPE.

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

In recent years， the number of special clinical cases related to assisted reproductive technology （ART） for pregnancy has been on the rise annually. For example， gamete donation， assisted reproduction for couples of advanced maternal ages， and the ownership and disposition of embryos when one or both partners pass away， all involve the health of offspring and conflicts of interest in the implementation of ART. Although China’s ethical principles for ART include the protection of the offspring， the detailed rules are vague and urgently need to be supplemented and improved. In addition， the clinical application of ART lacks legislative collaborative governance. The corresponding administrative departments， practitioners， and infertile couples should work together. Starting from the perspective of focusing on the well-being of offspring born from the clinical application of ART， while conducting clinical research to address technical challenges， efforts should be made to overcome ethical dilemmas in the application of technology， comprehensively consider the well-being of offspring born from assisted reproductive treatments and help them seek the best care to promote their healthy growth.

Objective: To investigate the prevalence and influencing factors of menopausal syndrome among postmenopausal women in Pan'an County, Zhejiang Province, so as to provide the basis for guiding the health management of postmenopausal women. Methods: From May 2023 to April 2024, the postmenopausal women aged 40 to 69 years in Pan'an County were selected using the random cluster sampling method. Demographic information, lifestyle and prevalence of gynecological diseases were collected through questionnaire surveys. The prevalence of menopausal syndrome was assessed by modified Kupperman Score Scale. Factors affecting menopausal syndrome were analyzed by a multivariable logistic regression model. Results: A total of 816 postmenopausal women were surveyed, with an mean age of (57.63±2.92) years and a mean natural menopause age of (49.85±2.13) years. There were 574 cases with menopausal syndrome, with a prevalence of 70.34%. Flashes and sweating, insomnia and irritability were common symptoms, accounting for 62.87%, 47.43% and 41.18%, respectively. Multivariable logistic regression analysis showed that monthly personal income of ≤5 000 yuan (<3 000 yuan, OR=3.124, 95%CI: 1.829-5.335; 3 000-5 000 yuan, OR=2.399, 95%CI: 1.370-4.201) and having gynecological diseases (OR=1.970, 95%CI: 1.292-3.004) were associated with a higher risk of menopausal syndrome, while average (OR=0.141, 95%CI: 0.072-0.276) or sufficient sleep quality (OR=0.095, 95%CI: 0.049-0.185) were associated with a lower risk of menopausal syndrome. Conclusion The prevalence of menopausal syndrome among postmenopausal women in Pan'an County is relatively high, and is mainly influenced by personal economic status, sleep quality and the presence of gynecological diseases.

Objective To explore the application effect of multimodal somatosensory exercise based on artificial intelligence technology in home rehabilitation exercise for elderly patients with chronic obstructive pulmonary dis-ease(COPD),so as to promote COPD patients to participate in home rehabilitation exercise.Methods Using the convenient sampling method,80 elderly patients with COPD admitted to the Department of Respiratory Medicine of a tertiary A hospital in Urumqi from November 2023 to February 2024 were selected as the research subjects.Ac-cording to the random number table method,they were divided into a control group and an experimental group,with 40 cases in each group.The control group adopted the traditional exercise training method,and the experimental group adopted the multi-modal somatosensory movement based on artificial intelligence technology for exercise in-tervention,with 5 times a week,and the intervention was implemented for 12 weeks.The pulmonary function index,modified Medical Research Council scale score,physical fitness level,Chronic Obstructive Pulmonary Disease As-sessment Test scale score and exercise compliance of the 2 groups were compared before intervention and 12 weeks after intervention.Results 77 patients completed the study,with 39 in the experimental group and 38 in the control group.The forced vital capacity,forced expiratory volume in one second,forced expiratory volume in one second to forced vital capacity ratio,physical fitness level and exercise compliance of the experimental group were higher than those of the control group,while the modified British Medical Research Council scale score and Chron-ic Obstructive Pulmonary Disease Assessment Test score were lower than those of the control group.The differences were statistically significant(P＜0.05).Conclusion Somatosensory exercise based on artificial intelligence technology can improve the lung function of the patients with COPD,improve the exercise compliance and physical fitness in-dicators of elderly patients and improve the quality of life of the patients.

Objective:To observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type Ⅰ and Ⅱ patients. Methods:A family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks.Results:Among the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type Ⅰ (proband of families 1 and 2) and 2 cases of type Ⅱ (proband of families 3 and 4). The diopters ranged from -8.00 to-18.00 D. BCVA ranged from no light perception to 0.6 -. There were 2 cases each of vitreous membrane-like and "bead-like" opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains Conclusion:The COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type Ⅰ in families 1 and 2, and type Ⅱ in families 3 and 4.