This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals ; Isoproterenol/adverse effects* ; Male ; Mice ; Signal Transduction/drug effects* ; Vanillic Acid/administration & dosage* ; Dynamins/genetics* ; Mice, Inbred C57BL ; Fibrosis/genetics* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Myocardium/metabolism* ; Humans

OBJECTIVE: To investigate short-term effectiveness of robot-assisted fracture reduction and fixation combined with arthroscopic exploration for posterolateral depressed tibial plateau fractures. METHODS: Between January 2022 and January 2024, 8 patients with posterolateral depressed tibial plateau fractures (Schatzker type Ⅲ) were treated using robot-assisted fracture reduction and fixation combined with arthroscopic exploration, with simultaneous treatment of concomitant ligament or meniscus tears. There were 3 males and 5 females with an average age of 54.1 years (range, 42-68 years). Injury mechanisms included traffic accidents (3 cases) and falls (5 cases). The time from injury to operation ranged from 2 to 4 days (mean, 3.1 days). Operation time, intraoperative blood loss, hospital stay duration, visual analogue scale (VAS) score for pain, and complications were recorded. Fracture healing and knee Rasmussen scores were assessed radiographically, while knee function was evaluated using range of motion and Hospital for Special Surgery (HSS) scores. RESULTS: All operations were successfully completed. The operation time was 108-129 minutes (mean, 120.1 minutes). The intraoperative blood loss was 10-100 mL (mean, 41.3 mL). The hospital stay duration was 4-7 days (mean, 5.6 days). All incisions healed by first intention without complication such as peroneal nerve injury, vascular damage, or infection. All patients were followed up 32-48 weeks (mean, 40 weeks). Radiographic follow-up confirmed that the knee Rasmussen scores rated as excellent in 8 patients and all fractures healed with the healing time of 12-16 weeks (mean, 13.5 weeks). The VAS score for pain was 2-4 (mean, 2.8) at discharge and improved to 0 at 1 month after operation. The knee range of motion was 80°-110° (mean, 96.1°) at discharge and increased to 135°-140° (mean, 137.9°) at 1 month after operation. At 3 months after operation, the HSS score was 91-94 (mean, 92.8), all graded as excellent. No severe complication, including implant failure, occurred during follow-up. CONCLUSION For posterolateral depressed tibial plateau fractures, the minimally invasive approach combining robot-assisted fracture reduction and fixation with arthroscopic exploration demonstrates multiple advantages, including shorter operation time, reduced intraoperative blood loss, excellent wound healing, fewer complications, and rapid recovery of knee function. This technique achieves satisfactory short-term effectiveness, while its long-term effectiveness requires further evaluation.
Humans ; Male ; Tibial Fractures/surgery* ; Female ; Middle Aged ; Adult ; Arthroscopy/methods* ; Minimally Invasive Surgical Procedures/methods* ; Fracture Fixation, Internal/methods* ; Aged ; Treatment Outcome ; Robotic Surgical Procedures/methods* ; Operative Time ; Range of Motion, Articular ; Fracture Healing ; Length of Stay ; Tibial Plateau Fractures

Objective To assess the effectiveness of the evaluation of military physical function(EMPF)system in predicting the occurrence of military training injuries among new recruits to provide scientific guidance and methodological choice for military training.Methods A total of 527 new recruits from 5 grassroots units from July 2016 to February 2018 were selected for the study.The recruits underwent EMPF testing,and their military training injuries were monitored over a 2-year follow-up period.Those who sustained injuries during training were divided into injury group(n=163),while the remaining recruits were placed in healthy group(n=364).The predictive ability of the total EMPF score for training injuries was assessed using the receiver operating characteristic curve(ROC),and the correlation between the total EMPF score,individual test scores,and military training injuries were analyzed using binary logistic regression.Results The total EMPF score of new recruits in injury group(19.52±1.97)was significantly lower than that of healthy group(24.31±1.54)(P<0.001),which also demonstrated a high diagnostic value in predicting the risk of military training injuries,with an area under the curve(AUC)of ROC of 0.971(P<0.001).A cut-off value of 22 scores was found to have the highest accuracy in predicting future training injuries,with an odds ratio(OR)of 25.63,sensitivity of 0.939,specificity of 0.879,positive likelihood ratio of 7.76,and a post-test probability of 0.67.Binary logistic regression analysis revealed that 6 EMPF tests,including holding the ball over and leaning back,bending forward and touching the ground with the ball,lunge squat and twist,swallow balance with holding the ball afterward,vertical jump,and respiratory pattern assessment,were negatively associated with the risk of military training injuries(P<0.0001).Conclusion The EMPF system can effectively predict the risk of military training injuries,with military personnel whose total EMPF score is less than 22 being at higher risk of sustaining such injuries.

Objective:To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization (MR) method.Methods:Single nucleotide polymorphisms (SNP) strongly associated with 91 plasma inflammatory proteins in genome-wide association studies (GWAS) were used as instrumental variables, and liver cirrhosis was used as the outcome variable. Random-effects inverse variance-weighted (IVW), MR Egger regression, odds ratio ( OR) and its 95% confidence interval were used to evaluate the causal relationship. Simultaneously, sensitivity analysis was performed using MR pleiotropy residuals and outliers (MR-PRESSO) and the Q-test. Results:The causal relationship between the expression of seven specific circulating inflammatory proteins and liver cirrhosis was confirmed by the inverse variance-weighted (IVW) method. The results showed that five plasma inflammatory proteins, including leukemia inhibitory factor [ OR( CI)=0.66, P=9.73×10 -5], interleukin-18 [ OR( CI)=0.76, P=0.013], tumor necrosis factor ligand superfamily member 12[ OR( CI)=0.75, P=0.024], monocyte chemoattractant protein 2 [ OR( CI)=0.89, P=0.036], and C-C motif chemokine 25 [ OR( CI)=0.84, P=0.039], were negatively correlated with cirrhosis and were protective factors for cirrhosis. T cell surface glycoprotein CD5 [ OR ( CI)=1.29, P=0.035] and C-X-C motif chemokine 10 [ OR( CI)=1.32, P=0.043] were positively correlated with cirrhosis and were risk factors for cirrhosis. The results of the MR-PRESSO, Q-test, MR-Egger intercept test, and leave-one-out method all showed the stability. Conclusion:The research results indicated that the increased levels of leukemia inhibitory factor, interleukin-18, tumor necrosis factor ligand superfamily member 12, monocyte chemoattractant protein-2, and C-C motif chemokine 25 were protective factors in the development of cirrhosis, while the increased levels of T cell surface glycoprotein CD5 and C-X-C motif chemokine 10 were risk factors for the development of cirrhosis based on genetic data.

Objective : To investigate the effects of sinapine on lung tissue inflammation and mucus hypersecretion in asthmatic mice. Methods: Eight-week-old female C57BL/6J mice were randomly divided into Control group, ovalbumin(OVA) group, Sinapine group, and Sinapine+OVA group. The asthmatic mice model were established by intraperitoneal injection of OVA combined with aluminum hydroxide [Al(OH)3] suspension and OVA nasal stimulation. One hour before OVA nasal stimulation, the mice in Sinapine+OVA group and Sinapine group were intraperitoneally injected with sinapine solution, and the mice in OVA group and Control group were treated with the same dose of 0.9% sodium chloride solution. 24 hours after the last OVA stimulation, the inflammation of lung tissue of mice were observed by HE staining; the mucus secretion were evaluated by PAS staining; the mRNA expression levels of Interleukin-4(IL-4), Interleukin-5(IL-5), Interleukin-13(IL-13), tumor necrosis factor-alpha(TNF-α), Mucin 5ac(Muc5ac), and the mRNA of the key genes of Notch pathway such as Notch receptor 1(Notch1), Notch receptor 2(Notch2), Notch receptor 3(Notch3), and hes family bHLH transcription factor 1(Hes1) in lung tissues were detected by real-time fluorescent quantitative PCR(RT-qPCR); the expression levels of Notch1, Notch2, Notch3 and Hes1 proteins were determined by Western blot. Results : Compared with Control group, the inflammation score and PAS score of lung tissues of mice in OVA group increased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in OVA group were enhanced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in OVA group significantly increased(P<0.001), while there was no significant difference in the mRNA and protein expression levels of Notch1. Compared with OVA group, the inflammation score and PAS score of lung tissues of mice in Sinapine+OVA group decreased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in Sinapine+OVA group were reduced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in Sinapine+OVA group were downregulated(P<0.05), while there was no significant difference in the mRNA and protein expression levels of Notch1. Conclusion Sinapine can alleviate the lung tissue inflammation and mucus hypersecretion in asthmatic mice, and its mechanism may be related to the inhibition of Notch2/Notch3-Hes1 signal pathway.

Objective:To explore the application effect of interventional teaching in undergraduate nursing internship in operating rooms.Methods:A total of 98 undergraduate nursing students who worked as interns in the operating room during the two school years from June 2022 to February 2024 were selected as research subjects. Students who entered the program from June 2022 to February 2023 were enrolled into control group (50 students), and those who entered from June 2023 to February 2024 were enrolled into experimental group (48 students). The students conducted their internships in batches (with 4 to 5 students per subgroup) following a departmental rotation mechanism. The control group received routine teaching, while the experimental group received interventional teaching. At the end of the internship, the two groups were compared for their performance, including basic and specialized knowledge, skills, theory, and operation; patient reception, tripartite verification, and intraoperative cooperation for planned video-assisted thoracoscopic bullectomy; and their degrees of satisfaction with the teaching. The t-test was performed using SPSS 26.0. Results:The experimental group achieved significantly higher theoretical scores than the control group [(91.69±4.51) vs. (74.52±6.06)]. Meanwhile, the experimental group was significantly superior to the control group in operational performance, including surgical hand disinfection [(96.08±1.93) vs. (92.14±3.07)] and wearing and removing sterile surgical gowns and sterile gloves [(97.00±1.75) vs. (94.10±3.48)). In terms of specialized knowledge and skills, specifically, patient reception and third-party verification in simulated surgical nursing, the experimental group achieved higher scores than the control group [(98.77±0.69) vs. (94.04±2.56); (98.54±0.65) vs. (94.64±2.65)]. In terms of intraoperative cooperation, the experimental group showed a slight advantage over the control group. The experimental group had higher degrees of satisfaction with teaching than the control group, including course design, implementation methods, course arrangement, teaching attitude, teaching methods, degree of participation, gains, and assistance.Conclusions:After adopting interventional teaching, the teaching effect for nursing internship in operating rooms is better. It improves the various assessment scores of nursing students, enhances their comprehensive abilities and degrees of satisfaction with teaching, and reinforces the teaching abilities in operating rooms.

Objective To analyze the characteristics of death cases in a certain tertiary hospital,providing references for hospital management decisions and the evaluation of the effectiveness of medical services.Methods The information of death ca-ses of inpatients in the hospital from 2019 to 2023 was extracted through the inpatient medical records information system,and the medical records of inpatients were retrospectively analyzed by clinical epidemiological methods.Results The cumulative number of inpatients admitted to the hospital from 2019-2023 was 459 821,with 3 250 deaths and a case-fatality rate of 0.71％.There was a decreasing trend in the case fatality rate from 0.71％in 2019 to 0.63％in 2023,but the difference was not statistically significant(APC=-3.17,P＞0.05).The case fatality rate was 0.97％for males and 0.45％for females,with males having a higher case fatality rate than females(x2=435.206,P＜0.05).The mean age of the deceased cases was(69.59±17.70)years,and the case fatality rate increased gradually with age,and the highest case fatality rate was 2.98％in the age group of ≥80 years.The difference in case fatality rate between patients of different age groups was statistically significant(x2=3 502.991,P＜0.05).The top 5 causes of death of hospitalized patients were tumor,circulatory diseases,respiratory diseases,some infec-tious and parasitic diseases and injuries,poisoning and external causes,accounting for 87.33％of the total deaths.The main causes of death in neoplasms were bronchial and pulmonary malignancies,hepatic and intrahepatic biliary malignancies,and gas-tric malignancies;in the circulatory diseases,cerebral infarction,acute myocardial infarction,and intracerebral haemorrhage;and in the respiratory diseases,pathogens unspecified pneumonias,bacterial pneumonias,and other chronic obstructive pulmona-ry diseases.Conclusion The case fatality rate of male and ≥80 years old patients in this hospital is higher.Tumor,circulatory diseases and respiratory diseases are the main causes of death.The hospital should allocate medical resources in a scientific and reasonable way according to the age,gender and disease characteristics of the patients;strengthen the prevention and treatment of tumors,circulatory diseases and respiratory diseases according to the cause of death and their distribution,improve the diagnosis and treatment level,and reduce the inpatient morbidity and fatality rate.