Tacrolimus is the cornerstone immunosuppressant after liver transplantation, effectively reducing the risk of post-operative rejection. However, optimizing its clinical dosage remains a major challenge. Cytochrome P450 (CYP) 3A5 is the principal enzyme governing tacrolimus metabolism and therefore dominates the metabolic process of the drug. CYP3A5 genetic polymorphisms are a key determinant of inter-patient variability of metabolic capacities and adverse clinical outcomes. In this article the population-specific distribution of CYP3A5 polymorphisms, the principal factors modulating early tacrolimus metabolism after liver transplantation and the clinical implementation of genotype-guided individualized dosing regimens were summarized. The aim is to provide a theoretical foundation for precise tacrolimus dosing strategies in liver transplantation, explore the feasibility of personalized medication approaches, and promote the practice of precision medicine in the field of organ transplantation.

Objective: To investigate the prevalence levels and trends of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023, so as to provide a basis for developing regional weight management strategies. Methods: Permanent residents aged ≥18 years from Zhejiang Province who participated in the China Chronic Disease and Risk Factor Surveillance Project in 2015, 2018, and 2023 were selected as survey subjects. Data on sociodemographic information, height, weight and waist circumference were collected through questionnaire surveys and physical examinations. The prevalence of overweight, obesity, and central obesity were calculated and standardized using data from the Seventh National Population Census of Zhejiang Province in 2020. The Cochran-Armitage trend test was employed to analyze the trends in prevalence of overweight, obesity, and central obesity across different genders, ages and regions. Results: A total of 23 902 individuals were surveyed, comprising 10 985 males (45.96%) and 12 917 females (54.04%). Participants were aged ≥60 years, with 13 088 individuals accounting for 54.76%. There were 9 388 urban residents (39.28%) and 14 514 rural residents (60.72%). The standardized prevalence of overweight among residents increased from 30.05% in 2015 to 33.98% in 2023, the standardized prevalence of obesity increased from 7.67% to 15.22%, and the standardized prevalence of central obesity increased from 22.81% to 33.82%, all showed upward trends (all P<0.05). In 2015, 2018, and 2023, the standardized prevalence of overweight was higher in males than in females. In 2018 and 2023, the standardized prevalence of obesity and central obesity were higher in males than in females (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both males and females showed upward trends (all P<0.05). In 2015, 2018 and 2023, the prevalence of central obesity showed an increasing trend with age (all P<0.05). From 2015 to 2023, upward trends were observed in the prevalence of overweight, obesity, and central obesity among residents aged 18-<45 years and aged ≥60 years, as well as in the prevalence of obesity and central obesity among residents aged 45-<60 years (all P<0.05). In 2015, 2018 and 2023, the standardized prevalence of overweight obesity were higher in urban areas than in rural areas, while the standardized prevalence of central obesity was lower in urban areas (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both urban and rural areas showed upward trends (all P<0.05). Conclusion From 2015 to 2023, the prevalence of overweight, obesity, and central obesity among adult residents in Zhejiang Province showed increasing trends, with variations in prevalence levels and trends observed across genders, ages, and urban / rural areas.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and biomedicine.In biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary surgery.For example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient education.Moreover,cancer models have been created using 3D printing technology for the research and selection of chemotherapy drugs.With the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

Objective To investigate the pathogenesis of superficial mycosis among naval trainees, and observe the efficacy of a novel antifungal drug. Methods A questionnaire survey was conducted on the onset, medication and recurrence of superficial fungal infection among the trainees from January, 2020 to July, 2020. At the same time, the new antifungal drug sulconazole nitrate spray was provided for treatment and the drug efficacy was observed. Results The participants generally lacked understanding and attention to superficial fungal infections. The incidence rate of superficial fungal infection was 52%, of which 76.2% of patients had recurrence of superficial fungal infection. The sulconazole nitrate spray showed great effect against these infections. Conclusion The trainees should understand the causes of superficial fungal infection through health education and seek medical treatment and medication in time. The cure rate of superficial fungal infections could only be improved through the collaborative management of the school, hospital, and trainees to reduce the impact of these infections on naval trainees’ work and life.

Macaque is a common animal model in drug safety assessment. Its behavior reflects its health condition before and after drug administration, which can effectively reveal the side effects of drugs. At present, researchers usually rely on artificial methods to observe the behavior of macaque, which cannot achieve uninterrupted 24-hour monitoring. Therefore, it is urgent to develop a system to realize 24-hour observation and recognition of macaque behavior. In order to solve this problem, this paper constructs a video dataset containing nine kinds of macaque behaviors (MBVD-9), and proposes a network called Transformer-augmented SlowFast for macaque behavior recognition (TAS-MBR) based on this dataset. Specifically, the TAS-MBR network converts the red, green and blue (RGB) color mode frame input by its fast branches into residual frames on the basis of SlowFast network and introduces the Transformer module after the convolution operation to obtain sports information more effectively. The results show that the average classification accuracy of TAS-MBR network for macaque behavior is 94.53%, which is significantly improved compared with the original SlowFast network, proving the effectiveness and superiority of the proposed method in macaque behavior recognition. This work provides a new idea for the continuous observation and recognition of the behavior of macaque, and lays the technical foundation for the calculation of monkey behaviors before and after medication in drug safety evaluation.
Animals ; Electric Power Supplies ; Macaca ; Recognition, Psychology

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Objective: To examine the correlation between frailty and lifestyle factors among middle-aged and elderly populations, so as to provide insights into the management of frailty among middle-aged and elderly populations. Methods : Middle-aged and elderly residents at ages of 45 ot 69 years were recruited using the convenient sampling method from seven townships in Changxing County of Zhejiang Province from 2019 to 2020. The demographic characteristics and lifestyle factors were collected using questionnaires, and the frailty was measured using the Chinese version of Tilburg Frailty Indicator ( TFI ). Factors affecting frailty were identified among middle-aged and elderly populations using the multivariable logistic regression model. Results: A total of 7 170 residents were surveyed, including 2 780 males ( 38.77% ) and 4 390 females ( 61.23% ), which had a median age of 56 (interquartile range, 10) years. The median frailty score was 2 (interquartile range, 3 ) among the study subjects, and the median frailty score was 2 ( interquartile range, 2 ) among residents at ages of 45 to 59 years, and 2 (interquartile range, 3) among residents at ages of 60 to 69 years. The overall detection of frailty was 16.07%, and the detection of frailty was 13.52% among subjects at ages of 45 to 59 years and 21.01% among subjects at ages of 60 to 69 years. Multivariable logistic regression analysis identified physical activity ( OR=0.826, 95%CI: 0.719-0.949 ) and sleep quality ( OR: 3.376-11.493, 95%CI: 2.907-15.808 ) as factors affecting frailty among middle-aged and elderly residents. Following age stratification, physical activity ( OR=0.817, 95%CI: 0.681-0.981 ) and sleep quality ( OR: 3.076-11.566, 95%CI: 2.518-18.216 ) as factors affecting frailty among subjects at ages of 45 to 59 years, while sleep quality ( OR: 3.777-11.827, 95%CI: 3.002-18.547 ) significantly correlated with frailty among residents at ages of 60 to 69 years. Conclusion Physical activity and sleep quality are associated with the risk of frailty among middle-aged and elderly populations.

In the process of radical resection of abdominal malignant tumors, large blood vessels are often invaded, which not only increases the difficulty of operation, but also directly affects the curative effect and prognosis. As the concept of expanded radical surgery combined with vascular resection and reconstruction and related techniques have been gradually recognized, surgeons have begun to use autologous, allogeneic or artificial vessels to repair the defective blood vessels during surgery, so as to achieve the effect of radical surgery. However, due to the short comings of these materials, scholars have been looking for better alternatives. In view of the fact that the mesothelial cells of the peritoneum and the endothelial cells of the blood vessels have many similarities in embryology, histology and physiology, and peritoneum is also easier to obtain than autologous, allogeneic or artificial vessels. To make the autologous peritoneum into a patch for repairing the defective blood vessels is feasible in theoretical and technical. In this paper, we review the current research progress of autologous peritoneal patch to repair blood vessels of defect.