Organic anion transporter 1 (OAT1), primarily found in the renal proximal tubule, is essential for the excretion of various uremic toxins that contribute to the onset and progression of chronic kidney disease (CKD). OAT1 also plays a vital role in the remote sensing and signaling network, facilitating the removal of metabolites through the kidneys. The function of OAT1 is impaired under conditions such as renal ischemia/reperfusion injury, oxidative stress, and fibrosis. Several transcription factors, post-translational modifications, and endocrine hormones control the activity and expression of OAT1. This review explores the unique contribution of OAT1 to the excretion of CKD-related UTs and the mechanisms involved.

目的 比较HBeAg阳性慢性乙型病毒性肝炎(CHB)、乙型肝炎肝硬化、慢加急性肝衰竭患者牙周状况,探讨肝病的严重程度与牙周炎的相关性方法 收集2019年1月至2021年12月未经治疗且ALT≥2×ULN的HBeAg阳性CHB、乙型肝炎肝硬化失代偿期及HBsAg阳性基础上的慢加急性肝衰竭患者各60例,采用菌斑指数(PLI)、简化口腔卫生指数(OHI-S)、牙周炎分级等指标对各组患者进行牙周状况评估.结果 HBeAg阳性三组患者牙周炎分级比较差异有统计学意义(P＜0.05);乙型肝炎肝硬化组与慢加急性肝衰竭组患者牙周状况差异无统计学意义(P＞0.05).结论 乙型肝炎肝硬化患者牙周炎重于HBeAg阳性CHB患者,与慢加急性肝衰竭患者相当.

肝衰竭就是短时间内肝功能的迅速减退,快速进展的黄疸和凝血功能异常是其突出表现,所以中医学上多以急黄或瘟黄称之,如隋代大医家巢元方《诸病源候论·黄疸诸侯·急黄候》中就曾记载"脾胃有热,谷气郁蒸,因为热毒所加,故卒然发黄,心满气喘,命在顷刻,故云急黄也";急黄在发病过程中还可出现"血""鼓胀"及"肝厥"等变证.

慢性肝衰竭是指在肝硬化的基础上出现的肝功能进行性减退和失代偿,是我国肝病临床常见危重症,具有死亡率高和发病机制复杂的特点.临床研究表明,中西医结合治疗在改善慢性肝衰竭患者预后、降低死亡率方面具有优势.近年临床上基于"肾生髓,髓生肝"指导治疗慢性肝衰竭取得了显著效果,补肾生髓成肝法成为一种有前景的中医治疗方案.本文从理论渊源、临床研究、作用机制3个方面对此进行总结分析,以期为基于"肾生髓,髓生肝"理论指导治疗慢性肝衰竭的临床应用提供参考.

青蒿素(ARS)是临床上常用的抗疟药物,其陆续开发出了青蒿琥酯(ART)、双氢青蒿素(DHA)、蒿甲醚等多种青蒿素衍生物还可能对包括肝癌在内的多种癌症具有治疗意义.其中ART和DHA是青蒿素类药物中活性较强的衍生物,对人肝癌细胞有明显的抑制作用,而对非肿瘤正常肝细胞的毒性更低,且不易产生耐药性,具有成为治疗肝癌新药物的潜在性.

目的 探讨慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的危险因素.方法 选取2018年1月至2020年6月在杭州市西溪医院诊断治疗的慢性乙型肝炎患者130例的临床资料进行回顾性分析,130例患者中35例发生慢加急性肝衰竭,为肝衰组,95例为非肝衰组.记录患者的一般资料及临床资料,单因素及多因素分析慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的危险因素.结果 单因素分析结果显示,HBV DNA≥107拷贝/L,有家族史,合并感染,肝功能分级C级的患者发生肝衰竭的发生率更高,差异有统计学意义(P<0.001);肝衰竭组TBiL更高,清蛋白水平更低,国际标准化比率更高,凝血酶原活动度更低,与非肝衰组比较,差异有统计学意义(P<0.001).多因素分析结果显示,HBV DNA≥107拷贝/L,感染,肝功能分级C级,TBiL≥171μmol/L,国际标准化比率≥1.5是慢性乙型病毒性肝炎发生慢加急性肝衰竭的独立危险因素,PTA>40％,清蛋白>20 g/L是保护因素(P<0.001).结论 慢加急性肝衰竭是慢性乙型病毒性肝炎严重的并发症,患者预后较差.影响慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的因素较多,对于具有高危因素的患者,应积极预防慢加急性肝衰竭的发生.

目的 评价中药敷脐治疗难治性肝硬化腹水的疗效.方法 在中文数据库:中国知网、维普、万方数据库、中国生物医学文献数据库以及外文数据库:Cochrane?Library、EM-BASE、Pubmed中检索2009年1月至2021年8月发表的有关中药敷脐治疗难治性肝硬化腹水的文献,纳入中药敷脐联合西医综合治疗对比单纯西医综合治疗的随机对照试验(RCTs).结果 符合纳入标准的文献共8篇,对其中的随机对照试验进行荟萃分析,中药敷脐治疗与对照组比较,腹水缓解率更高(RR=1.49,95％CI:1.30～1.70,P<0.001),尿量增多(P<0.001),腹围变小(P<0.007),门静脉血流量减少(OR=-323.72,95％CI:-451.66～-195.79,P<0.001);而血清白蛋白两组差异无统计学意义(P>0.05).结论 中药敷脐治疗能促进腹水缓解,可能与增加24?h尿量、降低门静脉血流量有关,可能不引起血清白蛋白的改变.

肝衰竭是由多种因素(病毒、药物、酒精等)引起的严重肝脏损害,导致肝脏合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现以凝血功能障碍、黄疸、肝性脑病、腹水等为主要表现的一组临床症候群[1],现代医学尚缺乏特效药物和其他手段.本单位参与科技部传染病重大专项研究显示,中西医结合治疗肝衰竭可控制并发症,改善临床症状,提高治愈率[2].

目的 探讨牙周炎与肝硬化分期的相关性.方法 收集2019年6月至2020年12月在本院门诊或住院治疗的乙型肝炎肝硬化代偿期和失代偿期的患者各60例,另选取同期在本院体检的健康人群60例作为对照组,观察比较三组研究对象的牙周状况.结果 三组的牙周状况比较,差异有统计学意义(P<0.05).肝硬化患者的牙周状况差于健康对照人群(P<0.05).乙型肝炎肝硬化代偿期患者的牙周状况优于失代偿期患者(P<0.05).结论 乙型肝炎肝硬化患者的牙周状况可能与病情程度存在相互促进作用.

BackgroudThe outbreak of COVID-19 has brought unprecedented perils to human health and raised public health concerns in more than two hundred countries. Safe and effective treatment scheme is needed urgently.ObjectiveTo evaluate the effects of integratedTCM and western medicine treatment scheme on COVID-19.MethodsA single-armed clinical trial was carried out in Hangzhou Xixi Hospital, an affiliated hospital with Zhejiang Chinese Medical University. 102 confirmed cases were screened out from 725 suspected cases and 93 of them were treated with integrated TCM and western medicine treatment scheme.Results83 cases were cured, 5 cases deteriorated, and 5 cases withdrew from the study. No deaths were reported. The mean relief time of fever, cough, diarrhea, and fatigue were (4.78 ± 4.61) days, (7.22 ± 4.99) days, (5.28 ± 3.39) days, and (5.28 ± 3.39) days, respectively. It took (14.84 ± 5.50) days for SARS-CoV-2 by nucleic acid amplification-based testing to turn negative. Multivariable cox regression analysis revealed that age, BMI, PISCT, BPC, AST, CK, BS, and UPRO were independent risk factors for COVID-19 treatment.ConclusionOur study suggested that integrated TCM and western medicine treatment scheme was effective for COVID-19.

目的 探讨外周血微小RNA(miR)-146基因多态性与乙型肝炎病毒感染患者肝硬化的易感性及其水平与病情严重程度的关系.方法 选择杭州市西溪医院肝病科2018年5月-2020年6月收治的乙型肝炎肝硬化患者100例纳入研究组,选择同期医院收治的乙型肝炎非肝硬化患者60例作为对照组.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测两组miR-146a基因rs2910164位点基因型及表达水平,比较不同基因型患者乙型肝炎病毒载量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及总胆固醇(TC)水平.结果 研究组miR-146a基因rs2910164位点CC基因型、C等位基因频率均高于对照组(P＜0.05);100例慢性乙型肝炎肝硬化患者根据病情程度分为Child-pugh(A、B、C)三组,Child-pugh C组CC基因型频率高于Child-pugh A组及Child-pugh B组(x2=18.291、11.431,P均＜0.001);miR-146a基因rs2910164位点CC基因型患者miR-146 mRNA、AST、ALT、TC水平高于TT/TC患者(P＜0.05),HBV-DNA水平比较差异无统计学意义.结论 miR-146a基因rs2910164位点多态性与HBV感染者发生肝硬化风险相关,miR-146 mRNA水平对肝硬化程度判断具有一定的价值.

原发性胆汁性胆管炎(PBC)是一种以进行性、非化脓性、破坏性肝内小胆管炎为病理特点的慢性胆汁淤积性肝病.PBC的常见症状为瘙痒和乏力,此外,慢性胆汁淤积可引起高脂血症、骨病、脂溶性维生素缺乏等[1].该病由最初的胆管损伤逐步发展成肝纤维化、肝硬化,严重影响患者的生活质量.近年来,随着自身免疫性抗体检验技术的普及,本病的检出率逐年上升.但目前西医治疗该病的药物有限.熊去氧胆酸(UDCA)是治疗PBC的一线用药,可以改善本病患者的生化指标、延缓组织学进展、延长无肝移植生存期.但是,临床有大约1/3的PBC患者对UDCA反应不完全[2,3].国外研究报道奥贝胆酸、贝特类药物治疗PBC具有一定的疗效,但仍需更长时间和更大规模的研究来评估,目前国内尚未推广[4-6].多项研究显示中医药配合UDCA治疗本病具有协同作用,中医药治疗PBC具有较好的疗效,展现出了较好的前景,现从其病因病机、针对核心病机的中医治疗等方面进行论述.

目的:构建可用于预测乙型肝炎病毒相关慢加急性肝衰竭患者结局的风险模型.方法:以国家"十二五"科技重大专项课题"慢加急性肝衰竭中西医结合治疗方案优化研究"入组的乙型肝炎病毒相关慢加急性肝衰竭患者为研究对象,按照2:1分为训练集、测试集.在训练集人群中建立死亡风险模型并通过Cox回归分析,在测试集中验证模型的区分度与一致性.结果:年龄(HR=1.02,95％CI 1.01～1.04)、总胆红素(HR=1.04,95％CI 1.02～1.07)、国际标准化比值(HR=2.58,95％CI 1.98～3.37)、肝性脑病(Ⅰ/Ⅱ期:HR=2.20,95％CI 1.25～3.87;Ⅲ/Ⅳ期:HR=23.67,95％CI 7.74～72.37)、肝肾综合征(HR=3.64,95％CI 1.69～7.82)、低钠血症(HR=1.86,95％CI 1.22～2.84)、血小板计数(20～60:HR=1.42,95％CI 1.89～2.27;>60:HR=2.42,95％CI 1.94～6.20)是预后的独立影响因素;基于上述7项因素建立的列线图可以准确预测乙型肝炎病毒相关慢加急性肝衰竭人群结局;列线图在预测28、336 d结局方面优于终末期肝病模型(MELD)及MELD-Na评分(0.87 vs 0.79/0.80,0.82 vs 0.73/0.75);在预测90 d结局时优于MELD评分(0.86 vs 0.79,P=0.042),但与MELD-Na评分差异无统计学意义(0.86 vs 0.82,P=0.140).结论:以年龄、总胆红素、国际标准化比值、肝性脑病、肝肾综合征、低钠血症、血小板计数等7个关键因素构建而成的列线图,在预测乙型肝炎病毒相关慢加急性肝衰竭患者死亡风险方面具有一定的价值.

目的:分析湿热瘀黄证慢加急性肝衰竭患者肠道菌群分布特征,探讨其在预测慢加急性肝衰竭预后中的价值.方法:纳入湿热瘀黄证慢加急性肝衰竭患者37例,提取粪便肠道菌群DNA,进行16S rDNA高通量测序,以入组24周时状况或死亡为终点判断,分为好转组和无好转组,应用生物信息分析软件和统计学软件对测序结果进行分析.结果:好转组患者厚壁菌门、芽孢杆菌纲、丹毒丝菌纲、乳杆菌目、巴斯德菌科、十八梭菌属的相对丰度高于无好转组(P<0.05),而变形菌门、肠杆菌目的相对丰度低于无好转组(P<0.05);两组间Alpha多样性分析没有明显差异;好转组患者肠道菌群物种数量大于无好转组;Lefse分析显示两组患者肠道菌群在多个分类学水平都有比较大的差异(P<0.05).结论:湿热瘀黄证慢加急性肝衰竭患者病情进展与其肠道菌群有着密切联系,肠道菌群在预测病情转归及预后方面有着重要的价值.

Cardio-cerebrovascular disease (CCVD) is a major comorbidity of coronavirus disease 2019 (COVID-19). However, the clinical characteristics and outcomes remain unclear. In this study, 102 cases of COVID-19 from January 22, 2020 to March 26, 2020 in Xixi Hospital of Hangzhou were included. Twenty cases had pre-existing CCVD. Results showed that compared with non-CCVD patients, those with CCVD are more likely to develop severe disease (15% versus 1%), and the proportion of pneumonia severity index grade IV was significantly higher (25% versus 3.6%). Computed tomography images demonstrated that the proportion of multiple lobe lesion involvement was significantly higher in the CCVD group than in the non-CCVD group (90% versus 63.4%). Compared with non-CCVD group, the levels of C-reactive protein, fibrinogen, D-dimer, and serum amyloid-A were higher, whereas the total protein and arterial partial PaO2 were lower in the CCVD group. Although no statistical difference was observed in the outcomes between groups, CCVD patients received more intensive comprehensive treatment to improve COVID-19 symptoms compared with non-CCVD patients. Integrated Chinese and Western medicine treatments have certain advantages in controlling the severe conversion rate and mortality of COVID-19. In addition, given that COVID-19 patients are usually related to coagulation disorders and thrombosis risk, the application of Chinese medicine in promoting blood circulation and removing stasis should be strengthened.

自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)可加剧慢加急性肝衰竭并发肝功能损害,明显增加死亡风险,尽早诊断及预防SBP发生对降低慢加急性肝衰竭病死率有重要意义[1].越来越多的研究证实肠道菌群与肝脏疾病的发生发展存在密切联系,肠道微生态紊乱对肝衰竭病情进展也有一定影响,但尚待深入研究[2-4].本研究运用 16S rDNA高通量测序技术对慢加急性肝衰竭患者粪便菌群基因组进行分析,对比有无SBP患者肠道菌群在结构和功能上的异同,旨在探讨慢加急性肝衰竭患者并发SBP的肠道菌群特征,为提高SBP诊治能力并最终改善肝衰竭患者预后提供线索.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9–43.2%) in the experiment group and 27.21% (95% CI 22.0–32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4–12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

Background: Up to now, COVID-19 has infected more than 60 thousand of people in China and is gradually spread globally. The disease was named as Novel coronavirus pneumonia (NCP) on February 8th. We analyzed data on 60 confirmed cases in Hangzhou to determine the clinical characteristics of NCP with or without renal injury. Methods: In this cross-sectional, descriptive study, we collected clinical information on demographic characteristics, pulmonary high resolution computerized tomography (HRCT) imaging and other clinical indicators of NCP cases. Urine protein(Upro) was used to divided patients into the Upro positive group (Upro+ group) and the negative Upro group(Upro- group). Then difference of clinical indexes between the two groups and relationship between Upro and clinical indexes were analyzed. Findings: Among the 60 patients, Upro positive rate was 51.67%, and urine protein and urine erythrocyte co-positive rate was 11.67%. The level of blood lymphocyte, serum Age, married, BMI, history of hypertension, ALT, AST, Glb, Scr, LDH, lymphocyte, CRP and moderate pulmonary HRCT imaging of Upro+ group were remarkably severe than those of Upro- group (P < 0.05). Abnormal rates of AST and CRP were significantly higher in Upro+ group. The results of binary regression analysis showed that Scr (OR=1.1;), AST (OR=1.199), age (OR=1.1) and grade of pulmonary HRCT imaging (OR=0.315) were homodirectional impact factors and blood lymphocyte(OR=0.222) was the reverse impact factor of urine protein positive. Interpretation: High rate of Upro positive was detected in NCP patients, The degree of pulmonary lesion is positively related with level of Upro. Moreover, age, AST and lymphopenia were homodirectional impact factors with Upro. This study reminded us to pay more attention to the protective measures for lung, kidney and heart in the early stage of clinical treatment, and the mechanisms of how COVID-19 induced renal injury need to be future studied. Funding Statement: Zhejiang Natural Science Foundation Committee. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was approved by the Ethics Commission of Hangzhou Xixi Hospital affiliated to Zhejiang Chinese Medical University (2020- KLS-15).

杭州市西溪医院作为杭州市市属定点医院,承担了杭州市新型冠状病毒肺炎(下称"新冠肺炎")疫情的诊治工作.我院中医专家组特拟定西溪新冠3号方,用于治疗普通型新冠肺炎湿毒郁肺证患者,获效较好,现报道如下.

新型冠状病毒肺炎(COVID-19)是由新型冠状病毒感染所致,以发热、乏力、干咳为主要临床表现,传染性强,病因为感受疫疠之气,属于中医"疫病"的范畴,病位在肺脾,发病多与"寒、湿、热、毒、瘀"等多因素有关,但疾病不同时期的侧重点不同,故需分期而论,分证而治.本文将探讨中医药对杭州市新型冠状病毒肺炎患者的分期辨证治疗,充分挖掘中医药对新型冠状病毒肺炎的治疗潜力.