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.

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.

Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

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

OBJECTIVE: To explore the effect of light music therapy on delirium in intensive care unit (ICU) patients undergoing invasive mechanical ventilation, and provide evidence-based support for clinical prevention of delirium. METHODS: A prospective randomized controlled trial was conducted. 140 patients with invasive mechanical ventilation admitted to the department of respiratory and critical care medicine of First Affiliated Hospital of Guangxi Medical University from January 2024 to January 2025 were enrolled. The patients were divided into intervention group and control group using a random number table method. The control group received routine treatment and nursing care, while the intervention group received light music therapy three times a day for 30 minutes each time for 7 consecutive days. The confusion assessment method-ICU (CAM-ICU) was used to evaluate delirium, and the incidence of delirium within 7 days was statistically analyzed. Richmond agitation-sedation score (RASS), critical care pain observation tool (CPOT) score, mechanical ventilation duration, the length of ICU stay, and ICU stay expenses were record. RESULTS: 129 cases were ultimately included, including 64 cases in the control group and 65 cases in the intervention group. There was no statistically significant difference in baseline data between the two groups, indicating comparability. The incidence of delirium in the intervention group was significantly lower than that in the control group (27.7% vs. 51.6%, χ ² = 7.687, P = 0.006). There was no significantly difference in RASS score between the two groups before enrollment (P = 0.840). After intervention, the RASS score in the intervention group significantly decreased, from 2.00 points on the 1st day of enrollment to 0.00 points on the 7th day, while the control group only decreased from 2.00 points to 1.50 points. The decreasing trend of the intervention group was more pronounced, especially on the 3rd day (P = 0.047) and the 7th day (P =0.005), with significant differences between the groups. The time effect (F = 18.929, P < 0.001), group effect (F = 6.655, P = 0.011), and time group interaction effect (F = 7.372, P < 0.001) of the two groups of RASS score were significant, suggesting that light music therapy has better timeliness and sustainability in improving patients' sedation status. There was no significantly difference in CPOT score between the two groups before enrollment (P = 0.902). After intervention, the CPOT score in the intervention group rapidly decreased from 3.00 points before enrollment to 1.00 points on the 1st day, and continued until the 7th day, while the control group showed a slower decrease from 2.50 points to 2.00 points and only dropped to 1.00 points on the 7th day. There were significant differences on 1st day and 3rd day between two groups (both P < 0.05). The time effect (F = 28.125, P < 0.001), group effect (F = 11.580, P = 0.001), and time group interaction effect (F = 4.048, P = 0.020) of the two groups of CPOT score were significant, indicating that light music therapy has better pain control, but the interaction effect is low, indicating that the impact of the intervention on the CPOT score was mainly concentrated in the early stage (1-3 days), and the long-term effect may be influenced by other factors. Compared with the control group, the intervention group showed a significant reduction in mechanical ventilation time (days: 10.57±2.94 vs. 11.95±3.74, P = 0.021) and the length of ICU stay (days: 14.91±4.37 vs. 17.53±4.83, P = 0.002). The ICU hospitalization expenses of the intervention group was slightly lower than that of the control group [ten thousand yuan: 22.431 (12.473, 28.489) vs. 29.362 (11.996, 41.389)], but the difference was not statistically significant (P = 0.086). CONCLUSIONS Light music therapy can effectively reduce the incidence of delirium in patients undergoing invasive mechanical ventilation, improve consciousness and pain perception, shorten mechanical ventilation time and hospital stay, and has significant clinical promotion value high-quality studies.
Humans ; Delirium/prevention & control* ; Intensive Care Units ; Respiration, Artificial ; Music Therapy ; Prospective Studies ; Male ; Female ; Middle Aged ; Critical Care ; Aged

To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system, understand the distribution of evidence in this field, and provide reference for subsequent evidence research.

Objective:To retrospectively analyze the clinical phenotype and pathogenic variants in patients with Progressive myoclonus epilepsy (PME).Methods:Clinical data and results of genetic testing for 11 patients diagnosed with PME at the Department of Neurology, the First Affiliated Hospital of Zhejiang University School of Medicine from June 2017 to December 2022 were collected and analyzed.Results:All of the patients, including 4 males and 7 females, had predominant action myoclonus. Three patients had myoclonus as the initial manifestation, whilst eight were diagnosed through genetic testing, including three cases with NEU1 gene variants, two with EPM2A gene variants (1 was novel), one with MT- TK gene variant, one with ATN1 gene variant, and one with CSTB gene variant. No pathogenic variant was identified in the remaining three cases. Among the eight patients with a genetic diagnosis, three were diagnosed with sialidosis, two with Lafora disease, one with Dentatorubral-pallidoluysian atrophy (DRPLA), one with Unverricht-Lundborg disease (ULD), and one with Myoclonic epilepsy with ragging red fibers (MERRF). Conclusion:Compared with pediatric patients, adult patients with PME represent a distinct subtype with slower progression and milder cognitive impairment.

Objective To explore the mechanism of ginsenoside Rg1 in alleviating heat stress-induced testicular injury in mice.Methods A total of 20 C57BL/6 male mice(6～8 weeks old)were randomly divided into 4 groups(n=5).The mice from the control group and heat stress(HS)group were intraperitoneally injected with 10 mL/(kg·d)0.9％normal saline for 14 d,while those in the HS+Rg1 group and the Rg1 group were given an intraperitoneal injection of 20 mg/(kg·d)for 14 d,and then on the 7th day after administration,the mice in the HS group and the HS+Rg1 group had the lower abdomen put into a 43 ℃ water bath for 30 min as a single heat stress after being anesthetized with 4％chloral hydrate.Mouse spermatocytes GC-2spd(ts)were divided into control group(routine culture for 48 h),HS group(placed in a 43 ℃ water bath for 30 min after 36 h of conventional culture,and cultured till the end of 48 h),HS+Rg1 group(50 μmol/L Rg1 treatment followed by heat stress injury),and Rg1 group(no heat stress injury).In 1 d after modeling,the eyeball blood samples were collected to detect serum testosterone with ELISA,and the testicles were extracted to observe the morphology and weighed to calculate the testicular index.HE staining was used to observe the histopathology of testis,and corresponding reagents and kits was employed to detect the content of malondialdehyde(MDA)and activities of catalase(CAT)and superoxide dismutase(SOD)in testis tissue.After the epididymal sperm were collected,the sperm concentration and motility were analyzed by computer-assisted sperm analysis(CASA)system.In in vitro experiments,cell apoptosis was detected with TUNEL staining,the protein levels of Nrf2,Keap1,HO-1,Bax,Bcl-2 and Caspase3 were detected with Western blotting,and the mRNA levels of GCLC,GCLM and NQO1 were detected by RT-qPCR.Results Rg1 prevented the decreases in testicular weight and testicular index caused by heat stress,reduced the damage of testicular tissue structure,prevented the decrease of sperm concentration and vitality,antagonized the decreasd number of Leydig cells and serum testosterone level,reduced the accumulation of MDA in testicular tissue,and enhanced the activities of CAT and SOD.Rg1 treatment alleviated the apoptosis of GC-2spd(ts)cells,down-regulated the expression of Bax,Caspase3 and Keap1 proteins,enhanced the expression of Bcl-2,Nrf2 and HO-1 proteins,and increased the transcriptional levels of Nrf2 target genes GCLC,GCLM and NQO1.Conclusion Rg1 has no significant effect on the structure and function of mouse testes,but it can effectively improve the ability of mouse testes to resist heat stress injury,which may be related to the activation of Nrf2 signaling pathway,the improvement of antioxidant enzyme activity,and the reduction of apoptosis of spermatogenic cells.

Objective:To explore the feasibility of predicting complexity of intensity modulated radiotherapy(IMRT)plan through adopted machine learning method to extract planomics features of radiotherapy,so as to provide a new method for comprehensive evaluation of the complexity of IMRT plan.Methods:The medical case data of 3203 patients with pelvic tumor,or abdominal tumor or head and neck tumor,who admitted to The First Affiliated Hospital with Nanjing Medical University from December 2022 to November 2023,were selected.All patients adopted Monaco system to conduct design for plan,and underwent treatment on Precise and Axesse accelerators.The evaluation indicator of complexity of 10 plans was calculated by using Python software,and the planomics features in the files of radiotherapy plans were extracted through format conversion and pyradiomics tool of imaging omics.The planomics features of radiotherapy were selected through data cleaning,filtering method and embedding method of machine learning.The corresponding predictive model of the evaluation indicator of complexity of 10 common plans was respectively constructed through used Gradient Boosting Decision Tree algorithm.The goodness of fit(R2)was adopted to evaluate the prediction performance of the model,and the 5-fold cross-validation method was adopted to detect the generalization ability of the model.Results:There were statistically significant differences between Precise accelerator and Axesse accelerator in average leaf to area(LA),plan irregularity(PI)of beam shape and standard circle,modulation complexity score(MCS)of the variability between shape and area of subfield,and the advantage value of leaf travel(LT)(t=63.894,-63.678,72.582,-48.858,P＜0.01),respectively.A total of 107 planomics features were extracted through pyradiomics tool,and 38 features were remained after filtering method conducted screening,and 4 to 11 features were remained after embedding method conducted screening.The goodness of fits of mean field area(MFA),LA and leaf gap average(LGA)value were better in the validation set,with R2＞0.970,however the goodness of fits of the proportion of small aperture score 20 mm(SAS20)was poor in validation set,with R2=0.917.The 5-fold cross-validation results showed that the average value of prediction accuracy of all indicators of complexity was＞90％.Conclusions:The extracted planomics features of radiotherapy based on radiomics method can accurately predict the complexity of IMRT plan,which are expected to play a greater role in improving the ensure efficiency of individual quality of patient,and screening radiotherapy plan with higher-quality.