Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis,synovial cell proliferation,neo-vascularization,and bone and cartilage destruction.Its pathogenesis is complex and has not yet been fully elucidated.A variety of cells,cytokines and signaling pathways are involved in the pathogenesis of RA.Hypoxia-inducing factor(HIF)and oxygen-sensing signaling pathway(PHD-HIF-VHL)are closely related to the occurrence and development of RA,and play an important role in syno-vial cell proliferation,inflammatory response and cartilage destruction.In this study,the research progress of oxygen sensing signaling pathway in RA was described from the aspects of the mechanism of oxygen sensing signaling pathway and its involvement in the patho-genesis of RA,in order to provide ideas and theoretical basis for the research of anti-RA drugs by targeting important molecules of oxy-gen sensing signaling pathway.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis,synovial cell proliferation,neo-vascularization,and bone and cartilage destruction.Its pathogenesis is complex and has not yet been fully elucidated.A variety of cells,cytokines and signaling pathways are involved in the pathogenesis of RA.Hypoxia-inducing factor(HIF)and oxygen-sensing signaling pathway(PHD-HIF-VHL)are closely related to the occurrence and development of RA,and play an important role in syno-vial cell proliferation,inflammatory response and cartilage destruction.In this study,the research progress of oxygen sensing signaling pathway in RA was described from the aspects of the mechanism of oxygen sensing signaling pathway and its involvement in the patho-genesis of RA,in order to provide ideas and theoretical basis for the research of anti-RA drugs by targeting important molecules of oxy-gen sensing signaling pathway.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To analyze the levels of antibody to measles virus in cord blood of newborns in Ankang city, and provide reference for the development of measles prevention and control measures and strategies.Methods:From January to December, 2023, 1 058 pregnant women from 10 county-level general hospitals in Ankang city were recruited in this study. Neonatal umbilical cord blood samples were collected for detecting IgG antibody against measles with ELISA. SPSS 21.0 software was used to analyze the positive rate of antibody to measles virus and the influencing factors.Results:The overall positive rate of IgG antibody to measles virus was 89.22% (944/1 058), and the geometric mean concentration (GMC) was 570.26 mlU/ml. The positive rates of IgG antibody against measles virus in umbilical cord blood of neonates born to women aged ≤20, 21-25, 26-30, 31-35, and ≥36 years old were 91.07% (51/56), 90.27% (232/257), 89.54% (351/392), 88.12% (230/261), and 86.96% (80/92), respectively (χ 2=1.355, P=0.852). Multivariate logistic regression analysis showed that the positive rate of IgG antibody against measles virus in umbilical cord blood samples was higher in neonates with gestational age ≥37 weeks than in those with gestational age <37 weeks [OR (95%CI): 0.403 (0.262-0.622)]. Besides, the positive rate was also higher in newborns with a birth weight of 3.0-3.5 kg than in those with birth weight <3 kg or ≥3.5 kg [OR (95%CI): 0.868 (0.462-1.629), 1.765(1.087-2.865)]. Conclusions:The positive rate and the GMC of IgG antibody to measles virus in neonatal umbilical cord blood decrease with maternal age. It is recommended that women of childbearing age should receive supplementary immunization with measles-containing vaccine before pregnancy.

Objective:To evaluate the mid-term results of fenestrated/branched endovascular aortic repair (f/b EVAR) for the treatment of thoracoabdominal aortic aneurysms. M ethods The clinical data of 105 thoracoabdominal aortic aneurysm patients treated with f/b EVAR at the Department of Vascular Surgery of Nanjing Drum Tower Hospital from 2018 to 2019 were retrospectively analyzed. Results:There were 43 cases of thoracoabdominal aortic aneurysm and 62 cases of thoracoabdominal aortic aissection.A total of 336 branch arteries were reconstructed,and technical success rate was 94.3%. 100 cases (95.2%) were followed-up, 6 cases (5.7%) received reoperation interventions, and 11 cases (10.5%) died. During the follow-up period, 69 cases had complete imaging data. Based on the recent CT date of the thoracoabdominal aorta, 58 patients hael positive aortic remodeling and 11 patients hael negative and indeterminate remodeling; there were 31 cases (29.5%) of endoleaks, including 7 cases (6.7%) of type Ⅰb endoleaks, 8 cases (7.6%) of type Ⅱ, 1 case (0.95%) of type Ⅲa, 13 cases (12.4%) of type Ⅲc endoleaks and 2 cases (1.9%) of type Ⅳ. Conclusions:The mid-term follow-up results were satisfactory for TAAA treated with f/b EVAR. Internal leakage remains key point for f/b EVAR.

Polymorphism refers to the simultaneous and frequent existence of two or more discontinuous variants or genotypes or alleles in a biological population, also known as genetic polymorphisms or genes Polymorphism. This gene polymorphism may have a certain degree of influence on the pharmacokinetics and pharmacodynamics of the drug. The study of genomics plays an important role in realizing personalized, patient-oriented precision medicine treatment. Population model analysis is to use a modeling method to quantitatively describe the correlation and variability between pharmacokinetic and pharmacodynamic parameters and individual characteristics and to quantify the impact of covariates. At present, this method has been widely used. This paper systematically introduces the application examples of using the population model approach to assess the effects of genetic polymorphisms on the drug PK/PD.

Objective:To evaluate the influence of cytomegalovirus (CMV) infection on T cell senescence and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients.Methods:It was a single center cross sectional study. Patients aged over 18 years old and received hemodialysis for at least 6 months at the Blood Purification Centre of the Department of Nephrology of Zhongshan Hospital Affiliated to Fudan University from January 2021 to April 2021 were enrolled. Demographic, hematological, nutritional and inflammatory markers were obtained. Anti-CMV-IgM and IgG antibodies were detected using the Roche Elecsys assay. CD28 - T cell was evaluated by flow cytometry. Mann-Whitney U test or Kruskal-Wallis H test was used for anti-CMV-IgG comparison among groups. Spearman correlation and linear regression were used to assess the relationship between anti-CMV-IgG and CD28 - T cell compartment. Logistic regression was used to assess the relationship between anti-CMV-IgG and CVD. Results:A total of 438 MHD patients (270 men and 168 women) were enrolled in the study. The median age was 62 (51, 70) years. The median time on hemodialysis was 57 (21, 100) months. The primary diseases included chronic glomerulonephritis [213 cases (48.6%)], diabetic nephropathy [82 cases (18.7%)], polycystic kidney disease [34 cases (7.8%)], hypertensive renal disease [34 cases (7.8%)], etc. Of these patients, 430 (98.2%) were seropositive for anti-CMV-IgG, 206 (47.0%) had anti-CMV-IgG titers exceeding the upper limit of 500 U/ml. Patients aged over 70 years old were 100% seropositive for anti-CMV-IgG. Patients on HD for more than 5 years had a higher seropositive rate of 99.1% than those with shorter HD duration, although these results were not statistically significant. Spearman correlation analysis showed that the anti-CMV-IgG titers in MHD patients were positively correlated with the proportion of CD4 + CD28 - T cells and CD8 + CD28 - T cells ( r=0.316, P<0.001; r=0.272, P<0.001). Multiple linear regression analysis showed that after adjusting for age and gender, lg[CD4 + CD28 - T cells(%)] and lg[CD8 + CD28 - T cells(%)] were positively correlated with lg[anti-CMV-IgG titers (U/ml)], respectively ( β=0.455, t=8.315, P<0.001; β=0.412, t=7.282, P<0.001). In analyzing the relationship between anti-CMV-IgG titers and CVD, patients were divided into six groups according to age and anti-CMV-IgG level. Group 1 included young patients with a lower anti-CMV-IgG titers (age ≤55 years old, anti-CMV-IgG <400 U/ml); Group 2 included young patients with a higher anti-CMV-IgG titers (age≤55 years old, anti-CMV-IgG ≥400 U/ml); Group 3 included middle-aged patients with a lower anti-CMV-IgG titers (5565 years old, anti-CMV-IgG<400 U/ml); Group 6 included old aged patients with a higher anti-CMV-IgG titers (age>65 years old, anti-CMV-IgG≥400 U/ml). The incidence of CVD was significantly different among the six groups ( χ2=18.780, P=0.002) and patients aged over 55 years old with higher anti-CMV-IgG level had a higher CVD incidence compared with group 1 ( P<0.05). Multivariate logistic regression analysis showed that increased age ( OR=1.020, 95% CI 1.002-1.038, P=0.033), male ( OR=1.855, 95% CI 1.161-2.965, P=0.010), history of diabetes ( OR=1.867, 95% CI 1.145-3.046, P=0.012), increased lg[NT-proBNP(μg/L)] ( OR=2.848, 95% CI 1.816-4.467, P<0.001) and lg[anti-CMV-IgG (U/ml)] ( OR=3.183, 95% CI 1.582- 6.405, P=0.001) were independent factors associated with CVD in MHD patients. Conclusions:CMV infection is extremely common in MHD patients. Increased anti-CMV-IgG is related to T cell senescence and CVD complications in MHD patients.

Drug safety is always the primary concern in both the stage of new drug development and the post-marketing clinical application stage, and it is also the main reason for drug development failure and even post-marketing drug withdrawal. The physiologically-based pharmacokinetic (PBPK) model can not only routinely predict the human plasma pharmacokinetics, but also predict the concentration distribution of drugs in different tissues, which has become an important tool for predicting the adverse reactions of new drugs and has gradually attracted the attention of drug regulatory authorities. In this article, the latest progress and application of the PBPK model for predicting drug-induced nephrotoxicity, cardiotoxicity, and neurotoxicity are briefly reviewed to provide references for early prediction of adverse drug reactions in new drug development and rational clinical use of drugs.

Drug safety is always the primary concern in both the stage of new drug development and the post-marketing clinical application stage, and it is also the main reason for drug development failure and even post-marketing drug withdrawal. The physiologically-based pharmacokinetic (PBPK) model can not only routinely predict the human plasma pharmacokinetics, but also predict the concentration distribution of drugs in different tissues, which has become an important tool for predicting the adverse reactions of new drugs and has gradually attracted the attention of drug regulatory authorities. In this article, the latest progress and application of the PBPK model for predicting drug-induced nephrotoxicity, cardiotoxicity, and neurotoxicity are briefly reviewed to provide references for early prediction of adverse drug reactions in new drug development and rational clinical use of drugs.