Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To assess the levels and abnormal rates of trace elements and vitamins among older patients in Beijing Hospital, and to analyze the correlations between these measured indicators.Methods:This study selected 49 older individuals who underwent physical examinations at Beijing Hospital between May 2021 and March 2024.The participants were divided into two age groups: 60-79 years old(23 cases)and 80-100 years old(26 cases). Levels' differences of trace elements and vitamins between the two age groups were analyzed.Pearson correlation analysis was used to investigate the correlations among the tested indicators, and multivariate analysis was conducted using a generalized linear regression model.Results:Among the 49 older individuals, the overall abnormal rate for trace element test results was 8.16%(4 cases), with 2 cases of iron(Fe)deficiency(4.08%)and 2 cases of calcium(Ca)deficiency(4.08%). The overall abnormal rate for vitamin test results was 24.49%(12 cases), which included 5 cases of vitamin B2 deficiency(10.20%), 1 case of vitamin C deficiency(2.04%), and 6 cases of vitamin D deficiency(12.24%). Statistically significant differences were observed between the two age groups in zinc(Zn)and vitamin C levels( t=2.84, 2.83; P=0.007, 0.007). Pearson correlation analysis revealed correlations among 19 pairs of indicators.The top five correlations were between plumbum(Pb)and cadmium(Cd)( r=0.769, P<0.001), Fe and manganese(Mn)( r=0.685, P<0.001), Ca and magnesium(Mg)( r=0.677, P<0.001), vitamin B12 and vitamin C( r=0.455, P=0.001), and vitamin B9 and vitamin D( r=0.422, P=0.003), respectively.The results of the multivariate analysis indicated that, after adjusting for the effects of age group and gender, statistical differences in correlations remained among the remaining trace elements and vitamins, except for those between vitamin B1 and vitamin B12, vitamin B1 and vitamin C, and vitamin A and vitamin D (all P<0.05). Conclusions:The deficiency rates of trace elements and vitamins remain notably high among older patients in our hospital, underscoring the necessity for enhanced nutritional supplementation and regular monitoring of trace element and vitamin levels within this population.Furthermore, a correlation exists between trace elements and vitamins, which offers valuable insights for the diagnosis and treatment of related diseases.

Objective To understand the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) in medical staff in Beijing City. Methods A total of 2 687 medical staff were selected as the research subjects using the multi-stage sampling method. The current situation of WMSDs and occupational stress, anxiety symptoms, depressive symptoms, and insomnia symptoms were investigated using the Musculoskeletal Disorders Questionnaire, the Core Occupational Stress Scale, the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire Depression Scale, and the Self-Sleep Management Questionnaire. The Max-Min Hill-Climbing algorithm was used to construct a Bayesian network model to analyze the influencing factors and internal relationships of WMSDs and to conduct reasoning and prediction of the model. Results The prevalence of WMSDs among the research subjects was 88.9%. Binary logistic regression analysis was used to identify age, educational level, personal monthly income, anxiety symptoms, depressive symptoms, insomnia symptoms, prolonged forward-head desk work, and prolonged static posture work to construct the Bayesian network model. The model consisted of nine nodes and eleven directed edges. Prolonged static posture work, prolonged forward-head desk work, and anxiety symptoms were directly related to WMSDs. Age and educational level were indirectly related to WMSDs through their influence on prolonged forward-head desk work. Depression symptoms were indirectly associated with WMSDs through their influence on anxiety symptoms. The model's prediction accuracy was 90.5%. Conclusion The prevalence of WMSDs among medical staff in Beijing City is relatively high. Prolonged static posture work, prolonged forward-head desk work, and anxiety symptoms may directly increase the risk of developing WMSDs.

Objective To explore the application of case-based learning(CBL)approach in the basic medical stage for eight-year clinical medical program.Methods A total of 320 students from the eight-year clinical medicine pro-gram at Peking Union Medical College in the grades of 2014-2015 and 2019-2020 were selected as the study subjects.These students were divided into two groups,162 students in the classes of 2014 and 2015 as the control group,and 158 students in the classes of 2019 and 2020 as the experimental group.The students in the control group received classic teaching in the basic medicine stage characterized by traditional lectures as the main teaching method.The students in the experimental group received traditional lectures supplemented by CBL.In this study,the cardiovascular system was taken as an example,and the assessment scores and questionnaires of the two groups of students were collected in order to evaluate the teaching effectiveness and to obtain timely teaching feedback.Results Traditional lecture combined with CBL method significantly improved the theory assessment scores of students in the experimental group,stimulated learning interest and intrinsic motivation,and enhanced team learn-ing and problem-solving ability.Students believed that CBL teaching could effectively improve the ability to link theory to clinical practice.In addition,CBL teaching method encouraged the interaction between teachers and students and improved teaching efficiency.Conclusions Well-designing and well-organized CBL teaching from multiple levels,including teachers,students,and curricula,can be better accepted and acknowledged by students from eight-year clinical medical program at the stage of basic medical education.

Objective:To assess the levels and abnormal rates of trace elements and vitamins among older patients in Beijing Hospital, and to analyze the correlations between these measured indicators.Methods:This study selected 49 older individuals who underwent physical examinations at Beijing Hospital between May 2021 and March 2024.The participants were divided into two age groups: 60-79 years old(23 cases)and 80-100 years old(26 cases). Levels' differences of trace elements and vitamins between the two age groups were analyzed.Pearson correlation analysis was used to investigate the correlations among the tested indicators, and multivariate analysis was conducted using a generalized linear regression model.Results:Among the 49 older individuals, the overall abnormal rate for trace element test results was 8.16%(4 cases), with 2 cases of iron(Fe)deficiency(4.08%)and 2 cases of calcium(Ca)deficiency(4.08%). The overall abnormal rate for vitamin test results was 24.49%(12 cases), which included 5 cases of vitamin B2 deficiency(10.20%), 1 case of vitamin C deficiency(2.04%), and 6 cases of vitamin D deficiency(12.24%). Statistically significant differences were observed between the two age groups in zinc(Zn)and vitamin C levels( t=2.84, 2.83; P=0.007, 0.007). Pearson correlation analysis revealed correlations among 19 pairs of indicators.The top five correlations were between plumbum(Pb)and cadmium(Cd)( r=0.769, P<0.001), Fe and manganese(Mn)( r=0.685, P<0.001), Ca and magnesium(Mg)( r=0.677, P<0.001), vitamin B12 and vitamin C( r=0.455, P=0.001), and vitamin B9 and vitamin D( r=0.422, P=0.003), respectively.The results of the multivariate analysis indicated that, after adjusting for the effects of age group and gender, statistical differences in correlations remained among the remaining trace elements and vitamins, except for those between vitamin B1 and vitamin B12, vitamin B1 and vitamin C, and vitamin A and vitamin D (all P<0.05). Conclusions:The deficiency rates of trace elements and vitamins remain notably high among older patients in our hospital, underscoring the necessity for enhanced nutritional supplementation and regular monitoring of trace element and vitamin levels within this population.Furthermore, a correlation exists between trace elements and vitamins, which offers valuable insights for the diagnosis and treatment of related diseases.

Circuating tumor cells (CTC) are cells that are shed from the primary sites of malignancies and enter the bloodstream through the blood vessel or lymphatic system. The formation of CTC is a key step in the tumor metastasis process. CTC can reflect the heterogeneity of solid tumors in time and space, and can be used as an important supplementary method for pathological diagnosis, prognostic interpretation, disease detection and molecular typing. Some researchers also apply CTC to carry out culture in vitro, functional detection and histochemical analysis. This article reviews the recent research of CTC in diagnosis and assessment of efficacy, prognosis and metastasis of breast cancer.

Objective To investigate the regulation of naringin on apoptosis of airway inflammatory cells in asthmatic mice and its relationship with Tas2rs.Methods 36 BALB/c mice were randomly divided into 6 groups(n=6):blank control group,ovalbumin model group(OVA),dexamethasone group(10 mg·kg-1,positive control drug),naringin low,medium and high dose groups(10,20,40 mg·kg-1).Airway asthma was induced by OVA in all groups except the blank control group.After continuous administration of solvent,dexamethasone or naringin for 6 days,the respiratory function and the number of cells in alveolar lavage fluid of mice were measured,the lung and airway morphology of mice were observed,respiratory resistance(Rrs),lung elastic resistance(Ers)and respiratory compliance(Crs)were measured,and mRNA expression levels of lung tissue-related pro-apoptotic factors were measured.The mRNA expression levels of Tas2rs and its downstream genes were determined.Results Compared with OVA model group,naringin could dose-dependent decrease Rrs and Ers,increase Crs,and decrease the number of leukocytes,eosinophils,lymphocytes and neutrophils.Compared with OVA model group,the infiltration of inflammatory cells in lung tissue was significantly reduced in high-dose naringin group,and the mRNA expression levels of Tas2r108,Tas2r135,Tas2r143 and their downstream target genes α-gust and Trpm5 in lung and airway tissue were significantly decreased.The mRNA expression levels of proapoptotic factors P53,Bax and Casp3 were increased,while the mRNA expression levels of apoptosis inhibitor Bcl2 were decreased.Conclusion Naringin prophylactic administration can promote the activation of airway Tas2rs signal,decrease the number of airway inflammatory cells and alleviate airway injury in asthmatic mice.Naringin as a Tas2rs agonist can be developed as a potential anti-asthmatic agent.

Background There are a variety of microorganisms in ambient air, and susceptible people can be infected once contact with pathogenic microorganisms in the environment. In order to avoid the spread of pathogenic bacteria, disinfection is the simplest and most effective way of killing pathogenic bacteria in the environment to block the contact between pathogenic bacteria and humans. Sodium hypochlorite (NaClO) is the most widely used disinfectant, but its safety in ambient air disinfection is not clear yet. Objective To establish a model of bronchial epithelial cell (BEAS-2B) injury induced by NaClO, and to explore the mechanism of the toxic effect of NaClO disinfectants on BEAS-2B. Methods Cells were treated with concentration gradients of 0, 25, 50,100, 200, and 400 μmol·L⁻¹ of the diluted NaClO (100 mmol·L⁻¹) standard solution, respectively, and cell activity was measured by cell counting kit-8 (CCK-8) assay after 15 and 30 min. Cells treated with 0, 25, and 50 μmol·L⁻¹ NaClO were selected to observe the cell morphology under an inverted microscope, apoptosis was determined by flow cytometry Annexin V FITC / PI double staining to determine the final experimental concentration. The morphology of organelles such as mitochondria was observed under a transmission electron microscope. Mitochondrial membrane potential of the cells was detected by JC-1 staining. Intracellular Ca²⁺ concentration was measured with a Fluo-4 AM fluorescent probe. Total cellular reactive oxygen species (ROS) was detected with a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probe, cell mitochondrial ROS with a dihydroethidium (DHE) fluorescent probe, and lipid peroxidation intermediate malondialdehyde (MDA) with a commercial kit. Results Compared with 0 μmol·L⁻¹, NaClO treatment group, cell morphology did not change a lot after 25 μmol·L⁻¹ NaClO treatment for 30 min, and the cells began to wrinkle and become round after 30 min treatment with 50 μmol·L⁻¹ NaClO, showing about 70% of normal cell viability (P<0.01). So 30 min 50 μmol·L⁻¹ NaClO treatment was selected for the subsequent experiment. The experimental results found that compared with the 0 μmol·L⁻¹ NaClO treatment group, the number of apoptotic cells increased (P<0.05), the mitochondrial membrane potential decreased (P<0.01), the intracellular Ca²⁺ concentration increased (P<0.05), the cellular ROS level increased (P<0.05), the mitochondrial ROS level increased (P<0.01), and the MDA content increased (P<0.01) in the NaClO treatment group.. Conclusion The study has successfully established a model of BEAS-2B injury induced by NaClO, and found that NaClO can lead to cell damage by inducing apoptosis and oxidative stress in BEAS-2B cells. According to the results, there are two possible reasons. First, NaClO solves in water to form hypochlorous acid (HClO) which is oxidative and increases the intracellular ROS level after entering cells, leading to cellular oxidative stress. Second, HClO enters cells to directly attack the mitochondrial membrane, resulting in the imbalance of potential inside and outside the mitochondrial membrane, and apoptosis caused by Ca²⁺ efflux.

Objective To investigate the effect of thalidomide combined with infliximab (IFX) in treatment of refractory inflammatory bowel disease (IBD) and its effects on insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). Methods A total of 120 patients with refractory IBD were randomly divided into experimental group and control group, with 60 cases in each group. The two groups were given conventional treatment (mesalazine), the control group was given IFX, and the experimental group was given IFX combined with thalidomide, continuous treatment for two months. The efficacy, intestinal flora disturbance rate, adverse reactions, Crohn's disease activity index (CDAI), Lewis score, serum IGF-1, TGF-β1 levels and nutritional status indexes[albumin (ALB), transferrin (Tf)]before and after treatment for 1 month and 2 months of the two groups were compared. Results The total effective rate of the experimental group was significantly higher than that of the control group (P < 0.05). After one month and two months of treatment, CDAI and Lewis scores of the experimental group were significantly lower than those of the control group (P < 0.05); the serum levels of IGF-1, TGF-β1 as well as ALB and Tf in the experimental group were significantly higher than those in the control group (P < 0.05). The improvement of intestinal flora disturbance rate in the experimental group was significantly better than that in the control group (P < 0.05). There was no significant difference in the incidence of oral and nasal mucosa dryness, throat discomfort, nausea and vomiting between two groups (P>0.05). Conclusion In the treatment of refractory IBD patients, thalidomide combined with IFX can regulate serum IGF-1 and TGF-β1 levels, effectively relieve clinical manifestations, inhibit inflammatory activities, and improve nutritional status and intestinal flora disorders of patients, and it has high safety.

ObjectiveTo understand the current situation and influencing factors of health service demands of new residents in Shanghai. MethodsFrom July to August 2020， a questionnaire survey was conducted in 1 358 new residents from 36 survey points in 7 districts of the city. The questionnaire included the basic medical insurance coverage in the inflow area， the current situation of medical demand and related influencing factors， and the demands for other health services. Results47.1%（562/1 194）of new residents did not choose to seek timely medical treatment when they were not feeling well. The main reason was that the working hours occupied the medical treatment time. Logistic regression analysis showed that the main factors affecting the medical needs in new residents were the average daily working hours， living area and type of residence， health status， physical examination and physical exercise， and the type of basic medical insurance. The demands of new residents for "health consultation of common diseases and frequently occurring diseases"， "health behavior intervention （such as smoking cessation and alcohol restriction）"， "medical guidance and publicity"， "accidental injury prevention （traffic， work， falling， etc.）" and "maintenance of legitimate rights and interests of health" were 57.1%（682/1 194）、41.3%（493/1 194）、34.9%（417/1 194）、32.2%（385/1 194） and 31.9%（381/1 194）， respectively. ConclusionNew residents demands for medical services cannot be met. We should actively improve the working and living conditions of new residents， improve the construction of new residents' health service system， and improve the utilization level of health services.