腰痹通胶囊与布洛芬缓释胶囊联合用药治疗慢性腰痛疗效的随机对照研究

摘要 目的：观察腰痹通胶囊与布洛芬缓释胶囊联合用药治疗慢性腰痛的临床疗效。方法：将168例在我院门诊接受治疗的慢性腰痛患者随机分为A组、B组与C组（各56例）,A组给予口服腰痹通胶囊 (3粒/次),3次/d,饭后服药;B组给予布洛芬缓释胶囊治疗 (300 mg/次),2次/d,饭后口服;C组同时口服腰痹通胶囊和布洛芬缓释胶囊（用法同前）,3组均治疗1个疗程。观察治疗前后3组患者的临床疗效、视觉模拟评分（VAS）、Oswestry功能障碍指数（ODI）评分、日本骨科协会腰椎治疗评价量表（JOA）评分、血清炎性因子和药物副作用等各项指标,并进行对比分析。结果：所有患者均完成了研究,没有退出或脱落病例。A组的总有效率为76.79%,B组的总有效率为82.14%,C组的总有效率为96.43%,经统计学分析,AB两组之间没有显著的统计学差异（P>0.05）,而C组与A组或B组之间均有显著性差异（P<0.05）。3组的VAS、ODI、JOA评分在治疗前后具有显著的统计学差异（P<0.05）,其中C组治疗后的相关评分优于其他两组（P<0.05）。C组患者治疗后的炎性因子包括C反应蛋白(CRP)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平均低于A组、B组(P<0.05)。A组的药物副作用最少,B组的药物副作用最多,A组和C组的不良反应发生率低于B组（P<0.05）。结论：腰痹通胶囊联合布洛芬缓释胶囊口服治疗慢性腰痛的疗效明显优于这两种药物单独使用,可缓解患者腰部疼痛,改善腰椎功能,降低血清炎性因子水平。     

心脏彩超检查联合血清BNP、ALB、CysC在慢性心力衰竭患者预后评估中的临床价值分析

摘要 目的：分析心脏彩超检查联合血清B型钠尿肽（BNP）、白蛋白（ALB）、胱抑素C（CysC）在慢性心力衰竭（CHF）患者预后评估中的临床价值。方法：选取2017年6月-2018年5月我院收治的123例CHF患者,心脏彩超检查左心室射血分数（LVEF）、左心房内径（LAD）和左心室内径（LVD）,实验室检测血清BNP、ALB、CysC水平。按照3年随访后患者是否死亡分为死亡组35例和存活组88例,收集临床资料,采用多因素Logistic回归分析CHF患者预后的影响因素。采用受试者工作特征（ROC）曲线分析心脏彩超检查联合血清BNP、ALB、CysC对CHF患者预后的评估价值。结果：死亡组患者的LAD、LVD及血清BNP、CysC水平高于存活组患者,而LVEF及血清ALB水平低于存活组患者（P＜0.05）。心脏彩超指标LVEF、LAD、LVD及血清BNP、ALB、CysC是CHF患者预后的影响因素（P＜0.05）。心脏彩超指标LVEF、LAD、LVD联合血清BNP、ALB、CysC检测对CHF患者预后评估的ROC曲线下面积（AUC）（0.95CI）为0.857（0.771～0.938）,灵敏度及特异度分别为0.914（32/35）、0.795（70/88）,均明显高于上述各指标单独检测。结论：心脏彩超指标LVEF、LAD、LVD和血清BNP、ALB、CysC均为CHF患者预后的影响因素,且联合检测对患者预后的评估价值较高,具有一定的临床应用价值。     

Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation

Chronic cystitis is characterized by the hyperplasia and fibrosis of the bladder wall as well as attenuated compliance of the bladder. To further unravel its underlying molecular mechanism, the role of NFκB-JMJD3 signaling pathway in cystitis induced bladder fibrosis was investigated. Jmjd3 and Col1/3 expression was detected in a cystitis mouse model that was developed by intraperitoneal injection of cyclophosphamide (CYP). Human bladder smooth muscle cells (hBSMCs) were stimulated in vitro with lipopolysaccharide (LPS), and the cell proliferation and collagen accumulation were detected using EdU, CCK8, flow cytometry, qPCR, western blotting and immunofluorescence assays. Furthermore, the effects of NFκB and JMJD3 on cell proliferation and collagen accumulation were investigated using its selective antagonists, JSH23 and GSK-J4, respectively. CYP induced cystitis significantly increased Jmjd3, Col1 and Col3 expression in the bladder muscle cells. Furthermore, LPS stimulation markedly activated NFκB signaling and elevated JMJD3 expression in hBSMCs, and the activation of NFκB-JMJD3 signaling significantly promoted cell proliferation and collagen accumulation by upregulating CCND1 and COL1/3 expression, respectively. Our study reveals the critical role of NFκB-JMJD3 signaling in cystitis induced bladder reconstruction by regulating hBSMC proliferation and extracellular matrix (ECM) deposition, and these findings provide an avenue for effective treatment of patients with cystitis.     

Atypical activation of signaling downstream of inactivated Bcr-Abl mediates chemoresistance in chronic myeloid leukemia

Chronic myeloid leukemia (CML) epitomises successful targeted therapy, where inhibition of tyrosine kinase activity of oncoprotein Bcr-Abl1 by imatinib, induces remission in 86% patients in initial chronic phase (CP). However, in acute phase of blast crisis, 80% patients show resistance, 40% among them despite inhibition of Bcr-Abl1 activity. This implies activation of either Bcr-Abl1- independent signalling pathways or restoration of signalling downstream of inactive Bcr-Abl1. In the present study, mass spectrometry and subsequent in silico pathway analysis of differentiators in resistant CML-CP cells identified key differentiators, 14–3-3ε and p38 MAPK, which belong to Bcr-Abl1 pathway. Their levels and activity respectively, indicated active Bcr-Abl1 pathway in CML-BC resistant cells, though Bcr-Abl1 is inhibited by imatinib. Further, contribution of these components to resistance was demonstrated by inhibition of Bcr-Abl1 down-stream signalling by knocking-out of 14–3-3ε and inhibition of p38 MAPK activity. The observations merit clinical validation to explore their translational potential.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12079-021-00647-x.     

基于微生态探讨肠源性尿毒症毒素与慢性肾脏病的关系

近年来得益于宏基因组学和代谢组学研究技术的进步,人类健康或疾病状态下,肠道菌群与宿主相关性研究剧增,但其潜在机制研究仍然处于初级阶段。以慢性肾脏病(chronic kidney disease, CKD)为研究背景,大量证据表明患者宿主和肠道菌群之间存在双向关联。一方面,CKD的病理状态下存在特殊的肠道菌群代谢模式;另一方面,肠道菌群紊乱及分解代谢后产生的肠源性尿毒症毒素(gut-derived uremic toxins, GDUT)也加速CKD进展。因此,本文着重探讨硫酸吲哚酚、硫酸对甲酚和氧化三甲胺等关键GDUT对CKD患者结肠转运时间、肾转运体和自清除作用的潜在作用机制。进而从微生态角度出发,提出优化膳食摄入、调节肠道菌群等肾保护性措施,为延缓CKD的进展提供新的治疗思路。     

Nephrotoxicity after radionuclide therapies

Radioligand therapies have opened new treatment avenues for cancer patients. They offer precise tumor targeting with a favorable efficacy-to-toxicity profile. Specifically, the kidneys, once regarded as the critical organ for radiation toxicity, also show excellent tolerance to radiation doses as high as 50–60 Gy in selected cases. However, the number of nephrons that form the structural and functional units of the kidney is determined before birth and is fixed. Thus, loss of nephrons secondary to any injury may lead to an irreversible decline in renal function over time. Our primary understanding of radiation-induced nephropathy is derived from the effects of external beam radiation on the renal tissue. With the growing adoption of radionuclide therapies, considerable evidence has been gained with regard to the occurrence of renal toxicity and its associated risk factors. In this review, we discuss the radionuclide therapies associated with the risk of nephrotoxicity, the present understanding of the factors and mechanisms that contribute to renal injury, and the current and potential methods for preventing, identifying, and managing nephrotoxicity, specifically acute onset nephropathies.     

Hepatitis E Virus: An emerging enigmatic and underestimated pathogen

Hepatitis E virus (HEV) is an RNA virus causing hepatitis E disease. The virus is of one serotype but has diverse genotypes infecting both humans and animals. Based on evidence from seroprevalence studies, about 2 billion people are estimated to have been infected with HEV globally. HEV, therefore, poses a significant public health and economic challenge worldwide. HEV was discovered in the 1980s and was traced back to the 1955 – 1956 outbreak of hepatitis that occurred in India. Subsequently, several HEV epidemics involving thousands of individuals have occurred nearly annually in different countries in Asia and Africa. Initially, the virus was thought to be only enterically transmitted, and endemic in developing countries. Due to the environmental hygiene and sanitation challenges in those parts of the world. However, recent studies have suggested otherwise with the report of autochthonous cases in industrialised countries with no history of travel to the so-called endemic countries. Thus, suggesting that HEV has a global distribution with endemicity in both developing and industrialised nations. Studies have also revealed that HEV has multiple risk factors, and modes of transmission as well as zoonotic potentials. Additionally, recent findings have shown that HEV leads to severe disease, particularly among pregnant women. In contrast to the previous narration of a strictly mild and self-limiting infection. Studies have likewise demonstrated chronic HEV infection among immunocompromised persons. Consequent to these recent discoveries, this pathogen is considered a re – emerging virus, particularly in the developed nations. However, despite the growing public health challenges of this pathogen, the burden is still underestimated. The underestimation is often attributed to poor awareness among clinicians and a lack of routine checks for the disease in the hospitals. Thus, leading to misdiagnosis and underdiagnosis. Hence, this review provides a concise overview of epidemiology, diagnosis, and prevention of hepatitis E.     

Comparison of pulmonary vascular response to endogenous nitric oxide inhibition in sheep and pigs living at 2,300 m

To compare the role of nitric oxide in an adaptive process to chronic hypoxia, we examined the effects of endogenous nitric oxide synthase inhibition on pulmonary vascular tone in conscious sheep and pigs living at high altitude. Unanesthetized male sheep (n=6) and pigs (n=5), born and residing in the highlands of Qinghai Province, China (2,300–3,000 m a.s.l.) were studied at that altitude. Pulmonary artery pressure (P_pa), pulmonary artery wedge pressure (P_cwp), and cardiac output (CO) were measured. Pulmonary vascular resistance (PVR) was calculated as (P_pa—P_cwp)/CO. Using a climatic chamber, hemodynamic measurements during exposures to atmospheric pressures corresponding to altitudes of 0, 2,300, and 4,500 m a.s.l. were performed with and without NO inhibition, using N^w-nitro-l-argine (NLA; 20 mg kg^–1), a potent stereospecific competitive inhibitor of nitric oxide synthase. P_pa and PVR at baseline (2,300 m) and during hypoxic exposure (4,500 m) were significantly higher in pigs than in sheep. After NLA administration, P_pa increased and CO decreased in both animals, resulting in significantly increased PVR at baseline and during hypoxic exposure. However, there were no significant differences in the percent increase in basal or hypoxic PVR after NLA administration between sheep and pigs. We conclude that augmented endogenous NO production could contribute to the regulation of pulmonary vascular tone at high altitude in sheep and pigs. However, it is unlikely that NO is responsible for the different pulmonary vascular tones between sheep and pigs at basal condition at moderately high altitude.Communicated by G. Heldmaier