BACKGROUND: Chronic kidney disease (CKD)-associated anemia (CKD-anemia) is associated with poor survival, and hemoglobin targets are often not achieved with current therapies. Phase 3 trials have demonstrated the treatment efficacy of roxadustat for CKD-anemia. This phase 4 study aims to evaluate the long-term (52-week) safety and effectiveness of roxadustat in a broad real-world patient population with CKD-anemia with and without dialysis in China. METHODS: This Phase 4 multicenter, open-label, prospective study, conducted from 24 November 2020 to 11 November 2022, evaluated the long-term safety and effectiveness of roxadustat for CKD-anemia in China. Patients aged ≥18 years with CKD-anemia with or without dialysis were included. The initial oral dose was 70-120 mg (weight-based followed by dose adjustment) over 52 weeks. The primary endpoint was safety based on adverse events (AEs). The secondary endpoints were hemoglobin changes from baseline and the proportion of patients who achieved mean hemoglobin ≥100 g/L. Effectiveness evaluable populations 1 (EE1) and EE2 included roxadustat-naïve and previously roxadustat-treated patients, respectively. The safety analysis set (SAF) included all patients who received ≥1 occasion. RESULTS: The EE1, EE2, and SAF populations included 1804, 193, and 2021 patients, respectively. In the SAF, the mean age was 50 ± 14 years, and 1087 patients (53.8%) were male. Mean baseline hemoglobin was 96.9 ± 14.0 g/L in EE1 and 100.3 ± 12.9 g/L in EE2. In EE1, the mean (95% confidence interval) hemoglobin changes from baseline over weeks 24-36 and 36-52 were 14.2 (13.5-14.9) g/L and 14.3 (13.5-15.0) g/L, respectively. Over weeks 24-36 and 36-52, 83.3% and 86.1% of patients in EE1 and 82.7% and 84.7% in EE2 achieved mean hemoglobin ≥100 g/L, respectively. In the SAF, 1643 (81.3%) patients experienced treatment-emergent AEs (TEAEs). Overall, 219 (10.8%) patients experienced drug-related TEAEs. Thirty-eight (1.9%) patients died of TEAEs (unrelated to the study drug). Vascular access thrombosis was uncommon. CONCLUSIONS: Roxadustat (52 weeks) increased hemoglobin and maintained the treatment target in Chinese patients with CKD-anemia with acceptable safety, supporting its use in real-world settings. REGISTRATION Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100046322; CDE ( www.chinadrugtrials.org.cn ) CTR20201568.
Humans ; Male ; Female ; Anemia/etiology* ; Middle Aged ; Renal Insufficiency, Chronic/complications* ; Glycine/adverse effects* ; Isoquinolines/adverse effects* ; Aged ; Prospective Studies ; Adult ; Hemoglobins/metabolism* ; Treatment Outcome ; China ; Registries ; East Asian People

BACKGROUND:The biological behavior of mesenchymal stem cells is influenced by the survival microenvironment.Pre-treatment of the microenvironment is an important means of regulating the function of mesenchymal stem cells. OBJECTIVE:To compare the differences in paracrine function of umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells under oxidative stress and hypoxia,and to provide a theoretical basis for selecting appropriate pretreatment of mesenchymal stem cells to treat different diseases. METHODS:Umbilical cord mesenchymal stem cells and adipose mesenchymal stem cells were cultured by H2O2 or O2 oxygen,respectively,and cell morphology,proliferation,viability and paracrine factor expression were examined. RESULTS AND CONCLUSION:(1)The expression levels of brain-derived neurotrophic factor and transforming growth factor-β were higher in umbilical cord mesenchymal stem cells than in adipose mesenchymal stem cells under a normal culture environment,while the expressions of stromal cell-derived factor-1α and tumor necrosis factor stimulating factor-6 in the adipose mesenchymal stem cells were significantly higher than those in the umbilical cord mesenchymal stem cells.(2)There was no significant difference in the effect of low and moderate levels(≤100 μmol/L)of H2O2 on the viability of the two mesenchymal stem cells.However,increasing the H2O2 concentration from 50 μmol/L to 100 μmol/L resulted in a distinct increase in vascular endothelial growth factor expression in umbilical cord mesenchymal stem cells.The expression of basic fibroblast growth factor,vascular endothelial growth factor,stromal cell-derived factor-1α and interleukin-10 in adipose mesenchymal stem cells was greatly increased by increasing H2O2 concentration in this range.(3)1%O2 hypoxia promoted mesenchymal stem cell proliferation.After 24 hours of culture in 1%O2,gene expression levels were elevated in both mesenchymal stem cells,but the expression levels of vascular endothelial growth factor,interleukin-10 and tumor necrosis factor stimulating factor-6 were significantly higher in adipose mesenchymal stem cells than in umbilical cord mesenchymal stem cells.(4)It is concluded that hypoxia and oxidative stress preconditioning enhances the paracrine function of mesenchymal stem cells.However,mesenchymal stem cells respond differently to hypoxia and oxidative stress.Treating diseases can choose suitable mesenchymal stem cells for appropriate pretreatment to further enhance their therapeutic potential.

The acupoint sensitization theory,a breakthrough in acupuncture and moxibustion over the past two decades,has greatly enhanced the understanding of meridians and acupoints while increasing the effectiveness of clinical diagnosis and treatment in acupuncture and moxibustion practices.The number of studies on surface sensitization site detection for different diseases is increasing.However,systematic sorting and a summary of the detection mode of surface sensitization points are lacking.Therefore,this study categorizes the method of surface sensitization point detection into two modes:pan-scanning and focused scanning.The classification is based on the characteristics of the openness of the research purpose,the precision of the target range,and the degree of variation during detection.The two modes have considerable differences in the exploration efficiency and the presentation of result.The pan-scanning mode can be further subdivided into holistic and localized pan-scanning modes,whereas the focused-scanning mode can be subdivided into fixed-and variable-focused scanning modes.This study analyzes the application scenarios,characteristics,advantages,and limitations of each detection mode and presents opinions on mode selection,mode innovation,and future development directions.This study aims to provide valuable insights and guidance for the follow-up research on surface sensitization site detection of various diseases.

As China enters the aging era, the incidence rate and prevalence of inflammatory bowel disease(IBD)in the elderly have increased.The relationship between aging and inflammation appears to be more significant in elderly individuals with IBD.However, most current studies focus on describing the clinical characteristics of the disease, with limited research on its pathogenesis and treatment.In this review, we summarize the differences in clinical characteristics and treatment between elderly individuals with IBD and young individuals.We also discuss the impact of aging on elderly IBD and explore the possibility of stem cell transplantation therapy as a new approach for clinical management.Our aim is to provide fresh insights for the treatment of elderly IBD.

This article introduced the research design and main results of the article " Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults with Obesity: A 10-Year Follow-up of a Randomized Clinical Trial" recently published in JAMA Internal Medicine, and addressed the scientific significance of the study. The importance of obesity management has been well discussed recently. This study investigated obesity management strategies for obese individuals and their long-term metabolic benefits.

Objective:To explore the relationship between personality characteristics, social psychology and satisfactory rate in people undergoing facial cosmetic surgery.Methods:People undergoing facial cosmetic surgery who were admitted to the First Affiliated Hospital of Naval Medical University from February 2021 to February 2022 were seclected. They were asked to fill out the Big Five Inventory (abbreviated version), social psychological factors questionnaire before surgery, and the surgical satisfaction scale 2 weeks after surgery. According to the results of surgical satisfaction, they were divided into satisfied group and dissatisfied group. The distribution of personality characteristics and social psychological factors was analyzed, univariate analysis and logistic multiple regression were used to analyze the personality characteristics and social psychological factors affecting the satisfaction result.Results:There were 217 cases, including 9 males and 208 females, aged 18-45 years old with an average age of 26 years old. According to the operation satisfaction survey, 174 cases were satisfied and 43 cases were dissatisfied. Among the personality characteristics of 217 cases, low agreeableness, high responsibility, high extraversion, low openness, and high neuroticism accounted for the majority; there were statistically significant differences in agreeableness, extraversion, openness, and neuroticism between the satisfied group and the dissatisfied group( P<0.05); but in the comparison of responsibility, there was no statistically significant difference between the two groups ( P>0.05). Among the psychosocial factors of 217 cases, female, aged 18-28 years, with a bachelor’s degree or above, a vocational student or employee, urban registered residence, with a medium income, with a history of plastic surgery, following the doctor’s advice, moderate expectation, surgery suggestion with family members account for the majority; the results of univariate analysis show that the satisfied group and the dissatisfied group were compared in terms of age, education level, monthly income, surgical cost, previous plastic surgery history, and expected effect, the difference was statistically significant ( P<0.05); however, there was no statistically significant difference in gender, marital status, occupation, nature of household registration, choice of surgery, surgery recommended by family members, and consultation in multiple hospitals ( P>0.05). The results of logistic regression analysis showed that low agreeableness, low extraversion, high neuroticism, low age, high education level, and high expectation were independent risk factors affecting the surgical satisfaction( P<0.05). Conclusion:Personality characteristics (low agreeableness, low extraversion, high neuroticism) and social psychological factors (low age, high education level, high expectation) are independent risk factors of surgical satisfaction in people undergoing facial cosmetic surgery.

Objective:To explore the relationship between personality characteristics, social psychology and satisfactory rate in people undergoing facial cosmetic surgery.Methods:People undergoing facial cosmetic surgery who were admitted to the First Affiliated Hospital of Naval Medical University from February 2021 to February 2022 were seclected. They were asked to fill out the Big Five Inventory (abbreviated version), social psychological factors questionnaire before surgery, and the surgical satisfaction scale 2 weeks after surgery. According to the results of surgical satisfaction, they were divided into satisfied group and dissatisfied group. The distribution of personality characteristics and social psychological factors was analyzed, univariate analysis and logistic multiple regression were used to analyze the personality characteristics and social psychological factors affecting the satisfaction result.Results:There were 217 cases, including 9 males and 208 females, aged 18-45 years old with an average age of 26 years old. According to the operation satisfaction survey, 174 cases were satisfied and 43 cases were dissatisfied. Among the personality characteristics of 217 cases, low agreeableness, high responsibility, high extraversion, low openness, and high neuroticism accounted for the majority; there were statistically significant differences in agreeableness, extraversion, openness, and neuroticism between the satisfied group and the dissatisfied group( P<0.05); but in the comparison of responsibility, there was no statistically significant difference between the two groups ( P>0.05). Among the psychosocial factors of 217 cases, female, aged 18-28 years, with a bachelor’s degree or above, a vocational student or employee, urban registered residence, with a medium income, with a history of plastic surgery, following the doctor’s advice, moderate expectation, surgery suggestion with family members account for the majority; the results of univariate analysis show that the satisfied group and the dissatisfied group were compared in terms of age, education level, monthly income, surgical cost, previous plastic surgery history, and expected effect, the difference was statistically significant ( P<0.05); however, there was no statistically significant difference in gender, marital status, occupation, nature of household registration, choice of surgery, surgery recommended by family members, and consultation in multiple hospitals ( P>0.05). The results of logistic regression analysis showed that low agreeableness, low extraversion, high neuroticism, low age, high education level, and high expectation were independent risk factors affecting the surgical satisfaction( P<0.05). Conclusion:Personality characteristics (low agreeableness, low extraversion, high neuroticism) and social psychological factors (low age, high education level, high expectation) are independent risk factors of surgical satisfaction in people undergoing facial cosmetic surgery.

Objective:To analyze risk factors for diabetes mellitus in patients with vitiligo, and to construct and validate a prediction model.Methods:A total of 110 vitiligo patients with diabetes mellitus (comorbidity group) and 4 505 vitiligo patients without diabetes mellitus (control group) were collected from the medical record database in Xijing Hospital, the Fourth Military Medical University from January 2010 to October 2021, and matched for gender and age at a ratio of 1∶4 by using a propensity score method. After matching, the matched pairs were randomly divided into a training set and a test set at a ratio of 4∶1. Univariate and multivariate logistic regression analyses were used to assess demographic and clinical characteristics of patients in the training set, screen differential factors, and construct a prediction model. A five-fold cross-validation method was used for internal validation after construction of the prediction model. The discrimination (area under the curve [AUC]) , calibration (Hosmer-Lemeshow test) and accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) of the prediction model were evaluated in the test set.Results:A total of 107 cases in the comorbidity group and 428 cases in the control group were successfully matched. The training set included 430 cases, and the test set included 105 cases. Based on multivariate logistic regression results, a total of 6 factors were included in the prediction model, including course of vitiligo (odds ratio [ OR] = 1.04, 95% confidence interval [ CI]: 1.02 - 1.07, P<0.001) , high-sugar/high-fat/high-salt diet ( OR = 3.19, 95% CI: 1.38 - 7.38, P = 0.007) , family history of diabetes ( OR = 23.23, 95% CI: 9.72 - 55.50, P<0.001) , metabolic comorbidities ( OR = 12.53, 95% CI: 5.60 - 28.07, P<0.001) , autoimmune comorbidities ( OR = 5.89, 95% CI: 2.52 - 13.76, P<0.001) , and acral vitiligo ( OR = 3.84, 95% CI: 1.45 - 10.19, P = 0.007) . Five-fold cross-validation results showed a good predictive performance of the prediction model, with the AUC being 0.902 (95% CI: 0.864 - 0.940) in the training set and 0.895 (95% CI: 0.815 - 0.974) in the test set. The prediction model also showed favourable discrimination (AUC =0.814, 95% CI: 0.715 - 0.913) , calibration (Hosmer-Lemeshow test, P = 0.068) , and accuracy (sensitivity = 0.810, 95% CI: 0.574 - 0.937; specificity = 0.786, 95% CI: 0.680 - 0.865; positive predictive value = 0.486, 95% CI: 0.317 - 0.657; negative predictive value = 0.943, 95% CI: 0.853 - 0.982) in the test set. Conclusion:A risk prediction model was constructed for diabetes mellitus in patients with vitiligo based on 6 factors (course of vitiligo, high-sugar/high-fat/high-salt diet, family history of diabetes, metabolic comorbidities, autoimmune comorbidities, and acral vitiligo) , which showed favourable discrimination, calibration and accuracy, and might provide a reference for screening the high-risk diabetic population in vitiligo patients.

Objective:To evaluate the effect of anatomic resection (AR) and nonanatomic resection (NAR) on the prognosis of hepatocellular carcinoma (HCC) patients of China Liver Cancer Staging (CNLC) Ⅰa.Methods:PubMed, Embase and Cochrane Library databases were searched for articles on AR and NAR of CNLC Ⅰa stage HCC from January 2000 to March 2021. A meta-analysis was performed on patient characteristics, tumor characteristics, surgical procedures, postoperative pathological characteristics and long-term prognosis.Results:Of 9 case-control studies were included in this study, there were 2761 patients, with 1727 cases in the AR group and 1034 cases in the NAR group. When compared with the NAR group, the AR group had lower proportion of liver cirrhosis, lower ICG R15 value, higher proportion of Child-Pugh A grade, larger tumor diameter, higher proportion of microvascular invasion, longer operation time and higher intraoperative blood loss. The AR group had a better postoperative 5-year disease-free survival rate [ OR=1.54, 95% CI: 1.30-1.82, P<0.001] and a higher postoperative 5-year overall survival rate [ OR=1.27, 95% CI: 1.04-1.55, P=0.018]. Conclusion:AR is significantly better than NAR for preventing long-term recurrence and improving long-term survival in patients with CNLC Ⅰa stage HCC.

Objective: To investigate the ameliorative effects of Mushroom on adipose tissue inflammation and glucolipid metabolism in mice fed a high-fat diet, and to provide a theoretical basis for the mechanisms of Mushroom regulating glucolipid metabolism and inflammatory responses. Methods: C57 BL/6 J mice were fed with normal diet(LF) group, high-fat diet(HF)group and high-fat diet + Mushroom(HF+Mushroom) group for 15 weeks.Then, body weight subcutaneous and epididymal white adipose tissue weight were measured. The morphological changes of adipose tissues were compared by HE staining, and the expression of genes related to inflamation, glycolysis and fatty acid oxidation pathways were detected by RT-PCR and Western blot. Results: Compared with the LF group, the HF group had increased body weight, increased subcutaneous and epididymal white fat weight and adipocyte size, and upregulated expression of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), monocyte chemoattractant protein-1(MCP-1), CD68, inducible nitric oxide synthase(iNOS), pyruvate kinase(PK), phosphofructokinase(PFK), hypoxia inducible factor-1α(HIF-1α) and peroxisome proliferator activated receptor alpha(PPARα) in adipose tissues, while the expression of carnitine palmitoyl transferase-1 A(CPT-1 A), cytochrome P450 4 a10(CYP4 a10) and medium-chain acyl-coenzyme a dehydrogenase(MCAD) were downregulated(P<0.05). Compared with the HF group, Mushroom supplementation reduced body weight, adipose tissue weight and adipocyte size, and downregulated the expression of pro-inflammatory factors and glycolytic pathway-related factors in adipose tissues, while the expression of fatty acid oxidation pathway-related factors were upregulated(P<0.05). Conclusion Mushroom can ameliorate inflammation and disorders of glycolipid metabolism in adipose tissues of obese mice.