Combined 5‐hydroxymethylcytosine content of human leucocyte antigen‐B and human leucocyte antigen‐DQB1 as novel biomarker for anti‐tuberculosis drug‐induced liver injury

This study investigated the diagnostic value of 5‐methylcytosine (5‐mC) and 5‐hydroxymethylcytosine (5‐hmC) contents of human leucocyte antigen (HLA)‐B and HLA‐DQB1 in anti‐tuberculosis drug‐induced liver injury (ADLI). In total, 110 ADLI patients and 120 patients without ADLI controls were enrolled. Enzyme‐linked immunosorbent assay (ELISA) was used to detect the 5‐mC and 5‐hmC content in DNA from peripheral blood leucocytes. The univariate analysis showed that smoking, drinking, and 5‐mC and 5‐hmC content of HLA‐B and HLA‐DQB1 were significantly associated with ADLI. After adjusting for drinking and smoking, we found that 5‐mC content of HLA‐B and HLA‐DQB1 were associated with ADLI (odds ratio [OR] = 0.251 and 0.347, respectively) and 5‐hmC contents of HLA‐B and HLA‐DQB1 were also associated with ADLI (OR = 1.848 and 4.705, respectively). Receiver operating characteristic (ROC) analysis indicated that the 5‐hmC contents of both HLA‐B and HLA‐DQB1 were more clinically significant than the 5‐mC contents were. The combined 5‐hmC level of HLA‐B and HLA‐DQB1 was the best diagnostic biomarker for ADLI, with the highest areas under the curve (AUC) for 0.953, sensitivity for 0.900 and specificity for 0.875. Therefore, combined 5‐hmC levels of HLA‐B and HLA‐DQB1 could be significant evidence for diagnosis of ADLI.     

Antitumour properties based on the self‐assembly of camptothecin and carbamoylmannose conjugates

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self‐assembly based on camptothecin and carbamoylmannose conjugates ( CPT‐Man ) was constructed. The self‐assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT‐Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate‐modified antitumour properties by self‐assembled CPT drugs.     

中药注射剂用于新型冠状病毒肺炎患者的药学监护探讨

新型冠状病毒肺炎的爆发严重危害了人们的身体健康和生命安全。国家卫生健康委员会发布的《新型冠状病毒肺炎诊疗方案(试行第七版)》(以下简称第七版方案)中,推荐临床治疗期重型、危重型患者在使用中药饮片的同时可联合使用中药注射剂。本文针对第七版方案中推荐的部分中药注射剂,详细分析其相关作用特点及药学监护点,帮助临床医护人员合理使用中药注射剂,以利于中医药防治新型冠状病毒肺炎疫情,促进临床一线合理用药。     

Two novel SASH1 mutations in Chinese families with dyschromatosis universalis hereditaria

BackgroundDyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper‐ and hypo‐pigmented macules on the face, trunk, and extremities. The condition causes severe cosmetic problem which can lead to significant psychological distress to the patients and bear a negative impact on society. DUH is a condition with genetic heterogeneity. The SASH1 gene was recently identified as pathogenic genes in DUH patients.MethodsTwo families clinically diagnosed with dyschromatosis universalis hereditaria were enrolled. Whole‐exome sequencing combined with Sanger sequencing and bioinformatics analysis was performed in the probands. MutationTaster, CADD, SIFT, PolyPhen‐2, and LRT software, and The American College of Medical Genetics and Genomics Standards and Guidelines were employed to assess the pathogenicity of detected missense mutations. One hundred healthy unrelated Chinese individuals were used as controls. All participants signed an informed consent form.ResultsGenetic screening revealed a heterozygous SASH1 c.1547G>A (p.Ser516Asn) mutation for patients in family 1, and SASH1 c.1547G>T (p.Ser516Ile) for family 2. Both such de novo mutations are located in a highly conserved SLY domain in SASH1, have not been previously reported in any publication, and were not detected in any control databases.ConclusionsThe novel heterozygous mutations, SASH1 c.1547G>A and c.1547G>T, are likely responsible for the DUH phenotype in these two families. Our study expands the mutation spectrum of DUH. Whole‐exome sequencing showed its efficiency in the diagnostic of hereditary skin disorders.     

CRISPR/Cas9-based functional characterization of the pigmentation gene ebony in Plutella xylostella

Body pigmentation is an important character of insects in adapting to biotic and abiotic environmental challenges. Additionally, based on the relative ease of screening, several genes involved in insect melanization have been used in classic genetic studies or as visual markers in constructing transgenic insects. Here, a homologue of the Bombyx mori melanization-inhibiting gene ebony, associated with the conversion of dopamine to N-β-alanyl dopamine, was identified in a global pest, Plutella xylostella. The CRISPR/Cas9 system was applied to generate multiple Pxebony knockout alleles which were crossed to produce a Pxebony knockout strain, showing darker pigmentation in larvae, pupae and adults, compared with wildtype. Interestingly, we observed that Pxebony heterozygotes displayed an intermediate darkened phenotype, indicating partial dominance between the knockout and wildtype alleles. The fitness costs of Pxebony deficiency were also assessed in the mutant strain, indicating that embryo hatchability and larval survival were significantly reduced, while the eclosion rate was not obviously affected. Our work provides a potential target for exploring CRISPR-based genetics-control systems in this economically important pest lepidopteran.     

Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study

OBJECTIVEWe aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in the Chinese population.RESEARCH DESIGN AND METHODSThis study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan Study. All participants were monitored biennially until 31 December 2017. During follow-up, 11,384 participants were diagnosed as having type 2 diabetes. For each case subject, one control subject was randomly selected, matched for age (± 1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% CIs of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes versus control subjects across age-groups.ResultsDuring a median follow-up of 5.57 years, 1,794 incident events (907 CVD events, of which there were 725 strokes and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age <45 years had the highest relative risks of CVD and all-cause mortality relative to the matched control subjects, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age.CONCLUSIONSThe relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age-groups, and the associations were more evident in younger-onset type 2 diabetes.     

呼吸科住院患者抗生素药物相关腹泻风险预测模型的构建及验证

目的 通过分析呼吸科住院患者抗生素药物相关腹泻的危险因素,建立并验证呼吸科住院患者抗生素药物相关腹泻风险的列线图模型。 方法 纳入2019年1月—9月于北京市某三级甲等医院呼吸科病房住院使用抗生素治疗的患者291例并收集临床资料。应用Logistic回归模型分析呼吸科住院患者抗生素药物相关腹泻的独立危险因素。应用R软件构建预测呼吸科住院患者抗生素药物相关腹泻风险的列线图模型,并进行验证。 结果 Logistic回归分析显示,大便潜血[OR=4.517,95%CI（1.440~14.163）]、体重指数[OR=0.834,95%CI（0.735~0.947）]、血红蛋白浓度[OR=0.970,95%CI（0.946~0.994）]、院前使用抗生素[OR=2.957,95%CI（1.076~8.130）]及使用抗生素种类[OR=2.148,95%CI（1.146~4.026）]是呼吸科住院患者抗生素药物相关腹泻的独立危险因素（P<0.05）。对列线图模型进行验证,ROC曲线显示该模型预测呼吸科住院患者抗生素药物相关腹泻的风险曲线下面积为0.779;校准曲线为斜率接近于1的直线,Hosmer-Lemeshow拟合优度检验（ χ²=1.413,P=0.994）均显示该模型能够较准确地预测呼吸科住院患者抗生素药物相关腹泻的风险。结论 该研究基于大便潜血、院前使用抗生素、体重指数、血红蛋白浓度、使用抗生素种类数这5项抗生素药物相关腹泻发生的独立危险因素,构建的列线图模型具有良好的区分度与准确度,可为临床个体化预测抗生素药物相关腹泻发生风险提供参考。     

Two cases of tuberculous retropharyngeal abscess in adults

Retropharyngeal abscess (RPA) is an acute or chronic deep neck tissue infection. Tuberculous RPA is chronic and extremely rare in adults. A 20-year-old female patient visited the local hospital due to cough and sputum. The sputum smear was positive for acid-fast staining, and lung computed tomography (CT) indicated pulmonary tuberculosis (TB). The patient received the standard regimen of isoniazid+rifampicin+pyrazinamide+ethambutol (HRZE) for 6 months. After HRZE, pulmonary symptoms improved, but some pharyngeal discomfort remained. In another case, a 25-year-old male patient was admitted to our hospital because of a mass on the left side of his neck. Lymph node TB was considered after a puncture biopsy. Lung CT showed no obvious abnormality. After HRZE for 5 months, the mass had progressively enlarged. Both patients underwent B-ultrasonography-guided puncture, and Xpert® MTB/RIF of the abscess was positive and rifampin-sensitive. Tuberculous RPA was diagnosed and treated with isoniazid+rifampicin (HR) for 12 months. After combination anti-TB therapy and surgical drainage, both patients fully recovered. Tuberculous RPA is rare in adults; because of pharyngeal symptoms or progressive enlargement of a neck mass with anti-TB treatment, clinicians need to suspect tuberculous RPA in adults, which is treated with anti-TB therapy and surgery.     

血清TGF-β1、IL-17水平与急性肾盂肾炎患者头孢噻肟钠治疗预后的相关性

目的 探讨血清转化生长因子β1(TGF-β1)、白细胞介素-17(IL-17)水平与急性肾盂肾炎患者头孢噻肟钠治疗预后的相关性。方法 选取2019年7月-2021年7月于我院采用孢噻肟钠治疗的急性肾盂肾炎患者60例,治疗2周后,观察患者预后情况并分为预后不良组与预后良好组,所有患者治疗前均接受血清TGF-β1、IL-17水平检测,分析血清TGF-β1、IL-17水平与急性肾盂肾炎患者头孢噻肟钠治疗预后的相关性。结果 60例急性肾盂肾炎患者头孢噻肟钠治疗预后不良8例(13.33%),预后良好52例(86.67%);经Logistic回归分析,结果显示,血清TGF-β1、IL-17水平与急性肾盂肾炎患者头孢噻污钠治疗预后不良相关(OR>1, P<0.05);绘制ROC曲线,结果显示,血清TGF-β1、IL-17水平单独及联合预测急性肾盂肾炎患者头孢噻肟钠治疗预后的AUC>0.8,具有一定预测价值,其中联合预测价值最高。结论 血清TGF-β1、IL-17水平与急性肾盂肾炎患者头孢噻肟钠治疗预后密切相关,临床可通过检测血清TGF-β1、IL-17水平预测急性肾盂肾炎患者预后情况。