Drug-induced liver injury:Is it somehow foreseeable?

The classic view on the pathogenesis of drug-induced liver injury is that the so-called parent compounds are made hepatotoxic by metabolism (formation of neosubstances that react abnormally), mainly by cytochromes P-450 (CYP), with further pathways, such as mitochondrial dysfunction and apoptosis, also playing a role. Risk factors for drug-induced liver injury include concomitant hepatic diseases, age and genetic polymorphisms of CYP. However, some susceptibility can today be predicted before drug administration, working on the common substrate, by phenotyping and genotyping studies and by taking in consideration patients' health status. Physicians should always think of this adverse effect in the absence of other clear hepatic disease. Ethical and legal problems towards operators in the health care system are always matters to consider.

P2X receptors: New players in cancer pain

Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2 X receptor are adenosine triphosphate(ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2 X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2 X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent findings linking P2 X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesisof cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2 X receptor blockers to alleviate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed.

Cholangiocytes and blood supply

胆汁的树的微脉管的供应，仙子胆管丛(PBP ) ，源自肝的动脉树枝和流动进肝窦状隙。PBP 的详细三维的研究被使用扫描电子执行了显微镜学脉管的腐蚀演员组(SEMvcc ) 技术。认为 PBP 在支持胆汁的上皮的能分泌、吸收性的功能起一个基本作用，他们在常态和病理的组织被探索。正常的肝证明 PBP 安排在 extra-附近 -- 并且肝内的胆汁的树。在小门道， PBP 被日益增多地继续了它显示出一个更复杂的脉管的网络的额外的肝的 PBP 的 capillaries 的单个层描绘。在普通的管结扎(BDL ) 以后，胆汁管和 PBP 增长的进步修正被观察。PBP 介绍在许多胆汁管附近安排的一个三维的网络并且作为容器的捆出现，由有典型圆网孔结构的同类的直径的 capillaries 镇静。PBP 网络从显得正常的正弦曲线网络是容易可区分的。在 BDL 期间考虑 PBP 的庞大的延期，脉管的内皮生长因素(VEGF ) 起的可能的作用被评估。VEGF -- A， VEGF-C 和他们的相关受体高度出现了在 BDL 老鼠的增殖的 cholangiocytes 积极的免疫。到象肝的动脉结扎一样的 BDL 老鼠的 anti-VEGF-A 或 anti-VEGF-C 抗体的管理导致了一个减少的胆汁管团。rVEGF 的管理 -- 到 BDL 肝的动脉的 A 绑扎老鼠阻止了 cholangiocyte 增长和 VEGF 的减少 -- 表情作为与 BDL 控制老鼠相比。这些数据处于 cholangiocyte 增长的条件建议胆汁的树的动脉的血供给的角色，例如它发生在长期的胆汁郁积期间。在另一方面， VEGF 作为在 cholangiocytes 和 PBP endothelial 之间的串音的一个工具起的作用建议 VEGF 版本和功能的那操作能为肝的动脉或胆汁的树的损坏描绘的人的病理学的条件代表治疗学的策略。

Estrogens and the pathophysiology of the biliary tree

有关不同纸巾上的雌激素效果的科学框架在最后十年期间极其膨胀了，当时雌激素受体(嗯) 子类型被识别。雌激素是不仅必要的因为雌性生殖系统，而且他们也包括心血管系统，骨头，大脑和肝在另外的纸巾控制基本功能。最近，在他们调制 cholangiocytes 的增生的和分泌活动的地方，雌激素被显示了指向胆汁的树，上皮细胞衬里胆汁管。由在两雌激素受体(ER-alpha ) 并且(上扮演嗯贝它) 子类型，并且由激活 genomic 或 non-genomic 小径，雌激素在生长因素和 cytokines 的复杂的环起一个关键作用，它调制 cholangiocytes 的增生的反应损坏。明确地，雌激素激活细胞内部的发信号的串联[英皇家空军之阶级最低之兵( 1/2 )(细胞外的调整家族 ases ( 1/2 )，PI3- kinase/AKT (phosphatidylinositol-3' kinase/AKT )]典型地代表象象生长因素( IGF1 )一样的胰岛素那样的生长因素，神经生长因素( NGF )和脉管的内皮生长因素( VEGF )，因此加强他们的行动。另外，雌激素在增殖的 cholangiocytes 刺激不同生长因素的分泌物。这评论明确地处理与雌激素处于正常、病理学的条件由调制 cholangiocyte 功能的角色和机制有关的最近的进展。

Arthroereisis in juvenile flexible flatfoot:Which device should we implant?A systematic review of literature published in the last 5 years

BACKGROUND Flexible flatfoot(FFF)is a very common condition in children,characterized by the loss of the medial arch and by an increase in the support base with valgus of the hindfoot.Arthroereisis(AR)procedures are widely performed corrective surgeries and are classified as subtalar AR and calcaneo-stop(CS).AIM We investigated the literature published in the last 5 years with the aim of providing an update on the evidence related to AR treatment in FFF patients.We report the principal findings of subtalar AR and CS procedures concerning clinical and radiological outcomes and complication rates in the general population,young athletes,and obese people according to material device.METHODS Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses,a systematic review of studies published in the past 5 years and included the PubMed and Science Direct databases was performed on May 6,2020.The research string used was(pediatric OR children OR Juvenile NOT adult)AND(flexible NOT rigid)AND(flat foot OR pes planus)AND(calcaneo-Stop OR arthroereisis OR subtalar extra-articular screw OR SESA OR subtalar arthroereisis OR endosinotarsal).The risk of bias assessment was performed using the Dutch checklist form for prognosis.RESULTS A total of 47 articles were found.Ultimately,after reading the full text and checking reference lists,we selected 17 articles that met the inclusion and exclusion criteria.A total of 1864 FFFs were identified.Eight studies concerned the subtalar AR(47.1%)and nine concerning CS(52.9%).The average age of patients at start of treatment was 11.8 years,the average follow-up of the studies was 71.9 mo(range 29.1-130).Globally,complications occurred in 153 of the 1864 FFF treated,with a rate of 8.2%.CONCLUSION Both AR procedures are valid surgical techniques for treating FFF.Surgeon experience,implant cost,and cosmetic correction are the most common considerations included in the orthopedic device decision-making process.In obese patients,the subtalar AR is not recommended.In adolescents who need to improve sports performance,the CS screw had better results compared with other implants.

Role of calcium in polycystic kidney disease:From signaling to pathology

Autosomal dominant polycystic kidney disease(ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1(PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2(PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum(ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.

Calcific left atrium:A rare consequence of endocarditis

Usually, cardiac calcifications are observed in aortic and mitral valves, atrio-ventricular plane, mitral annulus, coronary arteries, pericaridium(usually causing constrictive pericarditis) and cardiac masses. Calcifications of atrial walls are unusual findings that can be identified only using imaging with high spatial resolution, such as cardiac magnetic resonance and computed tomography. We report a case of a 43-year-old patient with no history of heart disease that underwent cardiac evaluation for mild dyspnoea. The echocardiogram showed a calcific aortic valve and a hyper-echogenic lesion located in atrio-ventricular plane. The patient was submitted to cardiac magnetic resonance and to computed tomography imaging to better characterize the localization of mass. The clinical features and location of calcified lesion suggest an infective aetiology causing an endocarditis involving the aortic valve, atrioventricular plane and left atrium. Although we haven't data to support a definite and clear diagnosis, the clinical features and location of the calcified lesion suggest an infective aetiology causing an endocarditis involving the aortic valve, atrio-ventricular plane and left atrium. The patient was followed for 12 mo both clinically and by electrocardiogram and echocardiography without worsening of clinical, electrocardiographic and echocardiographic data. Cardiac magnetic resonance imaging and computed tomography are ideal methods for identifying and following over time patients with calcific degeneration in the heart.

Actual concept of "probiotics":Is it more functional to science or business?

It is our contention that the concept of a probiotic as a living bacterium providing unspecified health benefits is inhibiting the development and establishment of an evidence base for the growing field of pharmacobiotics.We believe this is due in part to the current regulatory framework,lack of a clear definition of a probiotic,the ease with which currently defined probiotics can be positioned in the market place,and the enormous profits earned for minimum investment in research.To avoid this,we believe the following two actions are mandatory:international guidelines by a forum of stakeholders made available to scientists and clinicians,patient organizations,and governments;public research funds made available to the scientific community for performing independent rigorous studies both at the preclinical and clinical levels.

Nonalcoholic fatty liver disease and diabetes

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression.The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux.Strong epidemiological,biochemical,and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance;thus the association between diabetes and NAFLD is widely recognized in the literature.Since NAFLD is the hepatic manifestation of a metabolic disease,it is also associated with a higher cardiovascular risk.Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis,although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients.Treatment of NAFLD patients depends on the disease severity,ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis.Abstinence from alcohol,a Mediterranean diet,and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events,as per all diabetic patients.In addition,weight loss induced by bariatric surgery seems to also be effective in improving liver features,together with the benefits for diabetes control or resolution,dyslipidemia,and hypertension.Finally,liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries.This review offers a comprehensive multidisciplinary approach to NAFLD,highlighting its connection with diabetes.

Negative association between trunk fat, insulin resistance and skeleton in obese women

AIM: To evaluate the potential interference of trunk fat (TF) mass on metabolic and skeletal metabolism. METHODS: In this cross-sectional study, 340 obese women (mean age: 44.8 ± 14 years; body mass index: 36.0 ± 5.9 kg/m 2 ) were included. Patients were evaluated for serum vitamin D, osteocalcin (OSCA), inflammatory markers, lipids, glucose and insulin (homeostasis model assessment of insulin resistance, HOMA-IR) levels, and hormones profile. Moreover, all patients underwent measurements of bone mineral density (BMD;at lumbar and hip site) and body composition (lean mass, total and trunk fat mass) by dual-energy X-ray absorptiometry. RESULTS: Data showed that: (1) high TF mass was inversely correlated with low BMD both at lumbar (P < 0.001) and hip (P < 0.01) sites and with serum vitamin D (P < 0.0005), OSCA (P < 0.0001) and insulin-like growth factor-1 (IGF-1; P < 0.0001) levels; (2) a positive correlation was found between TF and HOMA-IR (P < 0.01), fibrinogen (P < 0.0001) and erythrocyte sedimentation rate (P < 0.0001); (3) vitamin D levels were directly correlated with IGF-1 (P < 0.0005), lumbar (P < 0.006) and hip (P < 0.01) BMD; and (4) inversely with HOMA-IR (P < 0.001) and fibrinogen (P < 0.0005). Multivariate analysis demonstrated that only vitamin D was independent of TF variable. CONCLUSION: In obese women, TF negatively correlates with BMD independently from vitamin D levels. Reduced IGF-1 and increased inflammatory markers might be some important determinants that account for this relationship.

A case of leptospirosis simulating colon cancer with liver metastases

We report a case of a 61-year-old man who presented with fatigue, abdominal pain and hepatomegaly. Computed tomography (CT) of the abdomen showed hepatomegaly and multiple hepatic lesions highly suggestive of metastatic diseases. Due to the endoscopic finding of colon ulcer, colon cancer with liver metastases was suspected. Biochemically a slight increase of transaminases, alkaline phosphatase and gammaglutamyl transpeptidase were present; α-fetoprotein, carcinoembryogenic antigen and carbohydrate 19-9 antigen serum levels were normal. Laboratory and instrumental investigations, including colon and liver biopsies revealed no signs of malignancy. In the light of spontaneous improvement of symptoms and CT findings, his personal history was revaluated revealing direct contact with pigs and their tissues. Diagnosis of leptospiroSis was considered and confirmed by detection of an elevated titer of antibodies to leptospira. After two too, biochemical data, CT and colonoscopy were totally normal.

Surgical treatment for functional mitral regurgitation secondary to dilated cardiomyopathy: Current options and future trends

There is an increasing number of patients with mitral regurgitation secondary to dilated cardiomyopathy. Recent data suggest that mitral regurgitation (MR) can be surgically corrected in heart failure with symptomatic improvements and favourable reverse left ventricular remodeling. However, several questions remain to be answered, regarding the optimal management of functional mitral regurgitation, the correct timing of surgery and the choice of the surgical technique to perform in patients affected by dilated cardiomyopathy. In the setting of ischemic chronic cardiomyopathy, data derived from the recent literature suggest that concomitant severe ischemic MR should be addressed during CABG to improve survival and quality of life. Most surgeons perform concomitant CABG and mitral valve surgery in patients with ischemic chronic cardiomyopathy and moderate to severe MR. In the setting of chronic dilated cardiomyopathy, most clinicians would agree that correction of severe MR in heart failure is warranted, mostly due to a symptomatic benefit and reduction of number of re-hospitalizations. Moreover, reverse ventricular remodeling has been demonstrated with undersized annuloplasty rings and correction of MR: this could lead to improved contractility, reduction in left ventricular end-diastolic and end-systolic volumes, and finally to improved NYHA functional class. Recent large studies suggest that patients undergoing mitral valve repair had improved perioperative survival, shorter length of stay, and improved long-term survival than those undergoing mitral valve replacement because the preservation of the subvalvular apparatus seems to result in superior left ventricular remodelling and in greater improvement in NYHA class. In the near future, data from multi-institutional, randomized prospective trials will help to elucidate many of the questions and concerns regarding repair of severe functional mitral regurgitation. Finally, technology applied to heart surgery is continually evolving and will allow more exciting cellular and novel device therapies for the treatment of functional mitral regurgitation secondary to dilated cardiomyopathy.

Seropositivity for Hepatitis B Virus, Vaccination Status and Response to Vaccine in a Cohort of Dental Students

Background: The development of a vaccine against hepatitis B virus (HBV) has been a major achievement in terms of prevention of HBV infection. To evaluate the immunological status against HBV of dental-profession students, we analysed the long-term immunogenicity and effectiveness of HBV vaccination in Italian dental students with different work seniorities, determining the influence of epidemiological variables on the immune response. Methods: This study, carried out from January 2014 to April 2016, involved 361 under- and post-graduate dental students attending the Second University of Naples. HBV serum markers were determined and multivariate logistic regression analysis was used to identify factors associated with the level of long-term immunogenicity. Results: Of the 361 subjects evaluated, 15 (4.2%) declared no history of vaccination. All vaccinated subjects were HBsAg/anti-HBc negative, with 86 (24.9%) having an anti-HBs titre <10 IU/L. The latter were younger, more likely to be attending undergraduate dental school, and more likely to have been vaccinated in infancy. Conclusion: The findings of this study suggest that assessment of HBV serum markers in workers potentially exposed to hospital infections is useful to identify small numbers of unvaccinated subjects or vaccinated subjects with low antibody titre, all of whom should be referred for a booster series of vaccinations.

Comparison of continuous versus pulsatile dopaminergic therapy in the erderly with Parkinson’s Disease

Objective: Levodopa is the gold-standard of therapy in Parkinson’s disease (PD), but it is associated with motor complications that affect 50% of patients after five years of treatment. Development of delirium and psychosis is the main limitation of dopaminergic treatment in older persons. These adverse effects may result from pulsatile stimulation of the dopamine receptors. Dopamine agonists with transdermal delivery that continuously stimulate the dopamine receptors may reduce these complications. The objective of this study was to evaluate the frequencies of acute delirium and psychosis in elderly patients treated with rotigotine vs. levodopa in a newly diagnosed drugnaive Parkinson’s disease (PD). Methods: Patients admitted to the Geriatric-Rehabilitation Department of the University-Hospital of Parma were screened for the presence of Parkinsonism. All subjects admitted with diagnosis of PD according to the UK Brain Bank Criteria were randomly treated with Rotigotine or levodopa. All subjects were assessed by Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III. Acute delirium was asessed by CAM Diagnostic Algorithm during the first week after admission. After six months, diagnosis of psychosis was performed according to pro posed diagnostic criteria by NINDS and NIMH. Patients with cognitive impairment (MMSE dementia with Lewy bodies (DLB), were excluded. Results: 60 consecutive newly diagnosed drugnaive PD patients were evaluated. No statistical significant difference between the two groups were observed in term of age, gender, MMSE score, severity of disease expressed by H&Y staging. 30 patients were treated with rotigotine (6 mg/daily) and 30 patients were treated with L-Dopa (250 mg/daily). All participants completed the study. UPDRS Part III was statistical significant lower in both groups after treatment from 26.4 to 18.3 (rotigotine group) and from 26.3 to 17.3 (levodopa group), but comparable within groups (p = 0.83). After 6-month follow-up, acute delirium and/ or psychosis were observed in two cases (6.6%) of patients treated with rotigotine and in three cases (10%) of those treated with levodopa (p = 0.54). Conclusions: Transdermal rotigotine seems comparable to levodopa in regard to motor skill efficacy and neuropsychiatric safety, because provides a more continuous delivery of drug. Dopamine agonists may represent a valid therapeutic option in newly diagnosed older PD patients.

Active surveillance of adverse drug reactions in children in five Italian paediatric wards

Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.

Bisphosphonates and adipogenesis: Evidence for alendronate inhibition of adipocyte differentiation in 3T3-L1 preadipocytes through a vitamin D receptor mediated effect

Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.

Is Autonomic Nervous System Involved in the Epileptogenesis in Preterm Neonates?

Autonomic nervous system dysfunction has been described with focal and generalized epileptic seizures;occurring during their ictal,interictal,or postictal states.International League Against Epilepsy Seizure Classification Manual defines autonomic seizures as a distinct alteration of autonomic nervous system function involving cardiovascular,pupillary,gastrointestinal,sudomotor,vasomotor,and thermoregulatory functions.Autonomic seizures represent a great challenge for neonatologists and neurophysiologists;and distinguishing between ictal and non-ictal autonomic changes in neonates is rarely straightforward,especially in the premature ones.To avoid overdiagnosis and overtreatment,International League Against Epilepsy and the American Clinical Neurophysiology Society currently require electrographic correlation for any seizure diagnosis,including preterm neonates.There is very little scientific evidence about the pathophysiology of autonomic seizures.The data reporting on their incidence,clinical features,and diagnostic pathway is also insufficient.In this paper,we hypothesize that in the developing brain of preterm neonates,seizures involving deeper autonomic networks and subcortical structures might not propagate sufficiently to the cortex,and therefore the association of the seizures with specific ictal electrographic changes on surface electroencephalogram might be lacking.We propose considering autonomic seizures in the differential diagnosis of unexplained autonomic changes in neonates,especially preterm neonates,even in the absence of clear initial electrographic correlation.Unexplained autonomic changes could therefore be thought of as a“seizure alarm”in this population.

Management of patients with melanoma and non-melanoma skin cancers in the coronavirus disease 2019 era

The recent coronavirus disease 2019(COVID-19)pandemic has completely disrupted hospital and outpatient activities.[1,2]It has been reorganized to allow a lower inflow of patients,to reduce non-urgent out-patient visits and to concentrate public health forces in the fight against the COVID-19 outbreak.In this reorganization,dermatology departments have also adapted their activities suspending routine patient visits and providing only urgent surgical removal,urgent visits,consultations,and oncological examinations.

迟发性性腺功能减退症与骨化二醇的关系

男性迟发性性腺功能减退症是指具有血清睾酮（T）水平降低和典型临床症状的综合征。而血清睾酮浓度是否总能真实反应Leydig细胞的功能目前仍不确定。轻度睾丸改变只有通过检测额外的生化标记物如黄体生成素（LH）和25．羟维生素D才能确诊。这些标记物可以帮助诊断称之为“亚临床”型的性腺功能减退（血清睾酮正常，LH升高）。性腺功能减退患者通常由于睾丸中CYP2Rt羟化酶受损而具有较低水平的25．羟维生素D。然而，目前仍无证据阐释维生素D3亦或骨化二醇是治疗此类病人的最佳选择。因此我们分析了26位具有典型性腺功能减退患者（总T[TT]〈12nmol 1^-1，LH≥8IU 1^-1）及46位亚临床型性腺功能减退患者（TT≥12nmol 1^-1，LH≥8IU 1^-1）以及低25-羟维生素D患者（〈50nmol 1^-1）。其中20名患者接受每周5000IU的维生素D3治疗，46名患者接受每周4000IU的骨化二醇治疗。治疗3个月后，患者25-羟维生素D及甲状旁腺激素升高。在两组患者中（原发型16人，亚临床型30人）补充骨化二醇可以显著提高25-羟维生素D水平并显著降低甲状旁腺激素水平，而补充维生素D3的患者，其25-羟维生素D和甲状旁腺激素水平并无明显变化。本研究首次阐述服用骨化二醇而非维生素D3，可以提高男性迟发性性腺功能减退患者25-羟维生素D水平。

MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution

Organisms and cells,in response to environmental influences or during development,undergo considerable changes in DNA methylation on a genome-wide scale,which are linked to a variety of biological processes.Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly.In this study,we develop a novel approach,named MBRidge,to detect the methylation levels of repertoire CpGs,by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis.A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation(R>0.90)with much less cost(∼10%)in comparison with MethylC-seq.We further applied MBRidge to profiling DNA methylome in T29H,an oncogenic counterpart of T29’s.By comparing methylomes of T29H and T29,we identified 131790 differential methylation regions(DMRs),which are mainly enriched in carcinogenesis-related pathways.These are substantially different from7567 DMRs that were obtained by RRBS and related with cell development or differentiation.The integrated analysis ofDMRsin the promoterand expression of DMR-corresponding genes revealed thatDNAmethylation enforced reverse regulation of gene expression,depending on the distance fromthe proximalDMRto transcription starting sites in both mRNA and lncRNA.Taken together,our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.