基于网络药理学及分子对接预测安子调冲方中和血中药对免疫相关复发性流产的作用机制

目的：应用网络药理学及分子对接技术探讨安子调冲方（ATF）中起和血作用的鸡血藤–蒲黄炭（JXT–PHT对治疗免疫相关复发性流产（IRRPL）的作用机制,为进一步对ATF的拆方研究奠定基础。方法：利用TCMSP和HERB数据库进行化合物成分检索,在Swiss Target Prediction数据库预测药物作用靶点。使用Genecards和ImmPort数据库获取IRRPL相关靶点。利用jvenn绘制韦恩图,得到潜在作用靶点。在STRING数据库构建蛋白互作（PPI）网络,并分析关键作用靶点。构建“和血作用中药–成分–靶点–疾病”网络,在Cytoscape 3.10.0中可视化,并分析核心成分。应用DAVID(v2023q1)数据库,对潜在作用靶点进行基因本体（GO）和京都基因和基因组数据库（KEGG）功能富集分析。最后通过AutoDock–Vina(v1.2.5)对关键作用靶点和核心成分执行分子对接,在PyMOL 2.5进行可视化。结果：共筛选出ATF中起和血作用的JXT–PHT 31个活性成分,预测靶点586个,IRRPL相关靶点226个,潜在作用靶点38个,构建PPI网络并分析后得...     

小儿再发性腹痛的病因学分析

目的 分析小儿再发性腹痛的病因以及相关的因素为临床选择辅助检查及诊断提供依据或参考。方法 268例再发性腹痛患儿选人调查对象,对其进行病因学调查,调查内容包括年龄、性别、季节、诱因、部位等8个因素,进行分析。选择相关的辅助检查确定病因。结果 有52例有器质性疾病(19．4％),以慢性胃炎居首位。与发作有关的因素有季节、年龄、情绪反应。结论 小儿再发性腹痛绝大多数属于功能性疾病,只有少数由器质性原因引起,但仍应引起足够重视,谨慎的选择辅助检查,避免漏诊。     

Elevated sperm DNA fragmentation does not predict recurrent implantation failure

In this study, we sought to determine whether sperm DNA fragmentation (DFI%) and high DNA stainability (HDS%) evaluated by sperm chromatin structure assay (SCSA) predict recurrent implantation failure (RIF) or pregnancy rate. A retrospective study was performed of consecutive cycles of ICSI treatment from 2009 to 2018. A total of 386 couples that underwent 1,216 frozen embryo transfer (FET) cycles were analysed. Mean female and male age was 34 ± 3.6 years and 37.3 ± 6.6 years, respectively, and a median total motile sperm count (TMSC) was 43.5 [9.9–105.5] million. Overall median DFI% and HDS% was 12 [7.1–18.9] and 9.6 [6.5–14.4] respectively. On multivariable analysis, DFI% and HDS% were not associated with RIF (DFI%: OR = 1.01, 95% CI: 0.98–1.04, p = .414; HDS%: OR = 0.97, 95% CI: 0.94–1.01, p = .107) or IVF success, defined as clinical pregnancy (DFI%: OR = 1.00, 95% CI: 0.99–1.01, p = .641; HDS%: OR = 1.01, 95% CI: 0.99–1.02, p = .565). We found that neither DFI% or HDS%, as assessed by SCSA, were predictive of RIF or pregnancy rate. This finding suggests that sperm DNA fragmentation does not predict RIF or pregnancy rate.     

Flexor Tenosynovectomy for Recurrent Carpal Tunnel Syndrome: A Retrospective Case Series of 108 Hands

Background: The etiology of recurrent carpal tunnel syndrome (CTS) is unclear, and outcomes following secondary surgery in this demographic have been poorer than primary surgery. Fibrosis and hypertrophy have been identified in the flexor tenosynovium in these patients. The authors use flexor tenosynovectomy (FTS) for recurrent CTS after primary carpal tunnel release and present a review of these patients. Methods: A retrospective chart review was performed of 108 cases of FTS for recurrent CTS from 1995 to 2015 by 4 attending surgeons at one institution. Demographic information, symptoms, and outcomes were among the data recorded. A phone survey was conducted on available patients where the shortened version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and satisfaction were assessed. Results: Average office follow-up was 12 months. Average age was 57.5 years. A total of 104 (96%) reported symptom improvement and 48 (44%) reported complete symptom resolution. Forty patients were available for long-term follow-up at an average 6.75 years postoperatively via phone interview. Average QuickDASH score was 31.2 in these patients. Thirty-six (90%) of 40 patients were initially satisfied at last office visit, and 31 (78%) of 40 were satisfied at average 6.9 years, a maintenance of satisfaction of 86%. Satisfied patients were older (58 years) than unsatisfied patients (51 years). Conclusion: Both long-term satisfaction and QuickDASH scores in our cohort are consistent with or better than published results from nerve-shielding procedures. The authors believe a decrease in both carpal tunnel volume and potential adhesions of fibrotic or inflammatory synovium contributes to the benefits of this procedure. This remains our procedure of choice for recurrent CTS.     

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre– or post–liver transplant

Direct-acting antiviral (DAA) therapy has transformed the management of human immunodeficiency virus (HIV) and hepatitis C (HCV) coinfected patients with advanced liver disease. STOP-Coinfection was a multicenter prospective and retrospective, open-label study using sofosbuvir-based DAA therapy to treat HIV/HCV-coinfected participants pre– or post–liver transplant (LT). Sixty-eight participants with end-stage liver disease (Child-Turcotte-Pugh score ≥7 and Model for End-Stage Liver Disease score 6–29) were enrolled, 26 had hepatocellular carcinoma. Forty-two participants were treated pre–LT and 26 post–LT. All participants completed therapy without need for dose reduction or transfusion; eight required two or more courses of therapy. Ninety-three percent achieved a sustained virologic response and DAA therapy was well tolerated. Despite HCV cure, 12 end-stage liver disease participants required subsequent LT, 7 for decompensated liver disease. Thirteen participants died, 10 with decompensated liver disease pre–LT and three post–LT. Overall, transplant free survival was 42.8% at 4 years and post–LT survival was 87.9% at 5 years. We conclude that sofosbuvir-based DAA therapy is safe and highly effective in HCV-HIV patients with decompensated liver disease and post–LT, with post–LT survival rates comparable to other indications. This removes one of the last barriers to liver transplantation in this challenging cohort of recipients.     

Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss

Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.     

Epidemiology and virulence gene expression of intracellular group A streptococci in tonsils of recurrently infected adults

Intracellularly persistent group A streptococci (GAS, Streptococcus pyogenes) have been associated with recurrent tonsillopharyngitis and antibiotic treatment failure. As a supplementation of the published in vitro data, conventional bacteriology and molecular epidemiology was performed on material from 29 adult patients of a German army hospital with anamnestic signs of recurrent tonsillopharyngitis. Pre-surgery tonsil swabs and the surgically removed tonsils were examined with respect to growth of aerobic bacteria in absence and presence of antibiotics with exclusively extracellular activity. Under such antibiotic selection, Staphylococcus aureus and GAS were cultured from specimens of 13 and 3 patients, respectively. In every material GAS-positive by culture methods, the intracellular location of the penicillin-susceptible GAS isolates was confirmed by immunohistologic examination of tonsillar sections using a GAS-specific IgG antibody. The three intracellular GAS isolates were typed by emm gene sequencing and could be associated to types M6 and M49 (two isolates). The bacteria were serially passaged on sheep blood agar, and semiquantitative mRNA analysis from virulence genes was performed using bacteria of the 4th and 25th passage after isolation. An M-type-specific pattern of virulence gene expression and different gene expression levels in relation to the passage number were observed.     

Factor V Leiden and recurrent miscarriage-prospective outcome of untreated pregnancies

BACKGROUND: Some cases of recurrent miscarriage and later pregnancy complications have a thrombotic basis. Factor V Leiden is a common thrombophilic mutation. METHODS: The prospective outcome of untreated pregnancies amongst 25 women heterozygous for the Factor V Leiden allele who had a history of either recurrent early miscarriages only (three or more miscarriages at <12 weeks gestation; n = 19) or of late miscarriage (>12 weeks gestation; n = 9) was studied. Control groups of women with a similar pregnancy history but who had a normal Factor V genotype were also studied. RESULTS: The live birth rate was significantly lower amongst women with a history of recurrent early miscarriage who carried the Factor V Leiden allele (6/16; 37.5%) compared with that amongst those with a normal Factor V genotype (106/153; 69.3%; odds ratio 3.75, 95% confidence intervals 1.3-10.9). The live birth rate was 11.1% (1/9) amongst those with a history of late miscarriage carrying the Factor V Leiden allele and 48.9% (22/45) amongst those with a normal Factor V genotype. CONCLUSIONS: Attention should be directed at screening women with recurrent miscarriage associated with placental thrombosis for Factor V Leiden and a policy of targeted thromboprophylaxis during future pregnancies should be assessed in the form of a randomized controlled trial.     

Aberrant gene expression associated with recurrent pregnancy loss

Recent studies indicate that a number of factors including chromosomal abnormalities, immunological feto-maternal rejection, hormonal irregulation and anatomical factors are involved in provoking recurrent pregnancy loss (RPL). This indicates that normal cellular regulation of these factors is required for maintaining normal pregnancy. In addition, it is expected that biological processes for maintaining normal pregnancy require a series of differential gene expression. As expected, our previous investigations revealed that there are >/=30 genes showing different levels of expression between normal and RPL patients. In addition, other research groups have also identified a number of genes that are expressed aberrantly in pregnancy failure. In this review, recent study on aberrant expression levels of genes, which are grouped as immunity-related, angiogenesis-related, apoptosis-related and other groups of genes, will be discussed.