Background Frailty serves as a significant precursor to falls, disability, and mortality. Epidemiological evidence examining the impact of working hours on frailty remains scarce. Objective To explore the prevalence of frailty and the relationship between frailty and working hours among full-time middle-aged and older workers in China. Methods Data were derived from the 2020 China Health and Retirement Longitudinal Study (CHARLS). The study included full-time workers aged 45 years and above with a weekly working duration exceeding 35 h. Frailty was assessed using the Frailty Index (FI). First, the dose-response relationship between working hours and FI was explored using a generalized additive model (GAM). Second, univariate analyses were performed using t-tests, χ² tests, and the Jonckheere–Terpstra trend test. Restricted cubic splines (RCS) were introduced for modeling. Based on ordinal logistic regression models, covariates were adjusted sequentially to examine whether differences in frailty prevalence existed across different weekly working hour categories. Finally, subgroup analyses were performed. Results Among the 5504 included participants, the mean age was (56.41±7.30) years, with 2304 being female (41.86%). A total of 807 participants (14.66%) were identified as frail, and 2 686 participants (48.80%) were pre-frail. After standardization for gender and age according to the seventh national census data, the standardized prevalence of frailty and prefrailty were 18.89% and 47.25%, respectively. Significant higher proportions of frail individuals were found among those in non-managerial (73.73%), agricultural (64.06%), and non-employed (65.68%) occupations. Long working hours were prevalent: 2596 (47.17%) workers worked 41–60 h per week, 1649 (29.96%) worked >60 h per week, and only 1259 (22.87%) worked 35–40 h per week. GAM analysis showed a non-linear relationship between weekly working hours and FI. Restricted cubic spline analysis showed a statistically significant association between weekly working hours and frailty status (P=0.022). Logistic regression analysis revealed that individuals working more than 60 h per week had a 23% higher odds of frailty compared to those working 41–60 h (OR=1.23, 95%CI: 1.09, 1.38, P<0.01), while those working 35–40 h per week showed a 15% higher odds of frailty (OR=1.15, 95%CI: 1.01, 1.31, P=0.034). The subgroup analysis revealed that the positive association between working more than 60 h per week and frailty remained generally consistent across sex, age, urban/rural residence, occupational attributes, industry, or employment type, although the association did not reach statistical significance among non-rural residents and individuals aged 60 years and older. Conclusion The prevalence of frailty among full-time middle-aged and older labor force in China is relatively high, and the odds of frailty increases significantly among those who work more than 60 h per week. It is recommended to implement frailty prevention and management strategies targeting long-working-hour workers and to prioritize the impact of working duration on frailty.

ObjectiveTo evaluate the effects and safety of the optimized new Shengmai Powder （优化新生脉散方） on exercise tolerance in patients with chronic heart failure （CHF） of qi deficiency， blood stasis， and fluid retention syndrome. MethodsA randomized， double-blind， placebo-controlled trial was conducted. A total of 78 CHF patients with qi deficiency， blood stasis， and fluid retention syndrome were recruited and randomly assigned to a treatment group （39 cases） and a control group （39 cases）. On the basis of conventional western medical therapy， patients in the treatment group additionally received the optimized new Shengmai Powder granules， while the control group was given an oral placebo of optimized new Shengmai Powder granules. Patients in both groups took 30.6 g each time， twice a day， mixed with water for administration， with a total treatment course of 4 weeks. The primary outcomes were 6-minute walk distance （6MWD） and peak oxygen uptake （Peak VO₂） measured by cardiopulmonary exercise testing. Secondary outcomes included New York Heart Association （NYHA） functional classification， B-type natriuretic peptide （BNP） levels， cardiac function indexes including left ventricular ejection fraction （LVEF）， left ventri-cular end-systolic diameter （LVESD） and left ventricular end-diastolic diameter （LVEDD）， Minnesota Living with Heart Failure Questionnaire （MLHFQ） scores， and scores of four diagnostic information of traditional Chinese medicine （TCM）. All indicators were assessed once before and after treatment respectively. Safety indicators were evaluated， and adverse events during the trial were recorded. ResultsAll patients in both groups were included in the full ana-lysis set （FAS） and safety set （SS）. Compared with baseline， the 6MWD and Peak VO₂ of cardiopulmonary exercise test in the treatment group significantly increased after treatment， while the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information significantly decreased， and the NYHA cardiac function grade significantly improved （P＜0.01）. After treatment， the 6MWD and Peak VO₂ of cardiopulmonary exercise test， as well as their changes from baseline in the treatment group were higher than those in the control group； the MLHFQ scores， serum BNP levels and scores of TCM four diagnostic information in the treatment group were lower than those in the control group； and the improvement of NYHA cardiac function grade in the treatment group was superior to that in the control group （P＜0.01）. There was no statistically significant differences in all indicators after treatment in the control group （P＞0.05）. The incidence of adverse events was 5.1% （2/39） in the treatment group and 2.6% （1/39） in the control group， with no statistically significant difference between groups （P＞0.05）. ConclusionOn the basis of conventional western medicine treatment， the addition of the optimized new Shengmai Powder can further improve exercise tolerance， cardiac function and quality of life in patients with CHF of qi deficiency， blood stasis and fluid retention syndrome， and show good safety.

Chronic pancreatitis is a chronic inflammatory disease characterized by progre-ssive fibrosis of pancreatic tissue. Its pathological features primarily include parenchymal fibrosis, intraductal stone formation or calcification deposits, as well as segmental stenosis and dilation of the pancreatic duct. Prolonged chronic inflammatory stimulation not only leads to progressive pancreatic dysfunction but may also trigger the formation of pancreatic pseudocysts and even malignant transformation. In the comprehensive treatment of chronic pancreatitis, the core clinical goals are the removal of pancreatic duct stones, restoration of unobstructed pancreatic duct drainage, and preservation of residual pancreatic function. Traditional treatment strategies have been based on the principle of progressive intervention and early surgical management. In recent years, with advancements in extracorporeal shock wave lithotripsy, the application of new techniques such as endoscopic retrograde cholangiopancreatography combined with laser lithotripsy under direct cholan-gioscopic visualization, and improvements in pancreas-preserving surgical approaches, the debate over the superiority of progressive intervention versus early surgical treatment has intensified. Against this backdrop, the treatment mode of Xi′an Jiaotong University Pancreatic Disease Center (hereinafter referred to as "Western Pancreas") has emerged, emphasizing a personalized, multimodal treatment strategy based on different types of pancreatic duct stones. The treatment mode of "Western Pancreas" integrates lithotripsy, endoscopic treatment, and surgical interventions to optimize patient outcomes. By conducting a comprehensive analysis of domestic and international pancreatic duct stone classi-fication systems and drawing from our team′s clinical experience in managing over a thousand cases of chronic pancreatitis, the authors have further refined and proposed a classification system for pancreatic duct stones under the treatment mode of "Western Pancreas". This refinement aims to enhance the overall diagnostic and therapeutic standards for chronic pancreatitis.

Objective:To investigate the clinical value of laparoscopic evaluation of anato-mical position of inferior mesenteric artery (IMA), inferior mesenteric vein (IMV) and left colic artery (LCA).Methods:The prospective one-arm study was conducted. The clinical data of 229 pati-ents who underwent laparoscopic left hemicolectomy for left colon or laparoscopic radical resection of rectal cancer in The Second Affiliated Hospital of Air Force Medical University from December 2022 to December 2023 were selected. The distance between the origin point of IMA and the origin point of the first branch (L1) as well as the distance from the origin point of LCA root to the junction of LCA and IMV (L2) were measured during the operation. IMA classification, the location relation-ship of LCA and IMV junction were recorded. Observation indicators: (1) situations of enrolled patients; (2) difference analysis between L1, L2 and clinical features; (3) distribution characteristics of the location relationship between LCA and IMV in different types of IMA. Mann-Whitney U test was used for comparison of measurement data with skewed distribution between groups, Kruskal-Wallis H test was used for comparison between multiple groups, and Dunn-Bonferroni test was used for pairwise comparison. Comparison of count data between groups was performed by chi-square test. Pearson or Spearman correlation analysis was conducted for correlation of continuous variables. Results:(1) Situations of enrolled patients. A total of 229 eligible patients were screened out, including 146 males and 83 females, aged 64(range, 55-71)years. The height of 229 patients was 168(range, 160-172)cm, the weight was 65.0(55.5,71.5)kg, the body surface area was (1.68±0.17)m 2, the tumor maximum diameter was 3.0(2.5,4.0)cm. The total number of lymph nodes dissected was 19(17,21), and the number of No.253 lymph node dissected was 4(3,5). The L1 was 3.50(1.20,8.00)cm, and the L2 was 2.20(0.50,7.30)cm. There were 58, 31, 32, 71, 22, 90, 26 and 212 patients with smoking, alcohol drinking, diabetes, hypertension, coronary heart disease, neoadjuvant chemo-therapy, neoadjuvant radiotherapy and preservation of the LCA, respectively. Among 229 patients, cases with BMI <18.5 kg/m 2, 18.5-23.9 kg/m 2 and >23.9 kg/m 2 were 11, 133 and 85, respectively. There were 153 cases in pathological stage Ⅰ-Ⅱ and 76 cases in stage Ⅲ. There were 168 cases of Dixon operation, 6 cases of Miles operation and 55 cases of sigmoid colon resection. There were 135 cases of IMA type 1, 44 cases of IMA type 2, 23 cases of IMA type 3, 2 cases of IMA type 4, and 25 cases of IMA type unable to judge. (2) Difference analysis between L1, L2 and clinical features.Correlation analysis showed negative correlation between the height, body surface area and L1 ( r=-0.17, -0.15, P<0.05). The L1 was 3.20(2.68,4.00)cm for male patients and 3.60(3.00,4.20)cm for female patients, respectively, showing a significant difference between the two groups ( Z=-2.37, P<0.05). The L1 of patients with IMA type 1, 2, and 3 was 3.20(2.80,4.00)cm, 3.85(3.00,4.48)cm, and 3.20(2.50,4.30)cm, respectively, showing a significant difference among them ( H=7.54, P<0.05). Further pairwise com-parison showed that there was a significant difference in L1 between patients with IMA type 2 and those with IMA type 1 ( P<0.05). The L2 of smokers and non-smokers were 2.50(1.95,3.20)cm and 2.20(1.60,2.80)cm, respectively, showing a significant difference between the two groups ( Z=-2.24, P<0.05). (3)Distribution characteristics of the location relationship between LCA and IMV in different types of IMA. There was no significant difference in LCA distribution between the anterior and posterior positions of IMV among the three IMA types (type 1, 2, 3) ( χ2=1.63, P>0.05). Conclusions:Patients with greater height have larger body surface area and shorter L1. L1 is significantly longer in female patients than in male patients. L1 is significantly longer in patients with IMA type 2 than in those with type 1. L2 is significantly longer in smokers than in non-smokers. There was no significant difference in the distribution location between LCA and IMV among patients of IMA type 1, 2 and 3.

Given the lack of annotations for key lung organs and tissues in existing public datasets,this study collected 863 cases of chest CT scan images and constructed the first comprehensive dataset containing annotations of pulmonary vessels,airways,and nodules using a semi-automated method that combines computer vision algorithms with manual corrections by radiologists.On this basis,a lung nodule segmentation model based on multi-task learning is proposed.By incorporating annotations of pulmonary vessels(pulmonary arteries and veins)and the trachea to enhance model's ability to learn lung features,the proposed model reduces the false discovery rate in lung nodule detection,and improves generalization ability.Additionally,the use of larger image patches further optimizes model performance.The trained VAAN_128 model achieves the best performance,with a Dice coefficient of 0.694 and a false discovery rate of 0.210 for lung nodule segmentation.Moreover,it simultaneously provides accurate segmentation results of pulmonary vessels and the trachea,assisting in the formulation of more precise diagnosis and treatment plans.Based on the VAAN_128 model,a software system for navigation and localization in biopsy procedures is developed.In clinical practice,this system can assist physicians in accurately locating lung nodules,distinguishing critical tissues,and improving preoperative planning efficiency.This provides precise and efficient technical support for early diagnosis and disease monitoring of lung diseases,and is of great significance for path planning in clinical navigation system and future lung imaging research.

AKT,also known as Protein Kinase B(PKB),plays a critical role in cell proliferation and metabolism.There are three isoforms of AKT:AKT1,AKT2,and AKT3.The effects of these isoforms on the pluripotency and differentiation of mouse embryonic stem cells(mESCs)remain unclear.This study aims to explore the impact of three AKT isoform-specific knockouts on the self-renewal and differen-tiation of mouse embryonic stem cells.Using CRISPR/Cas9 gene-editing technology,AKT isoform-spe-cific knockout cell lines were established.The phenotypic and molecular changes were analyzed through Western blotting,flow cytometry,qRT-PCR,CCK-8 assays,Alkaline Phosphatase(AP)staining,and RNA-seq.The construction of AKT isoform-specific knockout cell lines was successful.The loss of AKT1 and AKT2 inhibited the proliferation of mESCs.The knockout of any single AKT isoform did not affect the expression of pluripotency genes at both mRNA or protein levels.However,during embryoid body forma-tion,the deletion of any of the three AKT isoforms affected the mRNA expression levels of genes in all three germ layers.Transcriptome analysis showed that compared to wild-type mESCs,995,547,and 429 differentially expressed genes(|log2FC|≧1,P＜0.05)were identified inAKT1,AKT2,and AKT3 isoform-specific knockout cells,respectively.There was some overlap in the differentially expressed genes regulated by these three isoforms.In conclusion,the independent knockout of AKT isoforms does not af-fect the maintenance of pluripotency in mouse embryonic stem cells,but they are crucial for differentia-tion.The three AKT isoforms can collectively regulate gene expression while retaining their own regulato-ry specificity.This study provides a foundation for understanding the unique and overlapping roles of AKT isoforms in stem cell biology,highlighting their importance in maintaining stem cell function and differen-tiation.

Objective:This article introduces a novel technique for totally laparoscopic, right thoracic approach, esophagojejunostomy for digestive tract reconstruction.Methods:A retrospective analysis was conducted on the clinical data of patients with adenocarcinoma of the esophagogastric junction who successfully underwent totally laparoscopic esophagojejunostomy via the right thoracic approach at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between February 2022 and March 2022.The surgical procedure was performed as follows:(1)Following total laparoscopic resection of the gastric tumor and lymph node dissection, the specimen was transected distal to the tumor margin. The specimen was then placed into a retrieval bag and extracted through the umbilical observation port.(2)Dissection was continued through the esophageal hiatus to mobilize the esophagus. The tumor-bearing tissue, along with the esophagus, was delivered into the thoracic cavity via the esophageal hiatus.(3)The jejunum was transected 20 cm distal to the ligament of Treitz. The distal Jejunum was mobilized for 15-20 cm and subsequently delivered into the thoracic cavity through the esophageal hiatus.(4)A Roux-en-Y jejunojejunostomy was constructed 45-50 cm distal to the cut end of the distal jejunal limb; the mesenteric defect was closed, and the duodenal stump was reinforced.(5)The patient was repositioned into the left lateral decubitus position. Port placement was established as follows: the observation port at the 7th intercostal space (ICS) in the right midaxillary line, the main operating port at the 4th ICS in the anterior axillary line, and the assistant operating port at the 9th ICS in the scapular line.(6)The main operating port incision was enlarged. Using a purse-string instrument, the esophagus was clamped and transected at least 5 cm proximal to the upper tumor margin, and the specimen was removed. (7)The distal jejunum was delivered into the thoracic cavity via the esophageal hiatus. Under total laparoscopic visualization, esophagojejunostomy was completed.Results:Both patients who underwent totally laparoscopic esophagojejunostomy via the right thoracic cavity successfully completed the procedure without conversion to laparotomy, unplanned reoperation, or any intraoperative/postoperative complications. The patients recovered well postoperatively, with no evidence of abdominal or thoracic hemorrhage. Postoperative computed tomography (CT) scans of the chest and abdomen confirmed the absence of anastomotic leakage or other related complications.Conclusions:The esophagojejunostomy was performed totally laparoscopically via the right thoracic cavity. This approach overcomes the drawback of significant trauma associated with open surgery while ensuring safe esophageal resection margins and thorough lymph node dissection. This technique offers advantages including minimal invasiveness, accelerated postoperative recovery, and a reduced incidence of reflux esophagitis. To our knowledge, no similar method of digestive tract reconstruction has been reported in the literature. Its novelty and clinical potential may offer new therapeutic options for patients with Siewert type II adenocarcinoma of the esophagogastric junction (AEG).

Objective:To investigate the safety and efficacy of the artery-first approach pancreaticoduo-denectomy (PD) combined with portal vein/superior mesenteric vein (PV/SMV) resection and reconstruction for pancreatic head malignancies.Methods:A retrospective analysis was conducted on 322 patients who underwent PD with PV/SMV resection and reconstruction at the Hepatobiliary Pancreatic Surgery Department of the First Hospital Affiliated to Naval Medical University between January 2016 and December 2022. Patients were divided into the artery-first approach PD group (AFA-PD group, n=165) and standard PD group (SPD group, n=157) based on surgical approach. Baseline characteristics, surgical outcomes, postoperative outcomes, pathological results and survival data were compared between two groups. Results:Compared to the SPD group, the AFA-PD group exhibited significantly reduced intraoperative blood loss (500 ml vs 600 ml), lower rates of obvious intraoperative blood loss (≥1 000 ml: 25.45% vs 40.13%), and decreased transfusion requirements (26.67% vs 52.87%). Postoperatively, the AFA-PD group demonstrated lower incidence of grade B/C pancreatic fistula (10.30% vs 19.75%) and higher textbook outcome achievement (78.79% vs 66.24%). Pathologically, the AFA-PD group achieved superior lymph node yield (20 nodes vs 18 nodes) and higher R 0 resection rates (79.39% vs 64.33%), particularly at the posterior pancreatic margin (96.97% vs 91.72%, P=0.040), SMA margin (92.07% vs 82.17%), and SMV margin (88.48% vs 78.98%). Multivariate logistic regression identified arterial invasion >180°, venous invasion >180°, lymph node metastasis, and the artery-first approach as independent predictors of R 0 resection. The AFA-PD group showed prolonged median survival (19.17 month vs 15.73 month). All aforementioned differences were statistically significant (all P value <0.05). Conclusions:The artery-first approach PD combined with PV/SMV resection and reconstruction is safe and effective for pancreatic head malignancies, significantly improving R 0 resection rates and patients' survival outcomes.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Given the lack of annotations for key lung organs and tissues in existing public datasets,this study collected 863 cases of chest CT scan images and constructed the first comprehensive dataset containing annotations of pulmonary vessels,airways,and nodules using a semi-automated method that combines computer vision algorithms with manual corrections by radiologists.On this basis,a lung nodule segmentation model based on multi-task learning is proposed.By incorporating annotations of pulmonary vessels(pulmonary arteries and veins)and the trachea to enhance model's ability to learn lung features,the proposed model reduces the false discovery rate in lung nodule detection,and improves generalization ability.Additionally,the use of larger image patches further optimizes model performance.The trained VAAN_128 model achieves the best performance,with a Dice coefficient of 0.694 and a false discovery rate of 0.210 for lung nodule segmentation.Moreover,it simultaneously provides accurate segmentation results of pulmonary vessels and the trachea,assisting in the formulation of more precise diagnosis and treatment plans.Based on the VAAN_128 model,a software system for navigation and localization in biopsy procedures is developed.In clinical practice,this system can assist physicians in accurately locating lung nodules,distinguishing critical tissues,and improving preoperative planning efficiency.This provides precise and efficient technical support for early diagnosis and disease monitoring of lung diseases,and is of great significance for path planning in clinical navigation system and future lung imaging research.