IntroductionCardiovascular disease represents the leading cause of mortality among patients with chronic kidney disease (CKD). CKD-associated cardiomyopathy is characterized by pathological left ventricular hypertrophy and myocardial fibrosis. Pegmolesatide, a novel pegylated continuous erythropoietin receptor activator, has demonstrated efficacy in treating renal anemia. However, the biological effects of Pegmolesatide beyond erythropoiesis remain poorly characterized.MethodsThis study established a 5/6 nephrectomy rat model of CKD. The animals were randomized into four groups: sham-operated (Sham), sham-operated plus Pegmolesatide (Sham + Pegmolesatide), CKD model (CKD), and CKD model plus Pegmolesatide (CKD + Pegmolesatide). Cardiac function was assessed by echocardiography, while histopathological examination evaluated cardiac and renal structural changes. Serum renal function parameters were measured using biochemical assays. Myocardial expression of proteins and mRNAs related to fibrosis, hypertrophy, and associated signaling pathways was analyzed by Western blot and quantitative PCR. Furthermore, transcriptomic sequencing of myocardial tissue was performed, and in vitro experiments were conducted using AC16 human cardiomyocytes stimulated with serum from stage 5 CKD patients.ResultsTranscriptomic sequencing suggested that the cardioprotective effects of Pegmolesatide might be associated with improved mitochondrial function and modulation of the STAT3 signaling pathway. Results demonstrated that Pegmolesatide significantly improved cardiac functional parameters and attenuated both myocardial fibrosis and cardiomyocyte hypertrophy. Mechanistic investigations revealed that these cardioprotective effects were mediated through inhibition of JAK2/STAT3 signaling pathway activation and concomitant improvement of mitochondrial function.DiscussionThese findings demonstrate that pegmolesatide exerts anti-anemic effect-independent cardioprotection, offering novel insights into treating CKD-associated cardiomyopathy.

INTRODUCTION:Renal anemia is one of the most common complications in dialysis patients. The shortened red blood cell (RBC) lifespan is an important mechanism of renal anemia. This study aims to investigate the RBC lifespan and its influencing factors in anemic dialysis patients. METHOD:Prevalent patients on maintenance hemodialysis or peritoneal dialysis, treated with anti-anemia therapy including recombinant human erythropoietin (rHuEPO) or roxadustat for more than 4 months were enrolled. RBC lifespan was measured by the RBC lifespan analyzer RBCS-01A depended on Levitt's carbon monoxide (CO) breath test. Participants were primarily divided into low and high RBC lifespan groups by the average value. RESULT:A total of 187 patients were included in this study. The average RBC lifespan was 65.2 ± 28.55 days. The logistic regression analysis indicated treating with roxadustat rather than rHuEPO [OR 2.94, 95% CI (1.46, 5.95), p < 0.01], male [OR 2.15, 95% CI (1.08, 4.29), p = 0.03], higher body mass index (BMI) [OR 1.17, 95% CI (1.07, 1.27), p < 0.01], and higher total iron-binding capacity (TIBC) [OR 1.04, 95% CI (1.01, 1.06), p = 0.01] were independent risk factors for the shorten of RBC lifespan. While higher adjusted calcium [OR 0.14, 95% CI (0.03, 0.70), p = 0.02] and older age [OR 0.96, 95% CI (0.94, 0.99), p = 0.01] were independent protective factors. CONCLUSION:This study demonstrated that independent risk factors contributing to this reduction in RBC lifespan include male, elevated BMI, increased TIBC, and decreased adjusted calcium levels. Additionally, the type of anti-anemia therapy administered appears to have an impact on RBC lifespan.

Emerging biologics that selectively target key cytokines present a promising therapeutic alternative for patients suffering from severe, uncontrollable chronic rhinosinusitis with nasal polyps (CRSwNP). Despite the limited availability of registered biologics for CRSwNP treatment in China, the country is experiencing rapid development in this field. It is imperative to standardize the application of biologic agents in CRSwNP management in preparation for their future integration into the CRSwNP care pathway. The Rhinology Group, Chinese Society of Otorhinolaryngology-Head and Neck Surgery; the Rhinology Group, Chinese Medical Doctor Association of Otorhinolaryngology-Head and Neck Surgery; and the Nasal and Ocular Allergy Group, Chinese Society of Allergy have convened an expert panel consisting of principal investigators experienced in clinical trials of biologic treatment for CRSwNP. This expert panel was assembled to discuss the application of biologic agents in patients with CRSwNP in China. Additionally, the latest findings on the pathogenesis of CRSwNP, mechanisms of biologic agents, and efficacy and safety of biologic treatment in patients with CRSwNP were reviewed, with a special emphasis on research evidence from China. The expert panel reached a consensus on several critical issues, including criteria for the prescription, treatment course, and efficacy evaluation from a Chinese perspective. This position paper aims to guide Chinese physicians in the use of biologic agents for patients with CRSwNP. As our experience with biologic treatment continues to grow, this position paper will be further updated.

BACKGROUND:Cardiovascular events remain the leading cause of mortality in chronic kidney disease (CKD). Pegmolesatide(P), a novel long-acting EPO receptor modulator, shows cardiovascular benefits in clinical studies. This study aims to demonstrate Pegmolesatide suppressed the formation of EPOR-CD131 heterodimer and to explore its cardioprotective mechanisms against indoxyl sulfate (IS)-induced cardiomyocyte hypertrophy. METHODS:H9c2 cardiomyocytes were assigned to different treatment groups (vehicle, IS, IS+P, P) and RNA sequencing was performed to identify dysregulated signaling pathways. Mechanistic exploration groups supplemented with CD131 agonist ARA290, STAT3 activator Colivelin, or STAT3 inhibitor Stattic for rescue experiments. Analyses included real-time qPCR/Western blot for cardiac hypertrophy markers and EPOR-CD131/JAK2/STAT3 axis components, phalloidin staining for cell size and co-immunoprecipitation (Co-IP) for EPOR-CD131 heterodimerization. RESULTS:Pegmolesatide significantly attenuated IS-induced cardiomyocyte hypertrophy, as evidenced by suppressed expression of cardiac hypertrophy markers (ANP, BNP, and β-MHC), reduced cell surface area, and improved cytoskeletal organization(P < 0.05). Mechanistically, Pegmolesatide upregulated EPOR expression while suppressing CD131 expression and activation of the JAK2/STAT3 signaling. Co-IP analysis demonstrated that Pegmolesatide suppressed the formation of EPOR-CD131 heterodimer. Functional rescue experiments showed that the cardioprotective effects of Pegmolesatide were reversed by CD131 agonist ARA290 or STAT3 activator Colivelin. Notably, combined treatment with ARA290 and STAT3 inhibitor Stattic partially restored its anti-hypertrophic activity. CONCLUSION:Pegmolesatide exerts protective effects against IS-induced cardiomyocyte hypertrophy by inhibiting the EPOR-CD131/JAK2/STAT3 signaling axis. It may be a promising strategy for CKD-related cardiovascular complications.

Introduction: This study aimed to evaluate the predictive value of the low-frequency/high-frequency (LF/HF) ratio in all causes of death and hospitalizations in maintenance hemodialysis (MHD) patients. Methods: This is a single-center prospective study with a 48-h electrocardiograph (ECG) recording. A total of 110 patients were enrolled in the study from October 1, 2021, to September 30, 2022. ECG recordings started before initiation of the hemodialysis (HD) session and lasted for 48 h, covering the intra- as well as inter-HD period. We divided our participants into two groups based on the median value of LF/HF, one of the frequency domain parameters of heart rate variability (HRV). Patients with LF/HF <1.33 were categorized as group A and those with LF/HF >= 1.33 were group B. The endpoint of the study was a composite event of death or hospitalization. We followed all patients until the composite endpoint or the end of the study on February 28, 2023. Multivariate Cox regression was used to assess the adjusted effect of LF/HF on the composite endpoint. Results: Patients in group A were older and the number of patients with diabetes was more than that of group B. With regards to the laboratory data, group A had lower serum creatinine and uric acid and higher ferritin and NT-ProBNP. In the index HD session, systolic blood pressure was higher but diastolic blood pressure was significantly lower in group A. During the median follow-up period of 8.8 (7.6-9.8) months, 27 hospitalizations and 10 deaths were documented. Increased LF/HF ratio was an independent protective factor of composite endpoint events (HR = 0.357, 95% CI: 0.162-0.790, p = 0.011). Conclusion: Risks of mortality and hospitalizations are higher among HD patients having decreased LF/HF ratios. LF/HF in the 48-h recording can be considered as a prognostic factor for risk stratification in HD patients.

Introduction: Disordered iron balance and abnormal parathyroid hormone (PTH) concentrations, both prevalent in hemodialysis patients, are risk factors of erythropoietin (EPO) resistance. Few studies have evaluated the correlation between iron indices and PTH and the potential role of iron markers on the association of PTH with EPO resistance in hemodialysis population. Methods: In this cross-sectional study of 71 maintenance hemodialysis patients, iron indices including hepcidin, ferritin, reticulocyte hemoglobin content (CHr), and transferrin saturation (TSAT) were examined. EPO responsiveness was measured as EPO resistance index (ERI). Lowess regression curves were performed to explore the correlations of iron indices, PTH, and ERI. The association between PTH and ERI was modeled using linear regressions. Potential role of iron indices on this association was examined using stratified analyses and mediation analyses. Results: The average ERI value was 10.3 ± 5.3 IU w−1 kg−1 (g/dL) −1. ERI was correlated to PTH, hepcidin, CHr, and TSAT (all p < 0.05). Hepcidin and PTH were closely correlated with each other (r = 0.28, p = 0.020). Analysis by PTH categories yielded a total association effect of 2.53 (95% CI: 0.27–4.85, p = 0.027) for high PTH subgroup versus the reference low subgroup. No clinically significant interaction between iron indexes and PTH was identified. Hepcidin appeared to mediate about one-third of the total association between PTH and ERI in hemodialysis population (33.6%, p = 0.025). Conclusion: Iron indices and PTH levels were related to ERI values. Hepcidin appeared to be closely correlated to PTH and partly mediate the association between PTH and ERI in hemodialysis population.

目的 探讨腹膜透析(peritoneal dialysis,PD)患者胸腹瘘的临床特征及诊治.方法 入选北京大学人民医院肾内科PD中心2006年1月1日～2021年9月30日确诊胸腹瘘的患者,收集一般资料、PD方案、胸腹瘘症状、体征、实验室检查、确诊方法、治疗及转归进行分析.结果 ①共纳入胸腹瘘患者5例,发生率0.96％.②5例胸腹瘘均在透析3～13周增加单次存腹剂量过程中发生,均为右侧,80％为女性,女性、老年高龄、低体表面积可能为危险因素.临床多表现为胸闷、呼吸困难、超滤减少等.③诊断方法:胸片提示右侧中到大量胸腔积液.可通过胸水葡萄糖高于血糖、亚甲蓝注入试验或CT腹腔造影确诊.④治疗方式:确诊后立即暂停PD转为血液透析(hemodialysis,HD),部分患者永久转至HD,或通过低剂量递增性PD逐渐恢复并长期PD治疗.结论 胸腹瘘为PD少见并发症,常在开始透析后增加单次存腹剂量的过程中发生,CT腹腔造影己成为最简便有效的确诊方式,治疗上需暂停PD,转为HD,或通过低剂量递增性恢复PD.如条件许可,手术治疗是解决胸腹瘘的有效措施.在透析液增量过程中应密切监测高危患者胸腹瘘相关症状体征、腹腔内压力变化,并减少目标存腹剂量,以预防胸腹瘘的发生.

Abstract Background Osteoporosis is a very common skeletal disorder that increases the risk of fractures. However, the treatment of osteoporosis is challenging. Hypoxia-inducible factor-1α (HIF-1α) plays an important role in bone metabolism. Roxadustat is a novel HIF stabilizer, and its effects on bone metabolism remain unknown. This study aimed to investigate the effects of roxadustat on osteoblast differentiation and bone remodeling in an ovariectomized (OVX) rat model. Methods In vitro, primary mouse calvarial osteoblasts were treated with roxadustat. Alkaline phosphatase (ALP) activity and extracellular matrix mineralization were assessed. The mRNA and protein expression levels of osteogenic markers were detected. The effects of roxadustat on the HIF-1α and Wnt/β-catenin pathways were evaluated. Furthermore, osteoblast differentiation was assessed again after HIF-1α expression knockdown or inhibition of the Wnt/β-catenin pathway. In vivo, roxadustat was administered orally to OVX rats for 12 weeks. Then, bone histomorphometric analysis was performed. The protein expression levels of the osteogenic markers HIF-1α and β-catenin in bone tissue were detected. Results In vitro, roxadustat significantly increased ALP staining intensity, enhanced matrix mineralization and upregulated the expression of osteogenic markers at the mRNA and protein levels in osteoblasts compared with the control group. Roxadustat activated the HIF-1α and Wnt/β-catenin pathways. HIF-1α knockdown or Wnt/β-catenin pathway inhibition significantly attenuated roxadustat-promoted osteoblast differentiation. In vivo, roxadustat administration improved bone microarchitecture deterioration and alleviated bone loss in OVX rats by promoting bone formation and inhibiting bone resorption. Roxadustat upregulated the protein expression levels of the osteogenic markers, HIF-1α and β-catenin in the bone tissue of OVX rats. Conclusion Roxadustat promoted osteoblast differentiation and prevented bone loss in OVX rats. The use of roxadustat may be a new promising strategy to treat osteoporosis.

数字时代管理实践中的无限链接、动态协同、范围经济、不确定性等特征向现有管理理论提出了巨大挑战,实践界需要新的"范式革命"来帮助组织有效地应对数字化.为了解读数字时代组织面临的新困惑,帮助企业应对数字时代的新挑战,本文提出了协同共生论.协同共生是指组织共生单元通过主动寻求协同增效,实现边界内组织成长、跨边界组织成长和系统自进化,进而达到整体价值最优的动态过程.协同共生的本质是从无序到有序,协同共生论就是用于引导共生单元实现整体价值最优的理论和方法体系,即通过协同共生效应、架构、管理模型及价值重构关键要素的管理理论和方法,帮助企业实现边界内组织成长、跨边界组织成长、系统自进化,进而达到整体价值最优.本文提出组织内共生、组织外共生及组织内外共生等三种共生态结构,并探讨了实现三种结构的机理、要素、模型与情境条件."协同共生论"作为协同逻辑、共生状态的有机融合,为探索数字时代的组织和管理理论提供了新的可能.

BACKGROUND:Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown. OBJECTIVES:To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 μg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14-17 y compared with offspring with no supplementation. METHODS:Two geographic sites in China from the 1993-1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35-54 y) and 15 y among adolescents (range: 14-17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva. RESULTS:In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values < 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values < 0.05). CONCLUSIONS:Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

Objective:To evaluate the application of virtual reality technology in the teaching of otolaryngology anatomy for eight-year program medical students.Methods:The subjects were 33 senior medical students enrolled in 2017 in Peking University. 16 students in the control group were trained with traditional teaching methods while 17 students in the experimental group were supplemented with virtual reality technology combined with traditional teaching. The teaching effect of two groups was evaluated by questionnaire survey, theoretical examination and skill test of otolaryngology. T test and chi-square test were used to compare the difference between two groups.Results:12 students from experimental group and 4 students from the control group are very interested in learning otolaryngology anatomy ( P=0.032). Theoretical examination scores of experimental group(52.0±6.3) and control group(56.4±4.2) was statistically significant difference ( P=0.027). There is no statistical difference in skill test scores between two groups[(28.0±1.1) vs.(28.4±0.6), P=0.213]. Total scores of experimental group(80.1±6.4) and control group (84.8±4.5) was statistically significant difference ( P=0.019). Conclusions:The application of virtual reality technology in the anatomy teaching of Otorhinolaryngology training for eight-year program medical students may stimulate their learning interest and improve teaching effect.

脊索瘤是罕见的骨恶性肿瘤,起源于胚胎残留的脊索组织,过去认为脊索瘤相对于颅底更多见于骶骨,然而,现有证据表明,其在颅底( 32％)、脊柱(32.8％)和骶骨(29.2％)的分布几乎是均等的[1].虽然脊索瘤为低度恶性肿瘤,但易局部侵犯且预后不良.对于发生于斜坡的脊索瘤,目前公认的治疗原则是最大限度地安全地切除肿瘤,术中强调对神经及血管的保护,术后辅助放疗[2].本文报道1例侵犯海绵窦包绕颈内动脉的斜坡脊索瘤综合治疗结果.

Background To investigate the prevalence of left ventricular hypertrophy (LVH) and explore left ventricular geometry in maintenance hemodialysis (MHD) patients, and to explore the risk factors of LVH which is an important predictor of cardiovascular events. Methods The subjects were patients who are on MHD for more than 3 months in Peking University People's Hospital from March 2015 to February 2017. Demographic and clinical data were retrospectively collected. Left ventricular mass was measured by echocardiography. LVH is defined by Left ventricular mass index (LVMI) > 115 g/m(2) for men and > 95 g/m(2) in women. LVMI and relative wall thickness were used to determine left ventricular geometry. Logistic regression was used to analyze the risk factors of LVH. Results Altogether, 131 patients including 77 males were enrolled. The median age was 60 (47, 69) years, with a median dialysis vintage of 48 (18, 104) months. There were 80 patients with LVH, the prevalence rate was 61.1%, and 66.3% of them were moderate to severe LVH. We found that (1) most of the patients were concentric hypertrophy; (2) one-third of the patients were concentric remodeling; (3) only 4 cases with normal geometry. The pre-dialysis serum sodium level and time average pre-dialysis systolic blood pressure (SBP) were independent risk factors of LVH. Conclusion LVH is prevalent in MHD patients. Concentric hypertrophy and concentric remodeling are the most common geometric patterns. Attention should be paid to long-term pre-dialysis SBP management and pre-dialysis sodium control as they might be potentially modifiable risk factors for LVH.

目的 探讨罗沙司他对于维持性腹膜透析患者血压的影响.方法 采用回顾性自身对照研究,纳入2019年1月～2020年8月在北京大学人民医院肾内科规律随访、应用罗沙司他至少4个月且在应用罗沙司他前应用重组人红细胞生成素(recombinant human erythropoietin,rHuEPO)至少1年的维持性腹膜透析(peritoneal dialysis,PD)患者.将rHuEPO转换为罗沙司他的时间定义为基线时间,收集患者基线资料、应用罗沙司他后每个月的临床资料,共收集4个月,同时收集1年前同期患者应用rHuEPO期间的临床资料.比较应用罗沙司他后与基线时以及罗沙司他期间与1年前相同月份应用rHuE-PO期间患者的血压、血红蛋白(Hb)、降压药物剂量等的变化.结果 共38例PD患者纳入研究,基线收缩压(systolic blood pressure,SBP)为(144.6±18.5)mmHg,应用罗沙司他 1 月、2 月、3 月、4 月后,SBP分别为(139.2±17.5)mmHg、(134.3±15.9)mmHg、(137.4±16.9)mmHg和(137.2±14.5)mmHg,均较基线SBP 下降(1 月:t=2.285,P=0.028;2 月:t=3.408,P=0.002;3 月:t=2.223,P=0.032;4 月:t=2.521,P=0.030),降压药物的限定日剂量较基线无统计学差异.结论 排除了季节、容量、降压药物剂量等可能影响血压的因素后,PD患者将rHuEPO转换为罗沙司他,可有效避免rHuEPO相关血压升高.

为厘清创新网络联盟的内部机制,围绕国际创新网络联盟研究主题,运用CiteSpace V文献计量软件,采用科学计量学知识图谱研究方法,通过对Web of Science数据库中1 109篇文献进行统计分析,绘制创新网络联盟研究的知识图谱,进行发文时间、来源国家、研究机构、期刊共被引、高被引等分析,梳理国际创新网络联盟研究的前沿及演进.研究发现:国际创新网络联盟研究是较新的前沿研究,发文量呈逐年上升趋势,以欧美国家为主,美国的影响力最大;主要研究机构是大学,其中荷兰的大学占据重要地位;经管类国际顶级期刊如Research Policy等是领域内核心发文期刊;研究前沿热点为创新绩效、网络联盟、联盟组合、创新网络、知识创造、协同创新、开放式创新、突破式创新等.最后,提出未来研究可以从联盟组合的价值创造和价值分配机制与企业绩效的关系、联盟组合对创新联盟绩效的异质性,以及考虑伙伴相对议价能力、多边竞争水平、合作伙伴网络资源和谈判地位差异等方面进行.

高钾血症是血液透析(hemodialysis,HD)患者的常见并发症.患者的血钾可通过HD清除而快速下降,并于透析间期逐渐升高,直至下次HD,呈周期性变化.临床上我们常规监测HD结束即刻血钾,作为透析后血钾,用以评估透析充分性,对透析后数小时血钾研究较少.本文报道1例HD患者,因自体动静脉内瘘血栓形成更换血管通路为股静脉临时导管,后饮食未加控制,反复出现透析间期顽固性高钾血症,早期单用聚苯乙烯磺酸钙效果不佳,经加用环硅酸锆钠紧急降钾治疗联合HD成功诊治,为HD患者血钾长期管理提供理论依据.

目的:探讨内镜影像系统联合CBL教学法在耳鼻咽喉科学见习带教中的应用及效果.方法:将学生随机分为实验组(内镜影像系统联合CBL教学法)和对照组(传统教学法),通过理论考试及满意度调查进行教学效果评价.结果:实验组在理论总成绩及记忆、理解、应用三种题型的得分及教学满意度均高于对照组,差异具有统计学意义.结论:内镜影像系统联合CBL教学法有助于学生基础理论的理解和掌握,可提高耳鼻咽喉科见习教学效果.