ObjectiveTo prepare a recombinant PETase with a dual-catalytic-triad and to evaluate its efficiency in the biodegradation of polyethylene terephthalate （PET）. MethodsBased on the crystal structure of wild-type PETase， point mutations （T88H/L117D） were introduced via site-directed mutagenesis. The recombinant protein was prepared using prokaryotic expression and chromatography purification techniques. The enzymatic hydrolysis of the mutant PETase was assessed by relatively quantifying the products mono （2-hydroxyethyl） terephthalate （MHET） and terephthalic acid （TPA）. ResultsBoth wild-type and mutant PETases accumulated as inclusion bodies， accounting for approximately 20% of the total bacterial protein. After solubilization in urea， the proteins were eluted at 300 mmol/L imidazole during affinity chromatography purification， with concentrations of 1.824 and 1.833 mg/mL and purities of 83.11% and 84.32%， respectively. Subsequent anion-exchange chromatography yielded highly pure enzymes in the 200 mmol/L NaCl fraction： 2.776 mg/mL （96.86% purity） for the wild type and 1.967 mg/mL （95.13% purity） for the mutant. Following refolding， the final concentrations were 0.484 mg/mL for the wild type and 0.991 mg/mL for the mutant. Hydrolysis assays revealed that the mutant released MHET and TPA at （237.67±17.00）% and （197.33±12.01）% of the wild-type levels， respectively. ConclusionThe T88H/L117D dual-catalytic-triad PETase is successfully prepared and it significantly enhanced PET-degrading activity， thus， it′s a promising biocatalyst for PET bioremediation.

Objective To explore the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal tumors. Methods A retrospective analysis was conducted on the clinical data of 17 patients who underwent transesophageal endoscopic resection for benign mediastinal tumors at the Endoscopy Center of Zhongshan Hospital, Fudan University, between January 1, 2016 and December 31, 2024. Epidemiological characteristics, surgical parameters, adverse events, and follow-up outcomes were analyzed. Results Among the 17 patients, there were 9 males and 8 females, with an average age of (42.4±14.5) years and an average tumor size of (2.6±1.6) cm. Pathological types included esophageal duplication cysts (6 cases, 35.3%), bronchogenic cysts (5 cases, 29.4%), gastroenteric cysts (3 cases, 17.6%), schwannomas (2 cases, 11.8%), and lymphangioma (1 case, 5.9%). Fourteen patients (82.4%) underwent submucosal tunneling endoscopic resection (STER), 3 patients (17.6%) underwent natural orifice transluminal endoscopic mediastinal surgery. All surgeries were successfully completed without conversion to open surgery. En bloc resection was achieved in 11 patients (64.7%), with an average operative time of (60.9±32.6) min. No intraoperative bleeding or mucosal injury occurred, and 4 patients (23.5%) experienced minor complications (pneumothorax, fever, recurrent laryngeal nerve injury), all of which resolved with conservative treatment. The average postoperative hospital stay was (3.2±1.5) days, and no recurrence was observed during the follow-up period. Conclusions Transesophageal endoscopic resection of benign mediastinal tumors is a safe, effective, and minimally invasive treatment method. Further validation of its efficacy and safety through large-scale prospective studies is warranted.

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 investigate the epidemic characteristics of imported malaria in Dezhou City, Shandong Province.Methods:The epidemic data of imported malaria in Dezhou City from January 2014 to December 2024 reported by the China Disease Prevention and Control Information System and the Parasitic Disease Prevention and Control Information Management System were collected, and the sources of infection and epidemiological characteristics of the cases were analyzed. Meanwhile, the surveillance data of malaria vector populations in Dezhou City reported by the China Disease Control and Prevention Information System during the same period were collected, and the types of mosquito populations were analyzed.Results:From 2014 to 2024, a total of 100 cases of imported malaria were reported in Dezhou City, all of which were laboratory-confirmed cases, mainly falciparum malaria, accounting for 61.0% (61/100). The cases came from 21 countries, mainly imported from Africa, accounting for 99.0% (99/100). The cases were mainly male, accounting for 99.0% (99/100). The age range was mainly between 21 and 50 years old, accounting for 88.0% (88/100). The occupations were mainly construction industry workers and catering industry personnel, accounting for 41.0% (41/100) and 27.0% (27/100), respectively. The median time interval between the entry of the case and the onset of the disease was 8 days, and the median time interval between the onset of the disease and diagnosis was 6 days. From 2014 to 2024, a total of 16 803 mosquitoes were captured in Dezhou City, with the dominant mosquito species being Culex pipiens pallens, accounting for 89.1% (14 979/16 803). Conclusion:The imported malaria in Dezhou City is mainly falciparum malaria imported from Africa, and the cases are mainly male, young and middle-aged people and construction industry workers.

Objective:To investigate the epidemic characteristics of imported malaria in Dezhou City, Shandong Province.Methods:The epidemic data of imported malaria in Dezhou City from January 2014 to December 2024 reported by the China Disease Prevention and Control Information System and the Parasitic Disease Prevention and Control Information Management System were collected, and the sources of infection and epidemiological characteristics of the cases were analyzed. Meanwhile, the surveillance data of malaria vector populations in Dezhou City reported by the China Disease Control and Prevention Information System during the same period were collected, and the types of mosquito populations were analyzed.Results:From 2014 to 2024, a total of 100 cases of imported malaria were reported in Dezhou City, all of which were laboratory-confirmed cases, mainly falciparum malaria, accounting for 61.0% (61/100). The cases came from 21 countries, mainly imported from Africa, accounting for 99.0% (99/100). The cases were mainly male, accounting for 99.0% (99/100). The age range was mainly between 21 and 50 years old, accounting for 88.0% (88/100). The occupations were mainly construction industry workers and catering industry personnel, accounting for 41.0% (41/100) and 27.0% (27/100), respectively. The median time interval between the entry of the case and the onset of the disease was 8 days, and the median time interval between the onset of the disease and diagnosis was 6 days. From 2014 to 2024, a total of 16 803 mosquitoes were captured in Dezhou City, with the dominant mosquito species being Culex pipiens pallens, accounting for 89.1% (14 979/16 803). Conclusion:The imported malaria in Dezhou City is mainly falciparum malaria imported from Africa, and the cases are mainly male, young and middle-aged people and construction industry workers.

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.

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.

Diabetes, hypertension, and dyslipidemia, collectively referred to the " Three Highs, " represent increasingly prevalent metabolic risk factors in China. Many individuals experience all three conditions concurrently, significantly heightening the risk of cardiovascular disease and mortality. Although the National Metabolic Management Center(MMC) has been established for over eight years and has its unique features, the awareness, treatment, and control rates of these diseases in China remain low, and the efficiency of community management is insufficient. According to the previous two editions of management guidelines and the most recent domestic and international diagnostic and treatment guidelines, this paper conducts an in-depth analysis of the operational experience and management strategies of the MMC. Its aim is to improve the efficiency of grassroots MMC mode management for " Three Highs" patients and ensure that patients receive more standardized management.

Objective:To evaluate immunogenicity of receptor binding domain (RBD) subunit vaccine formulated with CpG 1826 adjuvant in mice.Methods:BALB/c mice were intramuscularly inoculated with two doses of RBD recombinant protein formulated with CpG 1826 adjuvant. The level of the specific IgG antibodies and neutralizing antibodies (NAbs) in serum were detected by ELISA and microneutralization assay, respectively. The effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were quantified by ELISpot.Results:RBD protein formulated with CpG 1826 adjuvant induced a high level of specific IgG antibodies (18 820.27) and NAbs, which had cross-neutralizing activity against SARS-CoV-2 prototype (776), BA.2 (676), and XBB.1.5 (97) variants. The specific effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were 382.4±16.1 and 180.6±4.78, respectively. Combined with an IgG1/IgG2a ratio (0.88) in serum, RBD protein formulated with CpG 1826 adjuvant induced Th1-type predominant immune response in mice.Conclusions:RBD subunit vaccine formulated with CpG 1826 adjuvant induced the strong cellular and humoral immune responses in mice, providing a scientific basis for the adjuvant application of SARS-CoV-2 subunit vaccines.