500 Cases of High-intensity Focused Ultrasound (HIFU) Ablated Uterine Fibroids and Adenomyosis

ObjectiveClinical outcomes of 500 high-intensity focused ultrasound (HIFU)-treated uterine fibroids and adenomyosis are analyzed and presented.Materials and methodsThis is a retrospective cross-sectional analysis from a single tertiary medical center. From April 2015 to October 2018, 546 cases were enrolled for the study. After excluding 46 patients with less than 3 months of follow-up period, there were 404 fibroids, 149 adenomyosis and 53 mixed conditions entered for analysis. The patients’ uterine fibroids and adenomyosis were treated by HIFU according to Chongqing Haifu protocol, with 12 cm diameter transducer of focal length 10–16  cm at 0.8 or 1.6 MHz T2-weight MRI imaging was rendered prior to and 3 month post treatment to assess lesion volume change using non-perfusion volume, which was the primary outcome. Secondary outcomes including quality of life, subjective satisfaction, adverse events and pregnancy rate were determined using self-reported questionnaires. The mean follow up period ranged from 3 to 38 months with an average of 21 months.ResultsThree months after HIFU-treated uterine fibroids and adenomyosis, the lesion size reduced 40.2% and 46.3%, respectively. Symptoms all improved with better quality of life for the fibroid group, while those with adenomyosis or combined diseases benefit the most from pain control. Serum CA125 decreased significantly for all studied groups, and LDH only showed improvement for fibroids group. Number of adverse events is comparable to Chongqing data (approximately 10.2%), with mostly mild and self-resolving conditions. No permanent sequelae or death was documented. Twelve pregnancies are reported in this cohort.ConclusionHIFU is safe and effective in treating uterine fibroids and adenomyosis. The results are reproducible if standardized treatment schedules are followed. It is a promising treatment alternative with the advantages of precision, non-invasiveness, rapid recovery and readiness for pregnancy.     

直接抗病毒药物治疗丙型肝炎合并透析患者的临床应用

丙型肝炎病毒（HCV）感染在慢性肾功能不全患者中较常见，尤其是在进行透析的患者中，HCV感染较普通患者的风险极大增加，同时还会导致肝细胞癌及肝硬化的发病率明显升高。近年来直接抗病毒药物（DAAs）在慢性丙型肝炎的治疗中取得了较好的疗效及安全性，本文通过总结DAAs在丙型肝炎合并透析患者中的应用进展，发现对于基因1~6型HCV合并透析患者，推荐使用G/P方案；由于索磷布韦（SOF）经肾脏代谢，在重度肾损害人群中的血药浓度较高，因此SOF组合方案并不推荐用于丙型肝炎合并透析患者的治疗。     

Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Association between de novo lipogenesis susceptibility genes and coronary artery disease

Background and aimsCoronary artery disease (CAD) is the principal cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to use genetic epidemiology to study the association between de novo lipogenesis (DNL), one of the major pathways leading to NAFLD, and CAD risk.Methods and resultsDNL susceptibility genes were used as instruments and selected using three approaches: 1) genes that are associated with both high serum triglycerides and low sex hormone-binding globulin, both downstream consequences of DNL (unbiased approach), 2) genes that have a known role in DNL (biased approach), and 3) genes that have been associated with serum fatty acids, used as a proxy of DNL. Gene-CAD effect estimates were retrieved from the meta-analysis of CARDIoGRAM and the UK Biobank (～76014 cases and ～264785 controls). Effect estimates were clustered using a fixed-effects meta-analysis. Twenty-two DNL susceptibility genes were identified by the unbiased approach, nine genes by the biased approach and seven genes were associated with plasma fatty acids. Clustering of genes selected in the unbiased and biased approach showed a statistically significant association with CAD (OR:1.016, 95%CI:1.012; 1.020 and OR:1.013, 95%CI:1.007; 1.020, respectively), while clustering of fatty acid genes did not (OR:1.004, 95%CI:0.996–1.011). Subsequent exclusion of potential influential outliers did reveal a statistically significant association (OR:1.009, 95%CI:1.000; 1.018).ConclusionsDNL susceptibility genes are associated with an increased risk of CAD. These findings suggest that DNL may be involved in the pathogenesis of CAD and favor further development of strategies that target NAFLD through DNL.     

帕拉米韦注射液治疗儿童流感的临床疗效分析

目的探讨儿童流感应用帕拉米韦注射液治疗的临床疗效以及用药安全性。方法随机选定在2016年1月-2019年1月期间佛山市高明区人民医院儿科住院治疗并确诊流感A或B型患儿200例,通过随机数字法将其分为治疗组和对照组。治疗组100例用帕拉米韦注射液治疗,对照组100例用国产磷酸奥司他韦颗粒治疗,评价两组患儿治疗前后症状评分、治疗效果、治疗指标以及不良反应发生情况。结果两组患儿治疗前流感样症状评分无统计学意义(P>0.05),两组患儿治疗后较治疗前流感样症状评分均下降,差异有统计学意义(P<0.05);治疗组治疗后流感样症状评分略小于对照组,但是无统计学意义(P>0.05);治疗组治疗总有效率高于对照组,治疗组患儿发热症状缓解、全部症状缓解以及住院时间均小于对照组,存在统计学意义(P<0.05)。治疗组与对照组不良反应发生率较低,且无统计学意义(P>0.05)。结论帕拉米韦注射液可用于儿童流感治疗,不仅能够保证临床疗效,而且可加快症状缓解,同时存在较高用药安全性。     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study

IntroductionAlthough peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia.MethodsThis retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors.ResultsOne hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the β-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489–1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399–1.876; P = 0.71).ConclusionsPeak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.