Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis

BACKGROUND： There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis（PC）, which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor（EGFR） inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.METHODS： After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.RESULTS： The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and β-glucuronidase activity.CONCLUSION： Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.

Selective deletion of the soluble Colony-Stimulating Factor 1 isoform in vivo prevents estrogen-deficiency bone loss in mice

Neutralizing CSF1 in vivo completely prevents ovariectomy （OVX）-induced bone loss in mice. There are two isoforms of CSF1, soluble （sCSF1）, and membrane-bound （mCSF1）, but their individual biological functions are unclear. It had been previously reported that mCSF1 knockout （K/O） and wild type （Wt） female mice experience the same degree of bone loss following OVX. In Wt mice the expression of sCSF1 was elevated fourfold in skeletal tissue following OVX while expression of mCSF1 was unchanged. To examine the role of sCSF1 in OVX-induced bone loss, mice were engineered in which sCSF1 was not expressed but expression of mCSF1 was unaffected （sCSF1 K/O）. Isoform-specific reverse transcription PCR confirmed the absence of transcripts for sCSF1 in bone tissue isolated from these animals and no circulating CSF1 was detected by ELISA. Surprisingly, there were no significant differences in bone mineral density （BMD） between sCSF1 K/O mice and Wt controls as assessed by dual-energy X-ray absorptiometry and micro-CT. However, one month after OVX, femoral, spinal and total BMD had declined by 11.2%, 8.9%, and 8.7% respectively in OVX-Wt animals as compared to Sham-OVX. In contrast OVX sCSF1 K/O mice showed changes of ＋0.1%, - 2.4%, and ＋2.3% at the same 3 sites compared to Sham-OVX sCSF1 K/O mice. These data indicate important non-redundant functions for the two isoforms of CSF1 and suggest that sCSF1, but not mCSF1, plays a key role in estrogen-deficiency bone loss.

Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

The aging burden of hospitalization for heart failure in Chinese populations:evidence from the Macao Heart Failure Study

Objective To assess the aging burden of hospitalization for heart failure in Chinese populations in Macao.Methods The Macao Heart Failure Study consists of patients hospitalized with a diagnosis of acute heart failure(AHF)at Centro Hospitalar Conde de São Januário(the only public hospital that provides medical care for the approximately 600,000 residents of Macao)from January 2014 to December 2016.First,we investigated the relationship between socioeconomic development and epidemiological characteristics of HF in Macao.Then we assessed the patients’clinical features and outcomes according to the age groups.Results A total of 967 patients were included in the final analysis.The median age at admission was 82 years old.The advanced age at the admission of HF in Macao was significantly associated with a high-income level and the aging population structure.Marked heterogeneity existed in the epidemiological characteristics,clinical features,utilization of evidence-based therapies,short-and long-term outcomes,and prognostic utility of clinical variables among the different age groups.Conclusion Rapid economic development and significantly aging populations have produced a profound impact on the epidemiological characteristics of HF in Chinese populations.Acute decompensated heart failure(ADHF)is predominantly a disease of the elderly in Macao,and a significant heterogeneity exists in the clinical features,managements,and outcomes among different age groups.Age-based risk stratification models and multidisciplinary HF teams are urgently needed to improve the management and outcomes of hospitalized heart failure(HHF)patients.

Cerebral ischemia during surgery:an overview

Cerebral ischemia is the pathophysiological condition in which the oxygenated cerebral blood flow is less than what is needed to meet cerebral metabolic demand.It is one of the most debilitating complications in the perioperative period and has serious clinical sequelae.The monitoring and prevention of intraoperative cerebral ischemia are crucial because an anesthetized patient in the operating room cannot be neurologically assessed.In this paper,we provide an overview of the definition,etiology,risk factors,and prevention of cerebral ischemia during surgery.

Software defect prevention based on human error theories

Software defect prevention is an important way to reduce the defect introduction rate.As the primary cause of software defects,human error can be the key to understanding and preventing software defects.This paper proposes a defect prevention approach based on human error mechanisms：DPe HE.The approach includes both knowledge and regulation training in human error prevention.Knowledge training provides programmers with explicit knowledge on why programmers commit errors,what kinds of errors tend to be committed under different circumstances,and how these errors can be prevented.Regulation training further helps programmers to promote the awareness and ability to prevent human errors through practice.The practice is facilitated by a problem solving checklist and a root cause identification checklist.This paper provides a systematic framework that integrates knowledge across disciplines,e.g.,cognitive science,software psychology and software engineering to defend against human errors in software development.Furthermore,we applied this approach in an international company at CMM Level 5 and a software development institution at CMM Level 1 in the Chinese Aviation Industry.The application cases show that the approach is feasible and effective in promoting developers＇ ability to prevent software defects,independent of process maturity levels.