Resistance to poly adenosine diphosphate (ADP)-ribose polymerase inhibitor (PARPi) presents a considerable obstacle in the treatment of ovarian cancer. F-box and tryptophan-aspartic (WD) repeat domain containing 11 (FBXW11) modulates the ubiquitination of growth-and invasion-related factors in lung cancer, colorectal cancer, and osteosarcoma. The function of FBXW11 in PARPi therapy is still ambiguous. In this study, RNA sequencing (RNA-seq) showed that FBXW11 expression was raised in ovarian cancer cells that had been treated with PARPi. FBXW11 was abnormally expressed at low levels in high-grade serous ovarian cancer (HGSOC) tissues, and low levels of FBXW11 were associated with shorter overall survival (OS) and progression-free survival (PFS) in HGSOC patients. Overexpressing FBXW11 made ovarian cancer more sensitive to PARPi, while knocking down FBXW11 made it less sensitive. The four-dimensional (4D) label-free quantitative proteomic analysis revealed that FBXW11 targeted S100 calcium binding protein A11 (S100A11) and promoted its degradation through ubiquitination. The increased degradation of S100A11 led to less efficient DNA damage repair, which in turn contributed to increased PARPi-induced DNA damage. The role of FBXW11 in promoting PARPi sensitivity was also confirmed in xenograft mouse models. In summary, our study confirms that FBXW11 promotes the susceptibility of ovarian cancer cells to PARPi via affecting S100A11-mediated DNA damage repair.

Radiopharmaceuticals operate by combining radionuclides with carriers. The radiation energy emitted by radionuclides is utilized to selectively irradiate diseased tissues while minimizing damage to healthy tissues. In comparison to external beam radiation therapy, radionuclide drugs demonstrate research potential due to their biological targeting capabilities and reduced normal tissue toxicity. This article reviews the applications and research progress of radiopharmaceuticals in cancer treatment. Several key radionuclides are examined, including ²²³Ra, ⁹⁰Y, Lutetium-177 (¹⁷⁷Lu), ²¹²Pb, and Actinium-225 (²²⁵Ac). It also explores the current development trends of radiopharmaceuticals, encompassing the introduction of novel radionuclides, advancements in imaging technologies, integrated diagnosis and treatment approaches, and equipment-medication combinations. We review the progress in the development of new treatments, such as neutron capture therapy, proton therapy, and heavy ion therapy. Furthermore, we examine the challenges and breakthroughs associated with the clinical translation of radiopharmaceuticals and provide recommendations for the research and development of novel radionuclide drugs.
Humans ; Radiopharmaceuticals/therapeutic use* ; Neoplasms/radiotherapy* ; Radioisotopes/therapeutic use* ; Animals

Tripterygium wilfordii is widely used in the treatment of autoimmune system diseases, but its obvious reproductive toxicity limits the clinical application and promotion of the drug. At present, there is no clear solution to the reproductive injury of Tripterygium wilfordii. TCM believes that its reproductive toxicity lies in its properties of pungent, bitter, and cold. Long-term use can dry liver and blood, hurt liver and yang, consume kidney essence, damage kidney and yang, destroy the balance of qi and blood, yin and yang in the internal organs, and cause infertility. Based on the relationship between liver and kidney and human reproductive function, this article proposed to understand the reproductive toxicity of Tripterygium wilfordii from the perspective of "Yi and Gui homology", and explored the method of reducing the reproductive toxicity of Tripterygium wilfordii according to the thought of "treating liver and kidney together", in order to expand the theoretical thinking of TCM for the safe clinical application of this drug.

Diabetic peripheral neuropathy (DPN) is the common chronic complication of diabetes, which can lead to foot ulcers, gangrene, and amputation in severe cases, seriously affecting their quality of life. DPN belongs to the category of "arthralgia", "hemorrhoids" and other categories of TCM, and the main pathogenesis is the deficiency of qi and blood, yin and yang, and the obstruction of the meridians by phlegm and stasis. Clinically, DPN is more common with qi deficiency and blood stasis syndrome. Based on the theory of "qi meridian constant communication" in the Huang Di Nei Jing, this article proposed that for patients with DPN with qi deficiency and blood stasis syndrome, the treatment should be based on the principle of "invigorating qi and activating blood circulation, dissolving stasis and arthralgia", so that the patients' qi meridian can be accessible, delay the disease progression, and provide reference for the TCM treatment of DPN.

Objective: To understand the current situation and differences in physical activity among children and adolescents in different regions of China, so as to provide a scientific reference for promoting the level of overall physical activity promotion among children and adolescents in China. Methods: From June to December 2023, the student satisfaction assessment questionnaire for the national children and adolescents theme fitness activity "Run, Youth!" was conducted, which was administered via a combined online and offline questionnaire survey to explore 397 013 students participation in the "Run, Youth!" activity in 2023. Descriptive statistics, Logistic regression, and other approaches were utilized for data analysis. Results: There were notable disparities in the rates of children and adolescents meeting the physical activity standards among northeast China, northwest China, north China, east China, central China and southwest China (10.27%, 11.79%, 9.32%, 8.48%, 8.81%, 7.30%) ( χ 2=33.48, P <0.05). The results of multivariate Logistic regression analysis showed that rate of recommended level of physical activity among children in northwest China, boys, children aged 16-18, children in urban areas were relatively high ( OR =1.12, 1.68, 0.60, 1.88, P < 0.05 ). After adjusting for confounding factors, the results of binary Logistic regression analysis showed that there was an interactive effect relationship between the interaction of region, age, gender, and urban-rural distribution and physical activity among children and adolescents ( OR=0.51, P <0.01). Based on gender analysis, weekly physical activity duration of boys in each region surpassed that of girls; based on age analysis, except for the central and southwestern regions, weekly physical activity duration of children and adolescents gradually increased with age in other regions; based on the proportion of urban and rural areas, weekly physical activity duration of children and adolescents in urban areas across all regions exceeded that in rural areas. Conclusions The attainment rate of sufficient physical activity among children and adolescents in northwest China is the highest, and the differences between regions are not significant. The participation and level of physical activity of male students in each region surpass those of females and the attainment rate of physical activity of physical activity of urban children and adolescents is higher than that of those in rural areas.

The research focus of diabetes, a common chronic metabolic disease, has shifted from individual factors to environmental factors at the population level. Epidemiological studies suggest an association between exposure to environmental pollutants and the risk of diabetes. Major environmental pollutants include organochlorine pesticides, polychlorinated biphenyls, phthalates and their metabolites, and arsenics, which primarily enter the human body through the skin, respiratory tract, and digestive system. Long-term exposure to these pollutants can affect the pathology of diabetes through various mechanisms, such as promoting insulin resistance, causing insulin secretion deficiencies, inducing oxidative stress-induced glucose metabolism disorders, and affecting DNA methylation. However, the potential damaging mechanism of the impact of environmental pollutants on diabetes remain unclear. Limitations such as insufficient sample sizes, uncertainties regarding exposure time and dosage, and differences between single and co-exposures. In the future, it is necessary to focus on exploring and analyzing the mechanisms of environmental pollutant exposure on diabetes to develop effective prevention strategies, control and reduce the incidence and development of diabetes, and provide new insights into its diagnosis and treatment.

ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ²=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.

随着铜绿假单胞菌（铜绿）的耐药性逐年增强，铜绿感染已经成为公共医疗卫生的重点关注问题。线粒体自噬及其介导的线粒体功能障碍在多种细菌感染中已被报道，但线粒体功能障碍在宿主调控铜绿感染中的作用尚不明确。因此，本研究建立铜绿刺激小鼠巨噬细胞感染模型和小鼠急性铜绿感染模型，探讨铜绿是否通过诱导线粒体自噬改变线粒体功能，进而影响宿主免疫炎症反应和细胞毒性，并通过监测生存率和肺组织病理学变化进一步确定线粒体自噬在小鼠铜绿体内感染模型中的作用。结果表明，铜绿引起小鼠腹腔巨噬细胞线粒体功能障碍，并通过线粒体自噬途径清除铜绿刺激引起的活性氧（ROS）累积，从而抑制铜绿引起的促炎性细胞因子分泌并增强细胞毒性。体内实验进一步确认线粒体自噬在铜绿体内感染中的作用。
Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Pseudomonas aeruginosa ; Macrophages/metabolism* ; Mitochondria ; Cytokines/metabolism*

Objective:To study the features of adenomyomatous hyperplasia (AH) of the Vaterian system (common bile duct and ampulla of Vater) to help in the diagnosis and management of this disease.Methods:A retrospective analysis on the data of 17 patients who had a postoperative pathological diagnosis of AH of the Vaterian system treated from January 2005 to December 2021 at the First Medical Center of the PLA General Hospital was carried out with 12 males and 5 females, aged (58.4±11.3) years. The clinical presentations, treatment and postoperative pathology of these patients were analyzed. Patients with dysplasia of the tubular mucosal epithelium in the non-cancerous area around the AH under microscopy were included in the AH with dysplasia group ( n=8), and those without dysplasia were included in the control group ( n=9). The clinical characteristics of the two groups were compared. Results:The main clinical symptoms were abdominal pain in 8 patients, jaundice in 7 patients and fever in 2 patients. Preoperative imaging showed 10 cases of occupying lesions and 6 cases of abnormally dilated intrahepatic and extrahepatic bile ducts without obvious lesions or stones or biliary tract injury stenosis. Sixteen patients underwent radical pancreaticoduodenectomy, and 1 patient underwent extrahepatic biliary resection combined with choledochojejunostomy for bile duct obstruction due to biliary stones, 3 patients had combined malignant tumors, 1 patient had a carcinoma of AH origin at the ampulla of Vater, and the other 2 patients had neoplastic lesions in the mucosal epithelium adjacent to the AH (cholangiocarcinoma and ampullary carcinoma, respectively). There were no significant differences in age, gender, bile duct stones, cholangitis, combined carcinoma and liver function indexes between the two groups of patients with AH of the Vaterian system (all P>0.05). Conclusion:Adenomyomatous hyperplasia of the Vaterian system was difficult to distinguish preoperatively from malignant tumors basing on its clinical presentations or imaging findings. Such patients are recommended to be treated surgically.

Objective To explore the classification and characteristics of common syndromes of primary liver cancer and provide reference for clinical treatment.Methods Collect the four diagnostic information of patients with primary liver cancer from two top three TCM hospitals in Henan Province,and build a database.Using Lantern 5.0 software,based on two-step hidden tree analysis,a hidden structure model was constructed,and common syndromes of primary liver cancer were extracted through comprehensive clustering.SPSS 23.0 software was used for factor analysis and systematic cluster analysis to infer the potential syndromes.Combined with the results of different methods and professional knowledge,the syndrome classification of primary liver cancer was determined.Results A total of 1353 patients with 105 symptoms of primary liver cancer were included.59 symptoms with an analysis frequency≥40 were included to construct a hidden structure model,24 hidden variables were obtained,and 5 common syndromes were obtained by comprehensive clustering,namely,qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,liver and gallbladder damp heat syndrome.20 common factors were obtained by factor analysis for symptoms with frequency>3%,and 8 common syndromes were inferred by cluster analysis with common factors.7 common syndromes and characteristics were finally determined by combining different methods and expertise.Conclusion The common syndromes of primary liver cancer are qi deficiency syndrome,liver depression and qi stagnation syndrome,blood stasis syndrome,water dampness stagnation syndrome,yin deficiency syndrome,liver and gallbladder damp heat syndrome,spleen deficiency and dampness stagnation syndrome.The results objectively reflect the actual situation of patients with primary liver cancer,and can provide reference for the treatment of primary liver cancer based on syndrome differentiation.