Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-beta and iguratimod or SRC inhibitors in vitro, suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage-myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.

Clinical diagnostic reasoning is one of the contents of clinical thinking methods, and it is used throughout the clinical work. Clinical diagnosis reasoning is an important part of clinical professional curriculum teaching for educators and plays an important role in clinical education. Clinical education focuses on how to effectively cultivate clinical diagnostic reasoning ability in the teaching of clinical professional courses. Based on previous research, clinical diagnostic reasoning instruction can be divided into three categories: the importance of clinical diagnostic reasoning instruction, teaching content, teaching methods, and evaluation methods. It is hoped that by combining clinical professional courses, medical students will be trained in their clinical thinking mode at the undergraduate and graduate levels, as well as their clinical diagnostic reasoning ability, allowing them to have a more profound study and application of clinical course contents, and lay a solid foundation for later clinical practice.

Introduction: Idiopathic systemic capillary leak syndrome (SCLS) is a rare disorder characterized by hemoconcentration, hypoproteinemia and edema. Chronic SCLS (cSCLS) presents as intractable edema, distinguishing it from the classic acute form, and only about 10 cases were reported worldwide. Nevertheless, the underlying pathogenesis of both types is obscure.Case presentation: We report a case of a 58-year-old man with chronic edema persisting for 8 years, complicated by unique chylous polyserous effusions and hypotrichosis, which was successfully relieved by treatment with dexamethasone, intravenous immunoglobulin, and thalidomide. Furthermore, a variant c.5594A>G (p.K1865R) in the MYOF gene was identified as a potentially pathogenic mutation through whole-exome genetic sequencing. The proposed mechanism involves its impact on VEGF signaling, leading to increased capillary permeability.Conclusion: Our case illustrates possible lymphatic capillaries involvement in SCLS, which may plays a potential role in immune disorder, and revealed a possible causative genetic mutation of SCLS.

The molecular mechanisms underlying lupus nephritis (LN) pathogenesis are not fully understood. Hydrogen sulfide (H2S) is involved in many pathological and physiological processes. We sought to investigate the roles of H2S in LN pathogenesis. H2S synthase cystathionine-lyase (CSE) and cystathionine-synthetase (CBS) expression was downregulated in renal tissues of patients with LN and their levels were associated with LN's prognosis using the Nephroseq database. Reduced CSE and CBS protein expression in kidney tissues of LN patients and MRL/lpr mice were confirmed by immunohistochemistry. CSE and CBS mRNA levels were reduced in MRL/lpr and pristine- and R848-induced lupus mice. Given that H2S exerts an anti-inflammatory role partly via regulating inflammatory transcription factors (TFs), we analyzed hub TFs by using a bioinformatics approach. It showed that STAT1, RELA, and T-cell-related signaling pathways were enriched in LN. Increased STAT1 and RELA expression were confirmed in renal tissues of LN patients. Treatment of MRL/lpr and pristine mice with H2S donors alleviated systemic lupus erythematosus (SLE) phenotypes and renal injury. H2S donors inhibited RELA level and T-cell infiltration in the kidneys of MRL/lpr and pristine mice. Our data indicated that CSE/CBS/H2S contributes to LN pathogenesis. Supplementation of H2S would be a potential therapeutic strategy for LN.

总结1例获得性易栓症合并全身多发皮损患者的症状管理体会.针对患者反复血栓形成和多处皮损迁延不愈且不断进展的问题,采取评估—解释—管理—监测—关注细节模式进行症状管理.评估引起反复血栓与皮损的多重病因,包括原发疾病、抗凝不足、深静脉血栓并发症等.根据评估结果进行病因治疗,调整抗凝药物并监测抗凝效果及不良反应,预警肺栓塞的发生,伤口中心会诊处理复杂皮损问题.鼓励患者及家属参与医疗护理决策,提高对治疗护理的依从性.经过23 d的精心治疗与护理,患者血红蛋白、D-二聚体等各项指标趋于正常,血栓未继续进展,全身皮损有效控制后顺利出院.

背景与目的:假性Kaposi肉瘤,又称肢端血管性皮炎,是一种罕见的血管外科疾病.本文通过报告1例静脉瓣功能障碍致假性Kaposi肉瘤病例,结合文献回顾探讨其临床病理特征及诊治.方法:回顾性分析1例假性Kaposi肉瘤患者的临床病例资料,结合国内外文献总结假性Kaposi肉瘤的病因、分型、临床表现、病理、诊断及治疗.结果:患者男性,37岁.长期从事站立性体力劳动,两踝关节内侧下方数个暗紫红色瘀斑,近1个月久站后皮损处疼痛.结合病史、病理切片及辅助检查,诊断为"假性Kaposi肉瘤".经穿弹力袜、促进静脉回流、抗凝、改善循环后,双下肢皮损处无明显疼痛,皮损较前无明显扩大或增多.结论:静脉瓣功能障碍与假性Kaposi肉瘤发生发展相关,较为罕见且鉴别诊断存在一定困难,需结合皮损特点、病理及血管影像特点综合考虑,目前无特异性治疗.

Introduction Metabolic risks including high body mass index, high fasting plasma glucose, high low-density lipoprotein cholesterol, high systolic blood pressure, kidney dysfunction and low bone mineral density, contribute heavy burden to the US health systems. We aimed to investigate the burden attributable to metabolic risks in the US from 1990 to 2019. Methods Using methodology of Global Burden of Disease Study, the deaths and DALYs attributable to metabolic risks were analyzed by age, gender, states, Socio-demographic Index (SDI) and diseases from 1990 to 2019 in the US. Results In 2019, the age-standardized death and DALY rates attributable to metabolic risks were 174.9 and 4738.7 per 100,000 people, accounting for 33.1% and 18.2% of death and DALY rates from all causes in the US, and there was a decrease by −32.5% and −21.2% in age-standardized death and DALY rates since 1990. The burden attributable to metabolic risks increased with age, and was higher in males than females. In addition, the burden varied widely across the states, generally in inverse proportion to the SDI levels, and the heaviest burden was observed in East and West South-Central of the US. Cardiovascular diseases carried heavy burden attributable to metabolic risks. Conclusion The burden attributable to metabolic risks remained major public health concerns in the US. Prevention of metabolic risks should be a high priority in the US.

Diagnostics is one of the most important bridge courses for medical students from basic to clinical. Doctor-patient communication runs through the whole process of patient diagnosis and treatment. How to improve medical students' ability of doctor-patient communication? Our teaching team has carried out continuous reform and explored the scientific effective teaching mode. Recently, through the construction of "doctor-patient communication skills" quality online course, efforts have made to build an online and offline blended learning mode, which has gradually realize the integration with diagnostics teaching, and has achieved remarkable results. It also provides a scientific practical basis for the integration of doctor-patient communication and other clinical courses, which is worthy of promotion.

Intracerebral hemorrhage (ICH) is a disease with a significantly high rate of morbidity, mortality and disability. Inhibition of inflammation is considered a potential strategy for improving the clinical symptoms induced by ICH. The hallmark of neuroinflammation is microglial activation. Microglia can polarize into either the classically activated M1 (proinflammatory) phenotype, exacerbating neuronal damage, or the alternatively activated M2 (antiinflammatory) phenotype, exerting neuroprotection and promoting neuronal recovery. Promoting microglial polarization to the M2 phenotype may be a viable strategy for treating neuroinflammation. Several studies have indicated that promoting blood circulation and removing blood stasis exhibits therapeutic effects on intracerebral hemorrhage. Dahuang Zhechong Pill (DHZCP), a classical recipe that promotes blood circulation and removes blood stasis, has been reported to improve the clinical outcome of ICH. DHZCP has been shown to exert antiinflammatory effects. However, the detailed antiinflammatory mechanism of DHZCP in ICH has rarely been investigated. In this study, DHZCP inhibited lipopolysaccharide (LPS)-induced M1 microglial activation. DHZCP exerted antiinflammatory effects, by inhibiting LPS-induced M1 proinflammatory cytokine (TNF-α and IL-6), and iNOS production and increasing M2 antiinflammatory cytokine (IL-10) production. DHZCP also switched microglial polarization from M1 to M2, as indicated by significantly increased expression of M2 polarization markers (CD209, and CD206) and markedly decreased expression of an M1 polarization marker (CD54). In addition, DHZCP inhibited p38 and TLR4/NF-κB signaling activation, as demonstrated by inhibition of LPS-induced increases in p-p38, TLR4 and nuclear factor kappa B p-65 (NF-κB p-65) protein expression. Taken together, DHZCP modulates microglial M1/M2 polarization via the p38 and TLR4/NF-κB signaling pathways to confer antiinflammatory effects.

OBJECTIVE To observe the effect of enalapril on the apoptosis of renal tubular epithelial cells in renal interstitial fibrosis rats and to explore the mechanism of enalapril on renal interstitial fibrosis.
 Methods: Twenty-four SD male rats were randomly divided into a sham operation group, a model group and an enalapril group (n=8 in each group). The rats in the model group and the enalapril group underwent the operation of left urethral obstruction to establish the animal model of unilateral urethral obstruction (UUO). Fourteen days later after the operation, all rats were sacrificed and their obstructed kidneys were collected for HE and Masson staining to observe the pathological change of renal tissues. Terminal deoxynucleotidyl transferase-mediated (dUTP) nick end-labeling (TUNEL) staining was used to detect the apoptosis of renal tubular epithelial cells. Immunohistochemistry and Western blotting were used to detect the protein expression of Fas-associated death domain (FADD), apoptotic protease activating factor-1 (APAF-1) and C/EBP homologous protein (CHOP).
 Results: Compared with the sham operation group, the renal interstitial injury index and renal interstitial fibrosis index were significantly increased in the model group (P<0.05). Compared with the model group, the renal interstitial injury index and renal interstitial fibrosis index were both significantly decreased in the enalapril group (P<0.05). Compared with the sham group, the apoptosis rate of renal tubular epithelial cells was increased in the model group (P<0.05); compared with the model group, the apoptosis rate of renal tubular epithelial cells was significantly reduced in the enalapril group (P<0.05). The protein levels of FADD, APAF-1 and CHOP in the model group were significantly elevated than those in the sham group (all P<0.05), which were reversed in presence of enalapril (all P<0.05). 
 Conclusion: Enalapril can alleviate renal interstitial fibrosis through inhibiting apoptosis of renal tubular epithelial cells in UUO rats.

This study aimed to investigate the mechanism of fluorofenidone (AKF-PD) in treating renal interstitial fibrosis in rats with unilateral urinary obstruction (UUO). Thirty-two male Sprague-Dawley rats were randomly divided into sham, UUO, UUO + enalapril, and UUO + AKF-PD groups. All rats, except sham, underwent left urethral obstruction surgery to establish the animal model. Rats were sacrificed 14 days after surgery, and serum was collected for renal function examination. Kidneys were collected to observe pathological changes. Immunohistochemistry was performed to assess collagen I (Col I) protein expression, and terminal deoxynucleotidyl transferase-mediated nick end-labeling staining to observe the apoptosis of renal tubular epithelial cells. The expression of Fas-associated death domain (FADD), apoptotic protease activating factor-1 (Apaf-1), and C/EBP homologous protein (CHOP) proteins was evaluated by immunohistochemistry and western blot analysis. AKF-PD showed no significant effect on renal function in UUO rats. The pathological changes were alleviated significantly after enalapril or AKF-PD treatment, but with no significant differences between the two groups. Col I protein was overexpressed in the UUO group, which was inhibited by both enalapril and AKF-PD. The number of apoptotic renal tubular epithelial cells was much higher in the UUO group, and AKF-PD significantly inhibited epithelial cells apoptosis. The expression of FADD, Apaf-1, and CHOP proteins was significantly upregulated in the UUO group and downregulated by enalapril and AKF-PD. In conclusion, AKF-PD improved renal interstitial fibrosis by inhibiting apoptosis of renal tubular epithelial cells in rats with UUO.

Fibrosis is a common pathology in renal disease. Hypertensive nephropathy (HN) is one of the most common secondary nephropathies that often progresses to severe renal fibrosis with limited treatment options beyond hypertension control. Bromodomain-containing protein 4 (Brd4) was recently recognized as a target in signaling pathways that underlie the pathologies of inflammatory diseases and tumors. A recently developed inhibitor of Brd4, JQ1, has been shown to exert antifibrotic effects and is being clinically explored as an anti-inflammatory and antitumor drug. Here, using human kidney biopsies and Angiotensin II-induced mouse fibrotic kidney samples, we show that Brd4 was upregulated in renal tissue from HN patients and hypertensive mouse models. In mice, JQ1 alleviated Angiotensin II-induced kidney fibrosis and blocked epithelial-mesenchymal transition (EMT) by altering the expression of EMT-related proteins. Using an in vitro model of HK2 cells exposed to Angiotensin II, we also demonstrated that JQ1 suppressed the protein expression of fibrotic genes in these cells. These results further implicate Brd4 in the fibrotic response in HN and reveal that Brd4 is a potential antifibrotic target. BET inhibitors are currently being investigated in clinical trials as antitumor agents and show potent pharmacological effects. Our findings suggest that BET inhibitors may also be potential translational therapies for HN.

Renal fibrosis is a key pathological feature in chronic kidney diseases (CKDs). Dysregulation of hydrogen sulfide (H2S) homeostasis is implicated in the pathogenesis of CKDs. Here, C57/BL6 mice were allocated to Sham and unilateral ureteral obstruction (UUO) groups, which were treated with NaHS or NLRP3 inflammasome inhibitor 16673-34-0 for 3–14 days. UUO mice displayed downregulation of H2S production and increased macrophage infiltration in obstructed kidneys. H2S donor NaHS treatment attenuated renal damage and fibrosis and inhibited M1 and M2 macrophage infiltration. NLPR3 inflammasome was activated and levels of phosphorylated nuclear factor κB (NF-κB) p65 subunit, phosphorylated signal transducer and activator of transcription 6 (STAT6) and interleukin (IL)-4 protein were increased in the kidneys after UUO. NLRP3 inhibitor inactivated NF-κB and IL-4/STAT6 signaling, suppressed M1 and M2 macrophage infiltration and attenuated renal damage and fibrosis in UUO mice. NaHS treatment also suppressed NLRP3, NF-κB and IL-4/STAT6 activation in the obstructed kidneys. In conclusion, the therapeutic effects of H2S on UUO-induced renal injury and fibrosis are at least in part by inhibition of M1 and M2 macrophage infiltration. H2S suppresses NLRP3 activation and subsequently inactivates NF-κB and IL-4/STAT6 signaling, which may contribute to the anti-inflammatory and anti-fibrotic effects of H2S.

Objective To investigate the correlation between neutrophil-lymphocyte ratio (NLR) and disease activity of systemic lupus erythematosus (SLE),and the changes of NLR in different organ involvement of SLE patients.Methods A total of 155 SLE patients and 135 healthy controls from the Rheumatology Department of Xiangya Hospital were enrolled in this study from 2010 to 2018.Patients with SLE were divided into lupus nephritis group (LN group) and non-lupus nephritis group (non-LN group),serositis group and non-serositis group,according to whether they had kidney involvement or serositis.According to the SLE disease activity index 2000(SLEDAI-2000),the patients were divided into mild to moderate disease activity group (SLEDAI score ＜ 15) and severe disease activity group (SLEDAI score≥ 15).The NLR values of the above groups were compared.Spearman's correlation analysis was used to analyze the correlation between NLR and SLE patients' laboratory indexes.Multiple linear regression model was used to analyze the relationship between NLR and SLE disease activity.Receiver operating characteristic curve (ROC) was used to evaluate the value of NLR in SLE diagnosis and activity assessment.Results (1)The NLR value of SLE patients was significantly higher than that of healthy control group,and the difference was statistically significant (P ＜ 0.01).(2)The NLR value of SLE patients in the LN group was higher than that in the non-LN group,and the NLR value of SLE patients with serositis was higher than that in the group without serositis,with statistically significant differences (both P ＜ 0.05).(3)The NLR value of SLE patients in the severe disease activity group was higher than that in the mild and moderate disease activity group,and the difference was statistically significant (P ＜ 0.01).(4)NLR of SLE patients was positively correlated with CRP (rs=0.188,P=0.019),SLEDAI score (rs=0.264,P=0.001),and negatively correlated with total serum protein (rs=-0.250,P=0.002) and serum albumin (rs=-0.329,P ＜ 0.001),respectively.(5) Multiple linear regression showed that NLR was independently associated with SLE disease activity (B=0.351,95％CI 0.012-0.690,t=2.047,P=0.042).(6) According to ROC curve,the optimal cut-off value of NLR for SLE diagnosis was 2.17 (sensitivity 60.0％,specificity 83.1％,AUC=0.744),and the best cut-off value for predicting the activity of severe disease activity in SLE patients was 3.28 (sensitivity 58.5％,specificity 78.1％,AUC=0.700).Conclusion NLR is closely related to renal involvement,serositis and disease activity in SLE patients,which indicates that NLR,as a new inflammatory indicator,is of great significance for the assessment of SLE disease activity and organ involvement.

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种好发于育龄期女性的慢性自身免疫性疾病,狼疮危象是指急性的危及生命的重症SLE.妊娠可使SLE患者病情加重,甚至诱发狼疮危象.早期识别和规范化治疗妊娠期狼疮危象,是抢救患者生命的关键.

OBJECTIVE:To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).
 Methods: All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.
 Results: In the 10-year time period, the overall hospital mortality was 15.68‰. The disease itself accounted for 44.71% of the total causes of death, infection accounted for 42.94%, and comorbidities accounted for 12.35%. The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year, and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05). In 2013-2014, infection was the leading cause of death, which accounted for 51.06%. The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD, and even the risk of death was 1.722 times of the latter. The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus, that by infection was the highest in idiopathic inflammatory myopathy (IIM), and that by comorbidities was the highest in rheumatoid arthritis.
 Conclusion: The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend, while the proportion of deaths caused by infection and comorbidities increase. CTDs patients with ILD have shorter survival time and an increase in risk of death.

Objective To investigate the clinical characteristics of systemic lupus erythematosus (SLE) with normal serum IgG levels. Methods A retrospective study of 259 newly diagnosed SLE patients was conducted to compare extrarenal clinical manifestations, renal manifestations, erythrocyte sedimentation rate (ESR), high sensitivity C-reactive protein (hs-CRP), immunological indexs and SLEDAI scores between normal serum IgG levels group and increased serum IgG levels group. The correlation of serum IgG levels to serum C3, serum C4 and SLEDAI scores was analyzed. The correlation of serum IgG levels to urinary protein and urinary IgG levels was analyzed too. Results Normal serum IgG levels group had lower incidences of non-infectious fever, alopecia, arthritis and anemia ( <0.05) while higher incidences of thrombocytopenia ( <0.05). Incidences of lupus nephritis were similar between the two groups. However, normal serum IgG levels group had higher levels of urinary protein and urinary IgG ( <0.05), except higher incidences of nephrotic proteinuria and hematuria ( <0.05). The levels of urinary protein and urinary IgG were negative correlated with serum IgG levels ( <0.05). The levels of ESR and hs-CRP in Normal serum IgG levels group were lower than those in increased serum IgG levels group ( <0.01). Normal serum IgG levels group had lower levels of serum IgG, IgA and IgM ( <0.01), except lower positive rate of ANA, dsDNA, Sm and AnuA ( <0.05). There was no significant difference in the serum C3 levels, the incidences of decreased serum C3 level and the SLEDAI scores between the two groups ( <0.05). Serum IgG levels was not correlated with serum C3, serum C4 and SLEDAI scores ( <0.05). Conclusions The active SLE patients with normal serum IgG levels is not rare. In these patients, the renal damage is more obvious relatively and the positive rate of the SLE-related autoantibody is lower than the SLE patients who have high serum IgG levels. The serum IgG levels is not correlated with the lupus disease activity.

Introduction: Insufficient tissue oxygen (O2) availability (hypoxia) is commonly seen in patients with cardiovascular diseases (CVD) ,chronic kidney diseases (CKD), respiratory diseases and certain cancers. Although erythrocyte is the only cell type responsible for delivering and sensoring O2, its function in pathological tissue hypoxia remains largely unknown. Hypothesis: Erythrocyte A2B adenosine receptor (ADORA2B) plays a key protective role in Ang II-induced tissue damage by increasing 2,3-biphosphoglycerate(2, 3-BPG) and oxygen release to counteract tissue hypoxia. Methods: We infused angiotensin II (Ang II, 140ng/kg/min) to mice with specific deletion of ADORA2B in erythrocytes (ADORA2B f/f /EpoR-Cre + ) for 14 days and measured the levels of 2,3-BPG,P50,p-AMPK in erythrocytes of mild and severe CKD patients. Results: We found that 2,3-BPG, an erythrocyte-specific metabolite enhancing O2 delivery, was significantly induced in the erythrocytes of mice infused with Ang II. Mouse genetic studies demonstrated that Ang II induced local tissue accumulation of adenosine and that elevated adenosine-mediated erythrocyte ADORA2B activation was beneficial by inducing 2,3-BPG production, triggering O2 release to counteract tissue hypoxia, heart and kidney damage including proteinuria along with the mRNA levels of collagen I, fibronectin, prepro-ET-1 and endothelin receptor type A, which are known tissue damage associated genes. Mechanistically, we revealed that AMPK is an intracellular signaling molecular functioning downstream of ADORA2B underlying elevated 2,3-BPG production by inducing BPG mutase activity and protects tissue hypoxia, kidney dysfunction and renal fibrosis. Finally, we translated our mouse study to human and confirmed that the levels of 2,3-BPG, P50 and p-AMPK were elevated in erythrocytes of hypertensive CKD patients compared to healthy individuals and correlated to disease severity. Conclusions: We demonstrate that erythrocyte ADORA2B-mediated AMPK activation plays a key protective role in Ang II-induced tissue damage by increasing 2, 3-BPG and oxygen release to counteract tissue hypoxia and immediately suggest novel therapies for hypertension and CKD.

Introduction: It is widely accepted that macrophage recruitment and polarization play a prominent role in the development of renal fibrosis. Our previous studies have demonstrated that persistently...

留学生高等医学教育已成为衡量高等医学院校教育水平的重要标志之一.诊断学作为临床桥梁课程,对于临床医生培养有着举足轻重的作用.我院内科学、诊断学教研室从课前准备、利用多媒体授课、PBL+ TBL+ LBL教学方法及"小讲课"、"小老师"授课比赛等一系列教学手段等方面进行探讨,为提高留学生诊断学教学质量提供可借鉴的思路.