ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L^-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L^-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L^-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

Epidemiology and medical statistics are essential courses for undergraduate students majoring in clinical medicine. By studying the two courses, they can obtain the core skills for their future clinical practice. High-level medical schools both at home and abroad have accumulated successful experiences in curriculum, teaching methods and teaching models of the two disciplines. These colleges have also carried out the exploration of the curriculum reform centering on "organ systems integration". This paper summarizes the current status of epidemiology and medical statistics teaching and curriculum integration in representative medical schools both at home and abroad, and puts forward suggestions for deepening teaching reform and optimizing the curriculum system to provide reference for the integration of epidemiology and medical statistics curriculums for undergraduate students majoring in clinical medicine in China.

Objective To explore the application effect of upper abdominal moxibustion combined with bedside ultrasound monitoring of gastric residual volume(GRV)in pre-pyloric feeding in stroke patients.Methods Eighty stroke patients admitted to the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital from January 1,to December 31,2023 were selected as the study subjects.They were divided into control group(n=38)and observation group(n=42)using a random number table method.All patients had a nasogastric tube for pre-pyloric feeding.The control group used the traditional syringe aspiration method to monitor GRV,while the observation group used upper abdominal moxibustion combined with bedside ultrasound to monitor GRV.The study compared the differences between two groups in terms of enteral nutrition intolerance,feeding complications,enteral nutrition compliance rate within 7 days of admission,time to achieve enteral nutrition compliance,and changes in hemoglobin(Hb),serum prealbumin,serum albumin(ALB),and serum transferrin before and after 14 days of feeding.Results The incidence rates of vomiting,abdominal distention,intra-abdominal hypertension,reflux,and aspiration pneumonia in observation group were lower than those in control group(P＜0.05).The rate of achieving intestinal nutrition standard within 7 days of hospitalization was significantly higher in observation group compared to the control group.The time to achieve intestinal nutrition standard was shorter in observation group compared to control group.Furthermore,after 14 days of feeding,the levels of Hb and ALB in observation group were higher than those in control group,and the differences were statistically significant(P＜0.05).Conclusion Upper abdominal moxibustion combined with bedside ultrasonic monitoring of GRV can significantly reduce intestinal nutrition intolerance and feeding complications during pre-pyloric feeding in stroke patients,shorten the time to achieve nutritional benchmarks,and improve nutritional status.

Per- and polyfluoroalkyl substances （PFASs） are a new type of persistent organic pollutants with global attention. They have shown multiple toxic effects due to their persistent accumulation in human body through exposure to environmental media such as drinking water， food， atmosphere， and soil. However， the bone toxicity of PFASs has not attracted enough attention. It is believed that the exposure and accumulation of PFASs in human have a significant impact on the bone health， especially hindering the healthy bone development in infants and adolescents， and aggravating the occurrence of bone loss and fracture in the elder populations. This paper will review the research progress of the effects of PFASs exposure on bone health indicators such as bone mineral density， and discuss the mechanisms of PFAS in bone toxicity. This review will provide references for revealing the effects of PFASs exposure on bone health and their toxic mechanisms.

ObjectiveTo establish an High Performance Liquid Chromatography-Inductively Coupled Plasma-Mass Spectrometry （HPLC-ICP-MS） method for determination of six arsenic species in human urine，including arseniccholine （AsC）， arsenobetaine （AsB）， arsenite （As³⁺）， dimethylarsinic acid （DMA⁵⁺）， monomethylarsonic acid （MMA⁵⁺）， and arsenate （As⁵⁺）. MethodsThe pH value of mobile phase and the content of anhydrous ethanol were optimized. Ammonium carbonate （50 mmol·L^-1， containing 2% anhydrous ethanol， pH-8.5） mobile phase was selected. Cl^- interference was eliminated by He mode. The arsenic species in 10-fold diluted human urine samples were separated by an Hamilton PRP X-100 anionic column. A method for the determination of six arsenic species was established. ResultsSix arsenic species could be separated in 13 minutes. The linear correlation coefficients were above 0.999. The limits of detection were 0.10‒0.20 μg·L^-1， and the limits of quantification were 0.30‒0.50 μg·L^-1. Precision experiments showed that RSD ranged from 5.96% to 9.07% when adding concentration 0.20 μg·L^-1； from 2.48% to 6.38% when adding concentration 2.00 μg·L^-1； and from 1.41% to 2.57% when adding concentration 5.00 μg·L^-1. Accuracy test showed that the recoveries were 80%‒125%. ConclusionThe established HPLC-ICP-MS method for determination of six arsenic species in human urine is rapid， accurate and sensitive. It can be applied to the determination of arsenic species in human urine.

Objective:To study the risk factors and prediction model of radiation pneumonitis (RP) after radical chemoradiotherapy for locally advanced esophageal cancer based on dosiomics.Methods:Clinical data of 105 patients with esophageal cancer undergoing radical chemoradiotherapy at Zhejiang Cancer Hospital between January 2020 and August 2021 were retrospectively analyzed. RP was scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Clinical factors, traditional dosimetric features and dosiomics features were collected, respectively. The features for predicting PR were analyzed by limma package. Support vector machine, k-nearest neighbor, decision tree, random forest and extreme gradient boosting were used to establish the prediction model, and the ten-fold cross-validation method was employed to evaluate the performance of the model. The differences of this model when different features were chosen were analyzed by delong test.Results:The incidence of RP in the whole group was 21.9%. One clinical factor, 6 traditional dosimetric features and 42 dosiomics features were significantly correlated with the occurrence of RP (all P<0.05). Support vector machine using linear kernel function yielded the optimal prediction performance, and the area under the receiver operating characteristic (ROC) without and with dosiomics features was 0.72 and 0.75, respectively. The models established by support vector machine, random forest and extreme gradient boosting were significantly different with and without dosiomics features (all P<0.05). Conclusion:The addition of dosiomics features can effectively improve the performance of the prediction model of RP after radiotherapy for esophageal cancer.

Objective To investigate the active ingredients and components that inhibiting cathepsin K activity in Erzhi Wan, a classic kidney-tonifying formula. Methods Then-butanol, dichloromethane, ethyl acetate and petroleum ether parts and 30 active components in Erzhi Wan were screened by established high throughput fluorescence methods of inhibit the binding activity of CTSK with Z-FR-MCA substrate, the formation of CTSK and chondroitin sulfate A (CSA) complex activity, and the activity of substrate type I collagen degradation by CTSK. Molecular docking and insoluble collagen substrate binding assays were applied to verify the potential CTSK inhibitors. Results The n-butanol and petroleum ether parts of Erzhi Wan inhibited the formation of CTSK and CSA^* complex by more than 90%, the petroleum ether part inhibited the binding of CTSK to substrate Z-FR-MCA by more than 90%, the collagen degradation inhibition rate of CTSK in n-butanol part was more than 95% and that in petroleum ether part was 58.6%. Among the 30 active components, 11 showed that the inhibition rate of CTSK and CSA^* complex formation was more than 50%, and 5 components with the inhibition rate of Z-FR-MCA binding activity more than 50%. Finally, there were four components including eclalbasaponin Ⅸ, (-)-epicatechin gallate, nuezhenoside and wedelolactone. The inhibition rate of collagen degradation was more than 50%. Eclipta saponin IX inhibited the binding rate between collagen fibers and CTSK, up to 60%, but all of them failed to dock with CTSK active site. Conclusion There are active components that inhibiting cathepsin K in Erzhi Wan, which mainly exists in the n-butanol ingredients, but the active components is not an active-site inhibitor. It might inhibit the binding of CTSK with oligosaccharides by binding to other sites of CTSK, and then reduce the collagen degradation activity of CTSK.

Objective: To analyze the association between body mass index (BMI) and coronary heart disease. Methods: The data for the present study were from the prospective cohort study of China Kadoorie Biobank (CKB) in Qingdao, a total of 33 355 participants aged 30-79 years were included in the study. Cox regression analyses were performed to evaluate the association between BMI and coronary heart disease. Results: During the follow-up for an average 9.2 years, a total of 2 712 cases of ischemic heart disease (IHD) and 420 cases of major coronary events (MCE) were found. Multivariate Cox regression analysis showed that, compared with participants with normal BMI, the participants who were overweight had a 41% and 87% higher risk of IHD and MCE, the adjusted HR were 1.41 (95%CI: 1.27-1.56) and 1.87 (95%CI: 1.43-2.44), respectively. The participants who were obesity had 91% and 143% higher risk of IHD and MCE, the adjusted HR were 1.91 (95%CI: 1.72-2.13) and 2.43 (95%CI: 1.82-3.24), respectively. Conclusion: Overweight and obesity might increase the risk for IHD and MCE.
Body Mass Index ; Coronary Disease/epidemiology* ; Humans ; Myocardial Ischemia/epidemiology* ; Obesity/epidemiology* ; Overweight/epidemiology* ; Prospective Studies

Objective:To summarize the experience on accurate prevention and control of children′s emergency department during the epidemic of novel coronavirus Omicron variant.Methods:We retrospectively analyzed the strategies and management experience of emergency prevention and control of novel coronavirus infection in emergency department at Children′s Hospital of Fudan University from March to May 2022.Results:As a designated hospital for treating pediatric patients who contracted novel coronavirus in Shanghai, the emergency department in our hospital was confronted with the dual pressure of critical patients treatment and pandemic prevention and control.We carefully studied a series of laws and regulations, as well as the newest edition of Chinese clinical guidance for novel coronavirus pneumonia diagnosis and treatment, and combined with the characteristics of novel coronavirus infection in children, then formulated the independent emergency department, fever clinics and novel coronavirus clinics; Updated the emergency department pre-examination triage process, the precautions pratice of clinical stuffs and disfection strategy, and established the second emergency department.From the beginning of March to the end of May 2022, a total of about 12 000 patients were admitted to the emergency department in our hospital, including 704 patients in the resuscitation room, 652 patients in the observation room, and 164 patients in the emergency ward.There were six patients with novel coronavirus infection in the emergency department.Neither nosocomial infection nor occupational exposure occurred.Conclusion:After 3 months of practice, the results showed that it can fully guarantee the timely treatment of critically ill children and achieved zero cross-infection in the hospital, which has important reference significance for the treatment of children, epidemic prevention, control during the novel coronavirus epidemic.