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*

Objective:To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass.Methods:This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People′s Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period.Results:The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of ( M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation ( OR=11.424, 95% CI: 1.477 to 144.564, P=0.033) and excessive rewarming ( OR=15.249, 95% CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions:The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

Objective:A subunit vaccine against SARS-CoV-2 BA.2 variant was prepared by prokaryotic expression system and its immunogenicity was evaluated.Methods:The recombinant plasmid of BA.2 variant RBD and the tandem of RBD and TT-P2 epitopes was constructed by molecular cloning technology, and recombinant proteins So and Sot were obtained by protein purification technology. Mice were immunized by intramuscular injection after mixing protein So/Sot as immunogens with Al(OH) 3 adjuvant to evaluate the effect of cellular and humoral immunity. Results:High purity soluble protein were obtained by dialysis and renaturation after expressed by prokaryotic system. The number of antigen-specific T lymphocytes secreting IFN-γ and IL-4 (213.7±0.6 and 311.7±1.5) in the Sot group induced by mice was significantly higher than that in the So group (94.3±16.8 and 185.7±4.2) ( P<0.001). The serum antibody level induced by Sot group was higher than that in the So group, the geometric mean titer (GMT) of neutralizing antibodies against BA.2 strain were 588 and 337, respectively ( P<0.05). Sot protein induced Th1/Th2 mixed type immune response with the predominance of Th2 type. Conclusions:The protein subunit vaccine expressed by the prokaryotic system have excellent cellular and humoral immunogenicity, which provides a strong theoretical basis for the development of the protein subunit vaccines of the SARS-CoV-2 Omicron variant.

Objective:To study the immunotherapeutic effect of chimeric hepatitis B core protein virus-like particles in subcutaneous lung adenocarcinoma mouse model, lays the foundation for the progression of tumor nano-therapeutic technology development.Methods:The plasmid was constructed by inserting a B-cell epitope of the human epidermal growth factor receptor-2 (HER-2) at hepatitis B core protein′s major immunodominant region (MIR). The recombinant virus nanoparticle, denoted as HBc-HER2, was obtained by E. coli expression system, followed by a series of purification steps. The immune response to this recombinant protein nanoparticle was assessed by measuring levels of anti-HER-2 antibody levels and characterizing antibody isotypes in a subcutaneous tumor mice model of lung adenocarcinoma. While tumor therapeutic efficacy was evaluated by measuring tumor size changes with an electronic caliper and MRI photography of subcutaneous tumor in mice.Results:A high-purity HBc-HER2 recombinant protein was obtained and could assemble into nanoparticle. Animal studies had demonstrated the robust immunogenicity of this vaccine in inducing high levels of HER-2 specific antibodies, yielding positive therapeutic outcomes against tumors.Conclusions:The engineered HBc-HER2 demonstrated notable tumor therapy efficacy in a subcutaneous lung adenocarcinoma mouse model, offering a foundation for tumor therapeutic nanotechnology vaccine research.

Objective:To examine the therapeutic strategy and its impacting factors by analyzing the perioperative outcomes of total thoracoscopic repeat mitral valve surgery under moderate hypothermia-induced ventricular fibrillation with cardiopulmonary bypass.Methods:This study is a retrospective case series. Totally 63 patients who underwent repeat mitral valve surgery by the same surgeon from January 2021 to December 2023 in Department of Cardiovascular Surgery, the First Medical Center of People′s Liberation Army General Hospital were retrospectively enrolled. There were 28 males and 35 females with an age of (58.3±15.9) years (range: 13 to 84 years). Surgery was performed using a totally thoracoscopic approach under moderate hypothermia-induced ventricular fibrillation. Mitral valvuloplasty was completed in 32 cases and mitral valve replacement in 31 cases. Preoperative baseline data and perioperative outcomes of the patients were collected and Logistic regression was used to analyze independent influencing factors of premature ventricular contractions in the early postoperative period.Results:The intraoperative cardiopulmonary bypass time was (191.5±50.9) minutes (range: 95 to 286 minutes), and the hypothermic ventricular fibrillation time was (99.0±39.8) minutes (range: 34 to 203 minutes). The anal temperature before the start of cardiopulmonary bypass was (36.3±0.5) ℃ (range: 35.2 to 38.0 ℃), the lowest intraoperative anal temperature was (27.3±1.3) ℃(range: 23.7 to 30.1 ℃), and the anal temperature at the time of the cessation of cardiopulmonary bypass was (36.3±0.4) ℃ (range: 35.2 to 37.0 ℃), and excessive rewarming was observed in 33 cases. Six cases applied the artificial heart assist device. Seventeen cases developed premature ventricular contractions in the early postoperative period. Two cases developed neurologic complications. Five cases developed respiratory complications. One case developed urological systemic complications. Six cases were mechanically ventilated for more than 3 days, and the duration of ICU stay in 16 cases was more than 3 days and the postoperative discharge time of ( M(IQR)) 8.0 (3.5) days (range: 3 to 26 days). Two cases died or were discharged voluntarily. Logistic regression results showed that persistent preoperative atrial fibrillation ( OR=11.424, 95% CI: 1.477 to 144.564, P=0.033) and excessive rewarming ( OR=15.249, 95% CI: 1.357 to 279.571, P=0.038) were independent risk factors for the appearance of premature ventricular contractions in the early postoperative period. Conclusions:The technique of total thoracoscopic surgery under induced moderate hypothermic ventricular fibrillation with cardiopulmonary bypass could be applied to repeated mitral valve surgeries with less trauma and faster recovery. Persistent preoperative atrial fibrillation and excessive rewarming are independent risk factors for the occurrence of premature ventricular contractions in the early postoperative period.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

OBJECTIVE: The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain (RBD) recombinant protein formulated with CpG 1826 plus alum dual adjuvant. METHODS: The BA.2 variant RBD (residues 308-548) fusing TT-P ₂ epitope was obtained from prokaryotic expression system, purification technology and dialysis renaturation, which was designated as Sot protein. The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval (day 0 and 14). On day 28, the number of effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were determined by enzyme-linked immunospot (ELISpot) assay. The serum IgG, IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay (ELISA). In addition, the level of neutralizing antibodies (NAbs) induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay. RESULTS: The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression, protein purification and dialysis renaturation. The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs, which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants. Meanwhile, Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ (635.00 ± 17.62) and IL-4 (279.20 ± 13.10), respectively. Combined with a decreased IgG1/IgG2a ratio in the serum, which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response. CONCLUSION The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity, which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.
Animals ; COVID-19 Vaccines/immunology* ; Alum Compounds/pharmacology* ; Mice, Inbred BALB C ; Vaccines, Subunit/immunology* ; Mice ; SARS-CoV-2/immunology* ; Oligodeoxyribonucleotides/administration & dosage* ; Female ; Adjuvants, Immunologic ; COVID-19/immunology* ; Antibodies, Viral/blood* ; Immunogenicity, Vaccine ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/blood* ; Adjuvants, Vaccine ; Immunoglobulin G/blood*

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1β and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1β in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.
Animals ; Rats ; Chondrocytes ; NF-kappa B ; Iodoacetic Acid ; Inflammation ; MAP Kinase Signaling System ; Apoptosis