This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

OBJECTIVE: By analyzing the hormone secretion of the adenohypophysis, thyroid glands, gonads, and adrenal cortex in patients with hematological diseases before and after hematopoietic stem cell transplantation (HSCT), this study aims to preliminarily explore the effect of HSCT on patients' hormone secretion and glandular damage. METHODS: The baseline data of 209 hematological disease patients who underwent HSCT in our hospital from January 2019 to December 2023, as well as the data on the levels of hormones secreted by the adenohypophysis, thyroid glands, gonads and adrenal cortex before and after HSCT were collected, and the changes in hormone levels before and after transplantation were analyzed. RESULTS: After allogeneic HSCT, the levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3) and estradiol (E2) decreased, while the levels of luteinizing hormone (LH) and follicle- stimulating hormone (FSH) increased. The T3 level of patients with decreased TSH after transplantation was lower than that of those with increased TSH after transplantation. In female patients, the levels of prolactin (PRL), progesterone (Prog), and testosterone (Testo) decreased after HSCT. Testo and PRL decreased when there was a donor-recipient sex mismatch, and the levels of adrenocorticotropic hormone (ACTH) and cortisol (COR) decreased when the HLA matching was haploidentical. The levels of T3, FT3, and PRL decreased after autologous HSCT. In allogeneic HSCT patients, the levels of TSH, T4, T3, FT3, and ACTH in the group with graft-versus-host disease (GVHD) were significantly lower than those in the group without GVHD. Logistic regression analysis showed the changes in hormone levels after transplantation were not correlated with factors such as the patient's sex, age, or whether the blood types of the donor and the recipient are the same. CONCLUSION HSCT can affect the endocrine function of patients with hematological diseases, mainly affecting target glandular organs such as the thyroid, gonads, and adrenal glands, while the secretory function of the adenohypophysis is less affected.
Humans ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Hematologic Diseases/blood* ; Follicle Stimulating Hormone/blood* ; Triiodothyronine/blood* ; Luteinizing Hormone/blood* ; Thyroid Gland/metabolism* ; Estradiol/blood* ; Thyrotropin/blood* ; Gonads/metabolism* ; Adult ; Middle Aged ; Adrenocorticotropic Hormone/blood* ; Hormones/metabolism* ; Adrenal Cortex/metabolism* ; Prolactin

OBJECTIVE: The relationship between fish consumption and stroke is inconsistent, and it is uncertain whether this association varies across predicted stroke risks. METHODS: A cohort study comprising 95,800 participants from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China project was conducted. A standardized questionnaire was used to collect data on fish consumption. Participants were stratified into low- and moderate-to-high-risk categories based on their 10-year stroke risk prediction scores. Hazard ratios ( HRs) and 95% confidence intervals ( CIs) were estimated using Cox proportional hazard models and additive interaction by relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI). RESULTS: During 703,869 person-years of follow-up, 2,773 incident stroke events were identified. Higher fish consumption was associated with a lower risk of stroke, particularly among moderate-to-high-risk individuals ( HR = 0.53, 95% CI: 0.47-0.60) than among low-risk individuals ( HR = 0.64, 95% CI: 0.49-0.85). A significant additive interaction between fish consumption and predicted stroke risk was observed (RERI = 4.08, 95% CI: 2.80-5.36; SI = 1.64, 95% CI: 1.42-1.89; AP = 0.36, 95% CI: 0.28-0.43). CONCLUSION Higher fish consumption was associated with a lower risk of stroke, and this beneficial association was more pronounced in individuals with moderate-to-high stroke risk.
Humans ; China/epidemiology* ; Male ; Female ; Stroke/etiology* ; Middle Aged ; Prospective Studies ; Incidence ; Aged ; Animals ; Fishes ; Risk Factors ; Diet ; Seafood ; Adult ; Cohort Studies

ObjectiveTo genotype Oncomelania hupensis， based on microsatellites， in different snail-bearing environments in Jiaxing City， Zhejiang Province， for population genetics analysis in order to explore the reasons and influencing factors for the existence or proliferation of snails and to provide scientific basis for effective monitoring and control of snails. MethodsA total of 90 snail samples from three populations were collected in Yaobang Village （YB） and Sanxing Village （SX） in Pinghu City， and Yunhe Farm （YH） in Xiuzhou District， all were selected for snail checking in key snail habitats of Jiaxing City in 2022. DNA of the snails was genotyped and analyzed for population genetics using nine microsatellite loci. ResultsA total of 84 alleles were observed， and the mean number of alleles （Na） was 7.889， 5.667， and 3.778 for YB， SX， and YH respectively； the number of effective alleles （NeA） was 4.807， 3.329， and 2.294， respectively； and the coefficients of inbreeding （F_IS） were 0.400， 0.377， and 0.493， respectively. Under the Infinite Allele Model （IAM）， the SX and YH might have a recent bottleneck. The NEstimator and LDNe software calculated effective population sizes （Ne） were above 31.9. AMOVA analysis showed that the variation of snails in the three populations mainly existed among individuals， accounting for 41.4% of the total variation. The value of the index of genetic differentiation between populations （F_ST） was 0.286， indicating a high degree of genetic differentiation. The results of the principal component analysis and phylogenetic tree were consistent， and the three populations were divided into two lineages， YB and SX were one lineage， and YH belonged to another independent lineage. Population history and dynamics analysis showed that the gene flow of the three populations was insufficient， population divergence history indicated that YH might have diverged from SX first， and YB was produced by the contact fusion of SX and YH. ConclusionThe genetic diversity of snail populations in Jiaxing City is generally low， and the snail populations are unstable， with a great degree of genetic differentiation and insufficient gene flow among populations. This study can provide a basis for evaluating the effectiveness of the control of the snail as well as monitoring the trend of the spread of the snail.

Objective:To explore the onset characteristics and pathophysiological changes of simple liver cyst in Beijing.Methods:A retrospective cohort study was used. The physical examination data of Department of Health Management of Xuanwu Hospital of Capital Medical University for 10 years from January 1, 2012 to December 31, 2021 were analyzed. Selected clinical data of 37 389 subjects with 2 or more repeated ultrasound examinations, including 17 759 males, 19 630 females, aged (44.4±16.2) years, ranged from 22-103 years. 3 431 cases hepatic cyst were confirmed by repeated ultrasound examination, the data of the liver cyst formation after the same physical examination were the study group ( n=3 431), and the data before cyst formation were the control group ( n=3 431). The observation indicators included: (1) the epidemiological characteristics of liver cysts; (2) the age distribution of the incidence of liver cysts; (3) the gender distribution of the incidence of liver cysts; (4) the pathophysiological changes of liver cysts.Measurement data of normal distribution were expressed as mean±standard deviation ( ± s). The measurement data of skewed distribution were expressed as M ( Q1, Q3), using Wilcoxon signed rank sum test for comparing groups and chi-square test for comparing count data. The factors associated with hepatic cyst pathogenesis were summarized by multivariate Logistic regression. Results:The overall incidence of hepatic cysts was 9.18%, 9.78% in males, 8.63% in females, and the incidence of males was greater than that of females. The incidence of males over 70 to 79 years old decreased slightly, and the incidence in males and females in the other age groups increased with age.Results of multivariate Logistic analysis showed age ( OR=1.01, 95% CI: 1.01-1.02, P<0.01), waist circumference( OR=1.02, 95% CI: 1.01-1.02, P<0.01), systolic blood pressure ( OR=1.00, 95% CI: 0.99-1.00, P=0.013), ALT ( OR=0.99, 95% CI: 0.98-1.00, P<0.01), AST ( OR=1.03, 95% CI: 1.02-1.04, P<0.01), triglyceride lipids ( OR=0.90, 95% CI: 0.86-0.95, P<0.01), HDL( OR=0.71, 95% CI: 0.60-0.83, P<0.01), uric acid ( OR=1.00, 95% CI: 1.00-1.00, P<0.01), creatinine ( OR=0.99, 95% CI: 0.99-0.99, P<0.01) were the factors influencing the occurrence of liver cysts. Conclusions:The incidence of liver cysts increased linearly with age, and the incidence of males was greater than that of females. Age, waist circumference, systolic blood pressure, ALT, AST, triglycerides, HDL, uric acid, and creatinine may interact with the occurrence and development of liver cysts.

Sarcopenia and physical deconditioning are common complications in patients with liver cancer,which are frequently caused by insufficient physical activity and poor nutritional status,resulting in physical frailty and a significant impact on the patient's physical fitness.Notably,sarcopenia,frailty,and poor cardiopulmonary endurance have all been linked to higher mortality rates among patients with liver cancer.Exercise intervention significantly improves various health parameters in liver cancer patients,including metabolic syndrome,muscle wasting,cardiorespiratory endurance,health-related quality of life,and reduction in hepatic venous pressure gradient.However,the link between physical exercise and liver cancer is commonly overlooked.In this article,we will examine the impact of exercise on liver cancer and present the most recent evidence on the best types of exercise for various stages of liver cancer.This article also summarizes and discusses the molecular mechanisms that control metabolism and systemic immune function in tumors.In brief,physical exercise should be considered an important intervention in the prevention and treatment of liver cancer and its complications.

Objective To explore the clinical characteristics and death factors of elderly male with type 2 diabetes mellitus(T2DM)complicated with coronavirus infectious disease 2019(COVID-19).Methods A total of 55 hospitalized elderly male T2DM patients with COVID-19 were enrolled in this study from December 2022 to February 2023.All the patients were divided into survival group(n=32)and death group(n=23).The clinical indicators were compared between the two groups and evaluated by multifactor analysis to clarify their clinical characteristics and death risk factors.Results Age,T2DM duration,C-RP,procalcitonin,serum creatinine,creatine kinase,myoglobin,BNP,troponin,D-dimer,FPG and HbA1c were higher(P＜0.05 or(P＜0.01),while lymphocyte count and PaO2 were lower(P＜0.05)in death group than in survival group.The advanced age,C-RP,procalcitonin,serum creatinine,troponin,BNP,D-dimer,increase of FPG and HbA1c,and the reduction of lymphocyte count and PaO2 were risk factors for death(P＜0.05).Conclusion Age,blood glucose control,cardiac renal and pulmonary functions,and risk of thrombosis in elderly male T2DM with COVID-19 have important significance inevalu-ating the prognosis.

Objective:To investigate the effect of sertraline hydrochloride combined with compound chamomile lidocaine gel in the treatment of premature ejaculation(PE).Methods:We selected 80 cases of PE treated in our hospital from June 2021 to May 2023 and equally randomized them into a control and an observation group,the former medicated with compound chamomile lidocaine gel while the latter with sertraline hydrochloride in addition,both for 6 weeks.We recorded and compared the intravaginal ejaculation latency time(IELT),the number of successful sexual intercourses per week,the Premature Ejaculation Diagnostic Tool(PEDT)scores,and the incidence of adverse reactions between the two groups of patients.Results:After the treatment,the IELT was signif-icantly longer([5.39±1.17]vs[2.49±0.73]min,P＜0.05),the weekly number of successful sexual intercourses remarkably higher(1.82±0.45 vs 0.93±0.19,P＜0.05)and the PEDT scores markedly lower(7.42±2.04 vs 9.85±2.36,P＜0.05)in the observation than in the control group,but no statistically significant differences were observed in the baseline PEDT scores or the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:Sertraline hydrochloride combined with com-pound chamomile lidocaine gel is definitely effective in the treatment of PE,which can significantly improve the patients'quality of sexual life,with a high safety and low incidence of adverse reactions.

Objective: To perform an epidemiological survey of the first case with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Pinghu City of Jiaxing City, Zhejiang Province on March 13, 2022, so as to provide insights into the management of coronavirus disease (COVID-19) epidemics. Methods: According to the requirements of the Protocol on Prevention and Control of COVID-19 (8th Edition), epidemiological investigations were performed among 39 cases with SARS-CoV-2 infections in Pinghu City from March 13 to 20, 2022. Cases' demographics, clinical symptoms, history of immunization and exposure were collected, and close contacts were identified. Pharyngeal swabs were sampled from infected cases for detection of SARS-CoV-2 nucleic acid and whole-genome sequencing, and the source of infection and transmission route were investigated. Results: The index case for this COVID-19 epidemic was an imported case from Shanghai Municipality, who infected 6 persons via aerosol transmission when playing in the badminton venue of Pinghu National Fitness Center on March 9; subsequently, one of these infected cases infected another 18 persons when playing in the badminton venue of Jiadian Village Resident's Fitness Center in Zhapu Township on March 12. Sixteen confirmed cases were reported, and all cases were mild; another 23 asymptomatic cases were diagnosed, with no death reported. This epidemic occurred from March 11 to 20, with 3 generations of spread and a median incubation period of 3 days. The SARS-CoV-2 infected cases had a median age of 33.5 (interquartile range, 12.0) years and included 36 cases with a history of COVID-19 vaccination. There were 16 cases with fever, cough, runny nose and sore throat, and 13 cases with imaging features of pneumonia. The effective reproductive number (Rt) of the COVID-19 epidemic was 7.73 at early stage, and was less than 1 since March 21. Whole-genome sequencing identified Omicron BA.2 variant among 33 cases, which had high homology with the index cases. Conclusion This epidemic was a cluster of COVID-19 caused by imported Omicron BA.2 variant infection from Shanghai Municipality, and the COVID-19 transmission was mainly caused by indoor aerosols.

Objective:To explore the clinical efficacy of a retrograde pubic ramus intramedullary nail (RPRIN) in the treatment of anterior pelvic ring fractures.Methods:A retrospective study was conducted to analyze the 14 patients with anterior pelvic ring fracture who had been treated and followed up at Department of Traumatic Surgery, Tongji Hospital From June 2020 to February 2021. There were 10 males and 4 females with an age of (44.8±12.5) years. By the AO/OTA classification for pelvic fractures, 5 cases were type 61-A, 4 cases 61-B, and 5 cases type 61-C; by the Nakatani classification, 1 case belonged to unilateral zone Ⅰ fracture, 5 cases to unilateral zone Ⅱ fracture, 2 cases to unilateral zone Ⅲ fracture, 3 cases to right zone Ⅱ and left zone Ⅲ fracture, 2 cases to zone Ⅲ fracture on both left and right sides, and 1 case to zone Ⅱ fracture on both sides. The time from injury to operation was (7.8±1.8) days. All the anterior pelvic ring fractures were fixated with a RPRIN. The time and fluoroscopic frequency for placement of every single RPRIN, quality of fracture reduction, and pelvic function and incidence of postoperative complications at the last follow-up were recorded.Results:A total of 18 RPRINs were placed in the 14 patients. For placement of each RPRIN, the time was (35.9±8.6) min, and the fluoroscopic frequency (22.8±1.9) times. No complications such as infection occurred at any surgical incision after RPRIN placement. According to the Matta scoring, the quality of postoperative fracture reduction was assessed as excellent in 7 cases, as good in 5 cases and as fair in 2 cases. The 14 patients were followed up for (18.1+1.5) months. Their X-ray and CT images of the pelvis at the last follow-up showed that the fractures healed well and the intramedullary nails were placed in the cortical bone of the anterior ring of the pelvis. According to the Majeed scoring at the last follow-up, the pelvic function was assessed as excellent in 10 cases, as good in 3 cases and as fair in 1 case. One patient reported discomfort during squatting 2 months after operation but the symptom improved 3 months later without any special treatment. No patient experienced such complications as displacement or slippage of RPRIN, or pain at the insertion site.Conclusion:RPRIN is effective in the treatment of anterior pelvic ring fractures, showing advantages of small surgical incision, limited intraoperative fluoroscopy and short operation time.