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.

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*

OBJECTIVES: To compare the commonly used methods for analyzing treatment switching in clinical trials to facilitate selection of optimal methods in different scenarios. METHODS: Based on the data characteristics of patient conversion in oncology clinical trials, we simulated the survival time of patients across different scenarios and compared the bias, mean square error and coverages of the treatment effects derived from different methods. RESULTS: The sample size had an almost negligible impact on the outcomes of the various methods. Compared to conventional methods, more complex methods (RPSFTM, IPCW, TSE, and IPE) resulted in lower errors across different scenarios. The IPCW method could cause a significant increase in errors in cases where the probability of conversion was high. The TSE method had the lowest error and mean squared error when the risk was low and the probability of conversion was high. The IPE method had an obvious advantage in the scenario with a low probability of conversion, but it may slightly underestimate the treatment effect when the inflation factor was small. CONCLUSIONS The choice of a specific method for analyzing cohort transition should be made based on considerations of both the probability of conversion and inflation factor in different scenarios.
Humans ; Clinical Trials as Topic/methods* ; Neoplasms/therapy*

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.

The Department of Plastic and Reconstructive Surgery of the Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medical, has witnessed and propelled the remarkable evolution of China’s plastic and reconstructive surgery over the past sixty years. Established in 1961 under the leadership of its founding father, Professor Ti-sheng Chang, the department was built on the mission of "Preventing the injured from disabled, the disabled from incapable". It pioneered groundbreaking advancements in flap microsurgery, craniofacial surgery, and lymphatic medicine. Entering the 21st century, guided by its motto of "Openness, Innovation, Excellence, and Dedication", the department has developed a comprehensive, full-cycle diagnostic and treatment system covering all disease spectrums. With seven major specialties and 24 subspecialty divisions, it has achieved continuous breakthroughs in surface organ reconstruction, hemangioma and neurofibroma treatment, fat transplantation, and craniomaxillofacial surgery. These innovations have yielded landmark achievements, with multiple technologies receiving National Science and Technology Progress Awards, significantly advancing the field of reconstructive surgery in China. Committed to talent development, the department, as one of China’s first doctoral training centers and a national standardized training base for resident and specialist physicians, has trained over 750 postgraduate students, more than 240 resident and specialist trainees, and over 2 000 clinic fellow. It has also led the compilation of multiple national standardized textbooks in plastic surgery, making substantial contributions to professional education and training standardization. Through administration innovation, the department has established a "bed-bench-bed" closed-loop model, driving technological advancements and facilitating major translational achievements, including Class 1.1 new drugs and stem cell therapies. It pioneered a structured multi-site practice platform for surgeons, optimizing the allocation of medical resources. Now, the department is focusing on high-quality patient cohort and biobank development while exploring cutting-edge fields such as AI-assisted diagnostics, gene therapy, and brain-computer interfaces, striving to build a world-class discipline at the forefront of global reconstructive surgery.

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 observe the value of pituitary radiomics and MRI features combined model for predicting growth hormone(GH)status in pediatric short stature.Methods Totally 300 children with short stature were enrolled as training set,while other 73 cases were taken as external validation set.Based on growth hormone stimulation test,the children were divided into GH deficiency(GHD)group(n=228)and non-GHD group(n=145).The training set included 196 cases in GHD subgroup and 104 cases in non-GHD subgroup,while the validation set included 32 cases in GHD subgroup and 41 cases in non-GHD subgroup.Radiomics features of pituitary were extracted from T1WI.The key features were selected using least absolute shrinkage and selection operator(LASSO)regression,and machine learning models were subsequently constructed using support vector machine(SVM),logistic regression(LR),naive Bayes(NB)and K-nearest neighbor(KNN),respectively.Then combined models were constructed combining with MRI features,and the efficacy of each model was evaluated.Results The area under the curve(AUC)of SVM,LR,NB,and KNN radiomics model for predicting GH status in pediatric short stature was 0.860,0.831,0.838 and 0.901 in training set,0.788,0.829,0.823 and 0.770 in validation set,while of the relative combined SVM,LR,NB and KNN model was 0.924,0.903,0.859 and 0.920 in training set,and 0.827,0.881,0.836 and 0.718 in validation set.LRcombined model had the best overall performance,with sensitivity of 84.94％,specificity of 80.56％and accuracy of 83.61％in training set,and 80.95％,72.22％and 80.00％in validation set,respectively.Conclusion Pituitary radiomics and MRI features combined model could effectively predict GH status in pediatric short stature.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

This study aims to describe the population and regional distribution characteristics of smoking behavior among adult twins in the China Twin Registry (CNTR), as well as the concordance rates for smoking behavior in monozygotic and dizygotic twins, and estimate the heritability. The study population included adult twins in CNTR who had smoking questionnaire data. A random-effects regression model was used to describe the distribution of smoking behavior among different subgroups based on various characteristics. The concordance of smoking behavior between different zygosity groups was calculated, and heritability was estimated. A total of 28 444 twin pairs were included in this study, with an average age of (36.6±12.0) years. Among male twins, 41.2% were current smokers, while only 1.2% of females smoked. Higher smoking rates were observed among male smokers in the 50-59 age group ( z=23.0, P<0.001), northern regions ( z=2.9, P<0.01), rural areas ( z=-5.2, P<0.001), those who were divorced/widowed ( z=3.8, P<0.001), and first-born twins ( z=-4.3, P<0.001), while lower smoking rates were found in those with higher education ( z=-16.1, P<0.001) and unmarried individuals ( z=-16.0, P<0.001). The smoking concordance rate for male monozygotic twins was 69.6%, significantly higher than the 57.3% concordance rate for dizygotic twins ( χ 2=105.0, P<0.05). The heritability of smoking behavior in male twins was estimated at 28.9% (95% CI: 24.3%-33.4%). Stratified analyses showed differences in heritability across regions and age groups: the heritability in northern regions was 32.6% (95% CI: 27.3%-38.0%), higher than the 21.0% (95% CI: 12.4%-29.5%) observed in southern regions; the highest heritability of 35.1% (95% CI: 26.3%-43.9%) was found in the 18-29 age group, with heritability decreasing with age. In conclusion, the smoking rate and influencing factors in the twin population are similar to those in the general population, with unique characteristics, such as higher smoking rates in first-born twins. Genetic factors have a significant impact on smoking behavior.