茵栀黄口服液联合硫普罗宁治疗药物性肝损伤的临床研究

目的探讨茵栀黄口服液联合注射用硫普罗宁治疗药物性肝损伤的临床疗效。方法选取2015年8月—2017年9月成都市新都区人民医院收治的药物性肝损伤患者100例为研究对象,根据随机区组设计法将患者分为对照组和治疗组,每组各50例。对照组静脉滴注注射用硫普罗宁,400 mg加入到5%葡萄糖注射液500 mL中,1次/d。治疗组在对照组基础上口服茵栀黄口服液,10 mL/次,3次/d。两组均连续治疗1个月。观察两组的临床疗效,比较两组的肝功能、临床症状和炎性因子。结果治疗后,对照组和治疗组的总有效率分别为72.0%、92.0%,两组比较差异具有统计学意义(P0.05)。治疗后,两组丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、总胆红素(TBIL)水平均显著下降,白蛋白(ALB)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些肝功能指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组腹胀、乏力、纳差、黄疸、肝脾大改善率均显著高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肿瘤坏死因子-α(TNF-α)、干扰素-γ(TNF-γ)水平显著降低,血清白细胞介素-10(IL-10)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些炎症因子的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论茵栀黄口服液联合注射用硫普罗宁治疗药物性肝损伤具有较好的临床疗效,可改善患者的肝功能和临床症状,降低炎性因子水平,具有一定的临床推广应用价值。     

Factors influencing lower extremity amputation outcomes in people with active foot ulceration in regional Australia: A retrospective cohort study

Australia has the second highest rate of non-traumatic lower extremity amputation (LEA) globally. Australia's large geographical size is one of the biggest challenges facing limb preservation services and may be contributing to LEA. The aim of this study was to determine what factors contribute to the likelihood of LEA in people with active foot ulceration in regional Australia. This retrospective cohort study audited patients with active foot ulceration in a multidisciplinary high risk foot service (HRFS) in regional Australia. Neurological, vascular and wound characteristics were systematically extracted, along with demographic information. Participants were followed for at least 12 months until healing or LEA occurred. Correlations between LEA and clinical and demographic characteristics were assessed using the Pearson's product moment correlation coefficient and chi squared test for independence. Significant variables (p < 0.05) were included in the model. Direct logistic regression assessed the independent contribution of significantly correlated variables on the likelihood of LEA. Of note, 1876 records were hand screened with 476 participants (25%) meeting the inclusion criteria. Geographical distance from the HRFS, toe systolic pressure (TSP), diabetes and infection were all significantly correlated with LEA and included in the logistic regression model. TSP decrease of 1 mmHg (OR 1.02, 95% CI 1.01–1.03), increased geographical distance (1 km) from HRFS (OR 1.006, 95% CI 1.001–1.01) infection (OR 2.08, 95% CI 1.06–4.07) and presence of diabetes (OR 3.77, 95% CI 1.12–12.65) were all significantly associated with increased likelihood of LEA. HRFS should account for the disparity in outcomes between patients living in close proximity to their service, compared to those in rural areas. Optimal management of diabetes, vascular perfusion and control of infection may also contribute to preventing LEA in people with active foot ulceration.     

大鼠应激性溃疡发病机制及其防治方法的研究

为进一步了解应激性溃疡的发病机制，寻找更有效的治疗方法。以冷束缚法制成大鼠应激性溃疡动物模型。将其分成对照组、治疗Ａ组（西米替丁组）、治疗Ｂ组（东莨菪碱组）和治疗Ｃ组（西米替丁＋东莨菪碱组），通过溃疡指教、光镜与电镜观察各组病理组织学变化。结果：治疗Ｃ组防治效果优于治疗Ａ组及Ｂ组。作者认为：在应激状态下，胃粘膜局部血循环障碍与胃内ｐＨ过低是导致损伤的重要始动因素；综合使用抑酸与促进血循环的防治方法，其效果明显优于单纯抑酸方法。     

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.     

Value of laboratory investigations in clinical suspicion of cytomegalovirus-induced upper gastrointestinal tract ulcerations in HIV-infected patients

To assess the value of laboratory investigations for the diagnosis and treatment of cytomegalovirus-induced upper gastrointestinal tract ulcerations, the medical records and biopsy material from HIV-infected patients were reviewed retrospectively during a 12-month period. Clinical diagnosis of cytomegalovirus (CMV) ulceration, based on characteristic endoscopic appearance of extensive ulceration of the mid- to distal esophageal or gastric mucosa and responsiveness to anti-CMV therapy, was compared with laboratory investigations of biopsies. Laboratory procedures consisted of both histopathological examination of the biopsy specimens and viral culture. Twenty episodes in 12 HIV-infected patients could be evaluated. Clinical diagnosis of CMV ulceration appeared to be justified in 14 of 20 episodes (70%), which were confirmed by laboratory investigations. Of the remaining six episodes, which showed partial or no response to anti-CMV therapy, laboratory investigations were negative in two episodes and discrepant in four episodes (histopathology or viral culture positive). A good response to anti-CMV therapy was more frequent in patients whose biopsies proved positive by histopathological examination and/or viral culture than in patients with negative tests (82% versus 0%), which indicates the importance of both investigations. In conclusion, laboratory diagnosis of CMV-induced upper gastrointestinal tract ulcerations supported the diagnosis and decisions on treatment of CMV-induced upper gastrointestinal tract ulcerations. © 1996 Wiley-Liss, Inc.     

Drug-induced liver injury by glecaprevir/pibrentasvir treatment for chronic hepatitis C infection: a systematic review and meta-analysis

Background: Glecaprevir/pibrentasvir (G/P; 300 mg/120 mg) is a new direct-acting antiviral (DAA) that exhibits anti-hepatitis C virus (HCV) pan-genotype (GT) activity for 8, 12, or 16 weeks. However, the U.S. Food and Drug Administration have received reports that using G/P causes moderate to severe liver impairment. In some cases, isolated hyperbilirubinemia and jaundice have been reported without concomitant evidence of increased transaminase levels or other hepatic decompensation events. Objective: This study aimed to analyze the incidence of drug-induced liver injury of G/P for chronic hepatitis C virus.Materials and methods: We searched databases from the inception of each database until March 2021. Data were pooled using a random-effects model. The Cochrane Risk of Bias Tool (RoB 2.0) and the OpenMeta [Analyst] software were performed for quality assessment and quantitative studies, respectively. The primary outcome was grade 3 level of drug-induced liver injury (DILI). Results: The nine studies included in the meta-analysis involved a total of 7,650 participants, and the overall sustained virologic response rate was above 95%. The most frequent drug-related laboratory abnormalities in DILI involved total bilirubin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin, but these abnormalities were minimal. The cirrhosis–without cirrhosis incidence risk ratio (IRR) was 2.724 (95% confidence interval: 1.182–6.276) in the grade 3 hyperbilirubinemia subgroup analysis. No significant differences were found within the other subgroups, in HCV GTs, and in treatment duration.Conclusions: DILI was found to occur frequently with G/P treatment. Hyperbilirubinemia occurred most frequently, especially, in patients with cirrhosis. However, G/P is still the primary therapy of choice for CKD and end-stage renal disease (ESRD) patients due to a superior safety rate.     

临床药师参与1例儿童药物超敏反应综合征的药学监护实践

目的 探讨万古霉素致药物超敏反应综合征的药学监护要点。方法 临床药师对1例万古霉素致药物超敏反应综合征儿童实施药学监护,调整患儿用药方案,监测抗菌药物血药浓度并调整给药剂量,并进行相关文献分析。结果 经过早期识别并停用可疑致敏药物后,患儿经对症支持治疗后病情好转出院。 结论 儿童药物超敏反应综合征患者具有儿童的特殊性,临床医师与临床药师应重点关注特殊人群的用药安全,做到早发现、早治疗。     

An unusual pattern of peritubular capillary injury involving apoptosis in a renal transplant patient

Microvascular injury is an important factor in renal allograft survival. Repeated episodes of endothelial injury from chronic antibody-mediated rejection typically manifest at the ultrastructural level as circumferential multilayering of remodeled glomerular basement membrane material and peritubular capillary basal lamina. In contrast to this typical pattern of microvascular injury, a renal transplantation case is presented in which focally dilated and multilayered segments of peritubular capillary basal lamina bearing lipid droplets were interspersed with ultrastructurally normal unilayered segments of basal lamina devoid of lipid droplets. Glomerular basement membranes were not affected by this process. The peak incidence of lipid droplets within the peritubular capillary walls coincided with a peak in apoptotic activity within the allograft. Lesser amounts of the same lipidic material were identified in the mesangial matrix and an arteriolar wall. Mesangial electron-dense deposits were detected at two weeks posttransplantation and their appearance coincided with elevated immunological activity in the glomeruli, as determined by immunofluorescence microscopy. The unusual ultrastructure and immunological activity observed in this case may reflect a process of impaired apoptotic clearance within the allograft. The six biopsies from a single patient are discussed in the setting of a highly sensitized renal transplant recipient who received prophylactic terminal complement blockade by eculizumab. The findings may be relevant to the study of apoptosis, efferocytosis, microvascular injury, eculizumab, rejection, lupus, and drug-related disease.     

Riga‐Fede disease in the upper jaw in an infant

Riga‐Fede disease is a benign and uncommon mucosal disorder. This illness is an ulceration of the oral mucosa and arises from repetitive traumatic injuries. The disease is usually caused by the sharp edges of new erupted teeth. The aim of the present case report is to present Riga‐Fede disease and its treatment. We reported a 11‐month‐old healthy female infant diagnosed as Riga‐Fede disease based on clinical features. After the conservative treatment that focused on eliminating the source of trauma, total healing was observed. Riga‐Fede disease is rare. This illness can be confused with malignancies. Therefore, the diagnosis and treatment of this disease are very important for physicians and patients.     

间接型药物性肝损伤:新类型与新挑战

间接型药物性肝损伤是由药物的治疗作用所引起的肝损伤,而不是因为药物固有的肝毒性或免疫原性所导致的一类新型药物性肝损伤(DILI)。目前临床常见的间接型DILI主要有3种临床表型,即免疫检测点抑制剂相关肝损伤、药物引起肝炎病毒再激活和药物影响肝细胞代谢所致的脂肪肝或原有脂肪肝加重。由于间接型DILI是一类新型DILI,临床对其认识不足,诊治经验缺乏。尤其是随着免疫检测点抑制剂在临床快速推广应用,间接型DILI迅速增加,给临床诊断和治疗带来更大的挑战。因此,对间接型DILI常见类型的临床特点、发病机制及诊断治疗等研究进展等进行综述,具有重要的临床意义。