ObjectiveTo explore the effect of serum containing Zhenwutang on myocardial mast cell apoptosis induced by angiotensin Ⅱ （AngⅡ） and the mechanism of the correlation between apoptosis and mitochondrial autophagy. MethodsIn this experiment， AngⅡ and serum containing Zhenwutang with different concentrations were used to interfere with H9C2 cardiomyocytes for 24 h， and the survival rate of H9C2 cardiomyocytes was detected by cell counting kit-8 （CCK-8） to screen the optimal concentration for the experiment. Enzyme-linked immunosorbent assay （ELISA） was used to detect the content of B-type natriuretic peptide （BNP） in cell culture supernatant， and immunofluorescence was used to detect the cell surface area to verify the construction of the myocardial mast cell model. Subsequently， the experiment was divided into a blank group （20% blank serum）， a model group （20% blank serum + 5×10^-5 mol·L^-1 AngⅡ）， low-， medium-， and high-dose （5%， 10% and 20%） serum containing Zhenwutang groups， an autophagy inhibitor group （1×10^-4 mol·L^-1 3-MA）， and autophagy inducer group （1×10^-7 mol·L^-1 rapamycin）. The apoptosis level of H9C2 cells and the changes of mitochondrial membrane potential were detected by flow cytometry. The lysosomal probe （Lyso Tracker） and mitochondrial probe （Mito Tracker） co-localization was employed to detect autophagy. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect Caspase-3， Caspase-9， B-cell lymphoma 2 （Bcl-2）， Bcl-2-related X protein （Bax）， and cytochrome C （Cyt C） in apoptosis-related pathways and the relative mRNA expression of ubiquitin ligase （Parkin）， phosphatase and tensin homolog （PTEN）-induced kinase 1 （PINK1）， and p62 protein in mitochondrial autophagy-related pathways. Western blot was used to detect cleaved Caspase-3， cleaved Caspase-9， Bax， Bcl-2， and Cyt C in apoptosis-related pathways， phosphorylated ubiquitin ligase （p-Parkin）， phosphorylated PTEN-induced kinase 1 （p-PINK1）， p62， and Bcl-2 homology domain protein Beclin1 in mitochondrial autophagy-related pathways， and the change of microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ ratio. ResultsCCK-8 showed that when the concentration of AngⅡ was 5×10^-5 mol·L^-1， the cell activity was the lowest， and there was no cytotoxicity. At this concentration， the surface area of cardiomyocytes was significantly increased （P<0.01）， and the content of BNP in the supernatant of culture medium was significantly increased （P<0.05）. Therefore， AngⅡ with a concentration of 5×10^-5 mol·L^-1 was selected for the subsequent modeling of myocardial mast cells. Compared with the blank group， the model group and the autophagy inhibitor 3-MA group had a significantly increased apoptosis rate （P<0.01） and significantly decreased mitochondrial membrane potential （P<0.01）. The results of immunofluorescence co-localization showed that compared with the blank group， the model group had a significantly decreased number of red and green fluorescence spots. The results of Real-time PCR showed that compared with that in the blank group， the relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 in the model group was significantly up-regulated （P<0.01）， while the relative mRNA expression of Bcl-2， Parkin， and PINK1 was significantly down-regulated （P<0.01）. In addition， the relative protein expression of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 was significantly up-regulated （P<0.01）. The LC3Ⅱ/Ⅰ was significantly decreased， and the relative protein expression of Bcl-2， p-Parkin， p-PINK1， and Beclin1 was significantly down-regulated （P<0.01）. Compared with the model group， the serum containing Zhenwutang groups and the autophagy inducer group had significantly decreased apoptosis rate （P<0.01）， and the decrease ratio of mitochondrial membrane potential is significantly lowered （P<0.01） in a dose-dependent manner. Additionally， both red and green fluorescence spots became more in these groups. In the 3-MA group， the number of red and green fluorescence spots decreased significantly. The relative mRNA expression of Bax， Caspase-3， Caspase-9， Cyt C， and p62 was significantly down-regulated （P<0.05， P<0.01）， while that of Bcl-2， Parkin， and PINK1 was significantly up-regulated （P<0.01）. In the serum containing Zhenwutang groups， the relative protein expression levels of Bax， cleaved Caspase-3， cleaved Caspase-9， Cyt C， and p62 were significantly down-regulated （P<0.05，P<0.01）. The LC3Ⅱ/Ⅰ was significantly increased， and the relative protein expression levels of Bcl-2， p-Parkin， p-PINK1， and Beclin1 were significantly up-regulated （P<0.01）. ConclusionThe serum containing Zhenwutang can reduce the apoptosis of myocardial mast cells and increase mitochondrial autophagy. This is related to the inhibition of intracellular Bax/Bcl-2/Caspase-3 apoptosis pathway and regulation of Parkin/PINK1 mitochondrial autophagy 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.

Surgical methods for varicocele remain controversial. This study intends to evaluate the efficacy and safety of different surgical approaches for treating varicocele through a network meta-analysis (NMA). PubMed, Embase, Cochrane, and Web of Science databases were thoroughly searched. In total, 13 randomized controlled trials (RCTs) and 24 cohort studies were included, covering 9 different surgical methods. Pairwise meta-analysis and NMA were performed by means of random-effects models, and interventions were ranked based on the surface under the cumulative ranking curve (SUCRA). According to the SUCRA, microsurgical subinguinal varicocelectomy (MSV; 91.6%), microsurgical retroperitoneal varicocelectomy (MRV; 78.2%), and microsurgical inguinal varicocelectomy (MIV; 76.7%) demonstrated the highest effectiveness in reducing postoperative recurrence rates. In this study, sclerotherapy embolization (SE; 87.2%), MSV (77.9%), and MIV (67.7%) showed the best results in lowering the risk of hydrocele occurrence. MIV (82.9%), MSV (75.9%), and coil embolization (CE; 58.7%) were notably effective in increasing sperm motility. Moreover, CE (76.7%), subinguinal approach varicocelectomy (SV; 69.2%), and SE (55.7%) were the most effective in increasing sperm count. SE (82.5%), transabdominal laparoscopic varicocelectomy (TLV; 76.5%), and MRV (52.7%) were superior in shortening the length of hospital stay. The incidence rates of adverse events for MRV (0), SE (3.3%), and MIV (4.1%) were notably low. Cluster analyses indicated that MSV was the most effective in the treatment of varicocele. Based on the existing evidence, MSV may represent the optimal choice for varicocele surgery. However, selecting clinical surgical strategies requires consideration of various factors, including patient needs, surgeon experience, and the learning curve.
Humans ; Male ; Embolization, Therapeutic/methods* ; Microsurgery/methods* ; Randomized Controlled Trials as Topic ; Sclerotherapy/methods* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; Varicocele/surgery*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective:To evaluate the effect of s-ketamine on perioperative myocardial injury in patients undergoing liver transplantation.Methods:This was a prospective randomized controlled study. Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ patients, aged 18-64 yr, with New York Heart Association classⅠ-Ⅲ, undergoing elective liver transplantation with general anesthesia in our hospital from May to October 2023, were divided into 2 groups ( n=30 each) using a random number table method: s-ketamine group (group S) and control group (group C). In group S, s-ketamine was intravenously injected at a dose of 0.5 mg/kg after induction of anesthesia, followed by an infusion of 0.5 mg·kg -1·h -1 until the end of surgery. The equal volume of normal saline was given instead in group C. Central venous blood samples were collected after induction of anesthesia (T 0), at 30 min of anhepatic phase (T 1), 30 min of neopepatic phase (T 2), abdominal closure (T 3), 24 h after operation (T 4) and 72 h after operation (T 5) for determination of the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α, interleukin-6 (IL-6), IL-10 and high-mobility group protein B1 by enzyme-linked immunosorbent assay. The occurrence of adverse cardiac events during surgery and within 24 h after surgery, postoperative mechanical ventilation time, time of intensive care unit stay, and postoperative length of hospital stay were recorded. Results:Compared with group C, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α and IL-6 at T 2-5 and high-mobility group protein B1 at T 2-4 were significantly decreased, the concentrations of serum IL-10 were increased at T 2-5, the incidence of myocardial ischemia was decreased, the mechanical ventilation time was shortened ( P<0.05), and no significant change was found in the time of intensive care unit stay and postoperative length of hospital stay in S group ( P>0.05). Conclusions:Intraoperative usage of s-ketamine can inhibit the inflammatory responses and reduce perioperative myocardial injury in the patients undergoing liver transplantation.

Aim To investigate the effect of ellagic acid (EA) on cognitive function in APP/PS 1 double- transgenic mice, and to explore the regulatory mechanism of ellagic acid on the level of oxidative stress in the hippocampus of double-transgenic mice based on the phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3 (PI3K/AKT/GSK-3 β) signaling pathway. Methods Thirty-two SPF-grade 6-month-old APP/PS 1 double transgenic mice were randomly divided into four groups, namely, APP/PS 1 group, APP/PS1 + EA group, APP/PS1 + LY294002 group, APP/PS 1 + EA + LY294002 group, with eight mice in each group, and eight SPF-grade C57BL/6J wild type mice ( Wild type) were selected as the blank control group. The APP/PS 1 + EA group was given 50 mg · kg

Objective:To investigate the application value of biological muscle flap in laparo-scopic radical proximal gastrectomy with esophagogastric anastomosis.Methods:The retrospec-tive and descriptive study was conducted. The clinicopathological data of 10 patients with adeno-carcinoma of esophagogastric junction who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from May 2023 to August 2023 were collected. All patients were males, aged (65±5)years. All patients underwent laparoscopic radical proximal gastrectomy and esophagogastric anastomosis with digestive tract reconstruction using the esophagogastric biological muscle flap. Observation indicators: (1) surgical situations and early complications; (2) follow-up and late com-plications. Measurement data with normal distribution were represented as Mean± SD, and measure-ment data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations and early complications. All 10 patients success-fully completed the surgery without conversion to open surgery, and the operation time was (166±18)minutes. Cases with digestive tract reconstruction as end-to-side anastomosis and Overlap anas-tomosis were 1 and 9, respectively. The time of digestive tract reconstruction, the number of lymph node dissected, volume of intraoperative blood loss, time to postoperative first anal exhaust, time to postoperative first intake of liquid food, duration of postoperative hospital stay were (40±12)minutes, 24±6, (41±9)mL, (3.4±0.5)days, (4.1±1.0)days, (8.3±0.7)days in the 10 patients. Of 4 cases with postoperative early complications, 1 case developed pulmonary infection (Clavien-Dindo grade Ⅱ) on the second day after surgery, with pulmonary infection absorbed after 5 days of antibiotic treat-ment. Two cases experienced chest distress and shortness of breath on the third day after surgery, with the diagnosis of a small to moderate amount of pleural effusion after chest B-ultrasound examination. After pleural puncture and active treatment, the symptoms of them were improved and the pleural effusion disappeared. There was 1 case with choking sensation when eating solid food, which was started from the third week after surgery. Upper gastrointestinal imaging revealed mild anastomotic stenosis of Clavien-Dindo grade Ⅰ in the patient, who was improved after conservative treatment. On the 7th day after surgery, all 10 patients underwent upper gastrointestinal angiography, and no anastomotic leakage or stenosis occurred. There was no sign of contrast agent reflux in the supine position and 30° head down position. (2) Follow-up and late complications. All 10 patients were followed up for 59.5(range, 31.0-127.0)days. The esophageal reflux scale score of 10 patients was 1.4±0.3. During the follow-up, 1 case underwent gastroscopy on 40 days after surgery, which showed reflux esophagitis with Los Angeles grade as B and the Clavien-Dindo grade as Ⅰ. There was no clinical symptom such as heartburn or acid reflux. Results of 24-hour pH monitoring showed that the patient experienced 24 instances of reflux in an upright position and 15 instances of reflux in a supine position, with no prolonged reflux. The total reflux time within 24 hours was 75 minutes. The DeMeester score was 38.3. Results of esophageal pressure measurement showed that the esophageal contraction morphology was normal, but the anastomotic opening was not well relaxed. The rest of 9 cases had no complication such as reflux esophagitis.Conclusion:Biological muscle flap applied in the laparoscopic radical proximal gastrectomy with esophagogastric anastomosis is safe and feasible, with satisfied short-term efficacy.

Objective:To investigate the efficacy of trimetazidine in the treatment of atrial arrhythmias in patients with ischemic cardiomyopathy and heart failure and analyze the effect of trimetazidine on cardiac function and atrial arrhythmias.Methods:A total of 79 patients with ischemic cardiomyopathy and heart failure who received treatment at the Second Hospital of Jiaxing from December 2018 to June 2020 were included in this study. These patients were randomly divided into an observation group ( n = 41) and a control group ( n = 38). Patients in the control group received conventional drugs, while those in the observation group received trimetazidine sustained-release tablets twice daily, each time taking 35 mg in addition to conventional drugs. The treatment lasted for 24 weeks. Before and after treatment, cardiac function indicators (left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance), cardiac color Doppler ultrasound indicators [ratio of early to late peak filling rate (E/A ratio)], left ventricular fractional shortening), electrocardiogram parameters (maximum P-wave duration, minimum P-wave duration, and P-wave dispersion), dynamic electrocardiogram parameters [number of single atrial premature beats, total number and duration of paroxysmal atrial tachycardia episodes, total number and duration of paroxysmal atrial flutter/fibrillation attacks, standard deviation of RR intervals, root mean square of successive differences between normal heartbeats, proportion of successive RR intervals that differ by more than 50 ms divided by the total number of NN intervals (PNN50), standard deviation of average NN intervals, high frequency and low frequency], as well as changes in high sensitivity C-reactive protein were analyzed in each group. Results:After treatment, left ventricular ejection fraction, B-type brain natriuretic peptide, 6-minute walking distance, maximum P-wave duration, P-wave dispersion, total number of atrial flutter/atrial fibrillation attacks, and duration of atrial flutter/atrial fibrillation in the observation group were (51.05 ± 7.68)%, (1 615.59 ± 1 129.78) ng/L, (350.02 ± 62.99) m, (99.73 ± 11.60) ms, (22.44 ± 12.03) ms, (0.22 ± 0.61), and (4.59 ± 12.30) minutes, respectively, which were significantly superior to (46.82 ± 7.34)%, (2 267.47 ± 1 539.03) ng/L, (294.16 ± 58.20) m, (111.71 ± 10.00) ms, (36.77 ± 15.07) ms, (0.76 ± 1.13), (15.66 ± 22.30) minutes in the control group, t = -2.95, 2.16, -4.08, 4.89, 4.68, 2.69, 2.76, all P < 0.01). Conclusion:Trimetazidine can effectively reduce atrial arrhythmias and improve the prognosis of patients with ischemic cardiomyopathy and heart failure, which warrants clinical promotion.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Objective This study aims to investigate the current status of burnout among anesthesi-ology residents,and to explore its influencing factors and potential interventions.Methods A total of 2 651 practicing anesthesiology residents from 218 hospitals nationwide were included in this study.Demographic characteristics,occupational features,and psychological resilience scores(Connor-Davidson resilience scale)were collected using a questionnaire distributed electronically.The Maslach burnout inventory-human service survey(MBI-HSS)was used to assess burnout.A comparison between groups with and without occu-pational burnout was conducted.Multiple logistic regression analysis was used to identify risk factors for burnout among anesthesiology residents.Results Out of the expected 2 651 questionnaires,1 990 valid responses were received(response rate 77.7%).The prevalence of burnout among the residents was 53.4%(1 063/1 990).Compared with residents without occupational burnout,those with burnout had a signifi-cantly higher proportion of females,working in tertiary hospitals,unmarried individuals,frequency of en-countering challenging patients,participating in on-call duty,and research tasks,and had a significantly lon-ger weekly working hours(P＜0.05).Multivariate logistic regression analysis indicated that female(OR = 1.58,95%CI 1.28-1.97,P＜0.01),longer working hours(OR = 1.62,95%CI 1.45-1.81,P＜0.01),and higher frequency of encountering challenging patients(OR = 1.11,95%CI 1.11-1.40,P＜0.01)were risk factors for occupational burnout.High levels of psychological resilience was protective factor against burnout(OR = 0.86,95%CI 0.84-0.88,P＜0.01).Conclusion The occurrence of burnout among anesthesiology residents is high.It is crucial to focus on and design practical preventive measures to en-hance psychological resilience,ensuring healthy physical and mental development of the resident community.