Impact of gastroesophageal reflux control through tailored proton pump inhibition therapy or fundoplication in patients with Barrett's esophagus

AIM To determine the impact of upwards titration of proton pump inhibition(PPI) on acid reflux, symptom scores and histology, compared to clinically successful fundoplication.METHODS Two cohorts of long-segment Barrett's esophagus(BE) patients were studied. In group 1(n = 24), increasing doses of PPI were administered in 8-wk intervals until acid reflux normalization. At each assessment, ambulatory 24 h p H recording, endoscopy with biopsies and symptom scoring(by a gastroesophageal reflux disease health related quality of life questionnaire, GERD/HRLQ) were performed. Group 2(n = 30) consisted of patients with a previous fundoplication. RESULTS In group 1, acid reflux normalized in 23 of 24 patients, resulting in improved GERD/HRQL scores(P = 0.001), which were most pronounced after the starting dose of PPI(P < 0.001). PPI treatment reached the same level of GERD/HRQL scores as after a clinically successful fundoplication(P = 0.5). Normalization of acid reflux in both groups was associated with reduction in papillary length, basal cell layer thickness, intercellular space dilatation, and acute and chronic inflammation of squamous epithelium. CONCLUSION This study shows that acid reflux and symptom scores co-vary throughout PPI increments in long-segment BE patients, especially after the first dose of PPI, reaching the same level as after a successful fundoplication. Minor changes were found among GERD markers at the morphological level.

Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement

Introduction: The rearrangement of the anaplastic lymphoma kinase(ALK) gene accounts for approximately 1%–6% of lung adenocarcinoma cases and deines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinico?pathologic characteristics of non?small cell lung cancer(NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.Methods: A total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization(FISH) assay.Results: Among the 487 patients, 44(9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non?smokers and of a young age(≤58 years old), the frequency of ALK rearrangement was 20.3%(25/123). Short overall survival(OS) was associated with non?adenocarcinoma tumor type(P = 0.006), poorly diferentiated tumors(P al growth factor rece= 0.001), advanced?stage tumors(P < 0.001), smoking history(P ptor(EGFR)(P = 0.008), and wild?type epidermrter time to cancer p= 0.008). Moreover, patients with poorly diferentiated and advanced?stage tumors had a shorogression compared with those with well diferentiated(P = 0.023) and early?stage tumors(P = 0.001), respectively.Conclusions: ALK?rearranged NSCLC tends to occur in younger individuals who are either non?smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might beneit from ALK inhibitor therapy.

Extent of lymphadenectomy has no impact on postoperative complications after gastric cancer surgery in Sweden

Objective： Curative gastric cancer surgery entails removal of the primary tumor with adequate margins including regional lymph nodes. European randomized controlled trials with recruitment in the 1990＇s reported increased morbidity and mortality for D2 compared to D 1. Here, we examined the extent of lymphadenectomy during gastric cancer surgery and the associated risk for postoperative complications and mortality using the strengths of a population-based study. Methods： A prospective nationwide study conducted within the National Register of Esophageal and Gastric Cancer. All patients in Sweden from 2006 to 2013 who underwent gastric cancer resections with curative intent were included. Patients were categorized into DO, D I, or D I ＋/D2, and analyzed regarding postoperative morbidity and mortality using multivariable logistic regression. Results： In total, 349 （31.7%） patients had a DO, 494 （44.9%） DI, and 258 （23.4%） DI＋/D2 lymphadenectomy. The 30-d postoperative complication rates were 25.5%, 25.1% and 32.2 % （DO, D I and D1 ＋/D2, respectively）, and 90-d mortality rates were 8.3%, 4.3 % and 5.8%. After adjustment for confounders, in mukivariable analysis, there were no significant differences in risk for postoperative complications between the lymphadenectomy groups. For 90-d mortality, there was a lower risk for D1 vs. DO. Conclusions： The majority of gastric cancer resections in Sweden have included only a limited lymphadenectomy （DO and DI）. More extensive lymphadenectomy （DI＋/D2） seemed to have no impact on postoperative morbidity or mortality.

Knowledge of COVID-19 and its prevention among rural residents in Fuqing,China

Objectives:Rural areas are the weakest place for epidemic prevention and control,yet few studies have specifically conducted surveys in rural areas.The purpose of this study is to assess rural residents’knowledge of the COVID-19 and its prevention in China.Methods:A cross-sectional survey study containing 1,426 samples was conducted in Fuqing,China to assess rural residents’knowledge of the COVID-19 and its prevention.Logistic regression was used to identify potential differences in participants’knowledge of COVID-19 and its prevention and control in different population subgroups.Results:The mean and median of residents’knowledge of COVID-19 was 5.53 and 6 points,respectively.The mean and median of residents’knowledge related to self-protection against COVID-19 was 10.34 and 11 points,respectively.Older adults(AOR45e59=2.26,95%CI 1.20 to 4.27;AOR60-69=3.13,95%CI 1.63 to 5.98;AOR70=4.68,95%CI 2.35 to 9.33)were more deficient in knowledge of COVID-19.Those who were better educated and with a higher average annual household income were less likely to be deficient in the knowledge of COVID-19 and knowledge of self-protection against COVID-19.Moreover,those who were single,divorced,or widowed(AOR=1.67,95%CI 1.13 to 2.46)were more deficient in the knowledge of self-protection against COVID-19.Conclusions:Our study suggests that when facing a pandemic like COVID-19,the key is to inform the public to understand simple and effective self-protection measures.Therefore,we call on the govern-ments to give priority to publicity and education on self-prevention measures for the targeted pop-ulations and regions.This is most evident among the vulnerable groups like those who were unmarried,elderly,and those with low education or low income.Similar suggestions may be of use in other countries as well.

Clinical relevance of cancer genome sequencing

The arrival of both high-throughput and bench-top next-generation sequencing technologies and sequence enrichment methods has revolutionized our approach to dissecting the genetic basis of cancer. These technologies have been almost invariably employed in wholegenome sequencing (WGS) and whole-exome sequencing (WES) studies. Both WGS and WES approaches have been widely applied to interrogate the somatic mutational landscape of sporadic cancers and identify novel germline mutations underlying familial cancer syndromes. The clinical implications of cancer genome sequencing have become increasingly clear, for example in diagnostics. In this editorial, we present these advances in the context of research discovery and discuss both the clinical relevance of cancer genome sequencing and the challenges associated with the adoption of these genomic technologies in a clinical setting.

中国的恶性肿瘤:从第1次全国死亡调查到最新的国家癌症登记,中国癌症地图变迁带来的启示

背景与目的在过去的40年里,中国共开展了3次全国范围的死因调查,并逐步建立了癌症登记制度。为了更好地了解中国的癌症疾病负担及其预防策略,本研究分析了40年来的恶性肿瘤的死亡情况,并梳理了已或待实施的恶性肿瘤的预防策略。方法基于1973–1975年、1990–1992年、2004–2005年3次全国死因调查的数据及我国国家癌症登记中心公布的最新癌症登记数据,本研究描述了中国主要恶性肿瘤的死亡率及其时空变化。根据Segi’s世界标准人口计算年龄标准化死亡率后,比较各死亡率的数据。通过在地图上标记主要恶性肿瘤的高发地区,探讨其地理分布特征及变化。结果1973–2016年,我国胃癌、食管癌、宫颈癌的死亡率明显下降,而肺癌、结直肠癌、女性乳腺癌的死亡率逐渐上升。自2004年以来,肝癌的死亡率略微下降。在过去的20年里,肺癌和肝癌已经成为我国恶性肿瘤的两大主要死因。3次全国死因调查显示,城市和农村地区的主要恶性肿瘤的死因模式相似。但是,城市地区的食管癌和胃癌死亡率均低于农村地区。1973–1975年,农村地区五大主要恶性肿瘤死因的死亡率与同时期小城市地区相似。此外,2016年农村地区的五大主要恶性肿瘤的死因的死亡率也与2004–2005年城市地区接近。胃癌、食管癌和肝癌呈现出区域聚集性高发。自1990年至2016年,尽管这些恶性肿瘤的大多数高发地区的死亡率有所下降,但仍高于同期全国平均水平。结论进一步强化我国的初级公共卫生体系,特别是在农村地区,可能是减轻我国恶性肿瘤负担的关键一步。

植根区域生长法(SRG)中的边界像素及其改进算法(英文)

根植区域生长法(Seeded Region Growing)是处理图象分割的一种快捷的半自动算法([1],R.Adams and L.Bischof,1994),也是目前处理图象问题的一种公认的有效方法和技术.边界像素对该算法的行为及效果有着微妙的但却是重要的.在应用中我们发现,当分割块处于狭窄连通状态时,这一算法常常是失败的,而失败的结果通常会导致原始图象的细节失真或者过分地依赖种子的选择.针对这一问题,我们对R.Adams和L.Bischof的植根区域生长法进行了改进,给出了一个有效算法,解决了原来算法对狭窄连通分割块失败的问题.

药物流行病学研究中处理偏倚的方法

药物流行病学是在应对处理药源性疾病、药物不良反应过程中发展起来的一门医药学领域的综合应用性学科,是流行病学的分支之一。正确评价药物在人群中的利用及其效应主要取决于合理的研究设计和得当的实施和分析方法来控制系统误差。本文基于《中国药物流行病学研究方法学指南》,检索相关文献,并结合实例,对药物流行病学研究中处理偏倚的方法进行解读,系统理解处理偏倚的方法。当前国内药物流行病学研究对偏倚处理的方法仍需加强,需重点关注选择偏倚、错分偏倚、混杂偏倚、时间依赖性偏倚、系统评价,根据产生原理及过程,在试验设计阶段使用随机化、盲法、限制、匹配等方法消除或减少偏倚,系统评价时采用漏斗图、秩相关分析法、回归分析法、剪补法等评估发表偏倚,提高药物流行病学在医学中的价值,促进全民健康发展。

Diabetes and cancer: Epidemiological and biological links

The incidence of diabetes and cancer has increased significantly in recent years.Furthermore,there are many common risk factors for both diabetes and cancer,such as obesity,sedentary lifestyle,smoking,and ageing.A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death.The incidence and mortality of various types of cancer,such as pancreas,liver,colorectal,breast,endometrial,and bladder cancers,have a modest growth in diabetics.However,diabetes may work as a protective factor for prostate cancer.Although the underlying biological mechanisms have not been totally understood,studies have validated that insulin/insulin-like growth factor(IGF)axis(including insulin resistance,hyperinsulinemia,and IGF),hyperglycemia,inflammatory cytokines,and sex hormones provide good circumstances for cancer cell proliferation and metastasis.Insulin/IGF axis activates several metabolic and mitogenic signaling pathways;hyperglycemia provides energy for cancer cell growth;inflammatory cytokines influence cancer cell apoptosis.Thus,these three factors affect all types of cancer,while sex hormones only play important roles in breast cancer,endometrial cancer,and prostate cancer.This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Diabetic kidney disease(DKD)is one of the major chronic complications of diabetes mellitus(DM),as well as a main cause of end-stage renal disease.Over the last few years,substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD.Metabolites of gut microbiota like lipopolysaccharide,short-chain fatty acids,and trimethylamine N-oxide are key mediators of microbial–host crosstalk.However,the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown.Besides,strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently,representing a new potential remedial target for DKD.In this minireview,we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

成年人慢性肾脏病患者感染新型冠状病毒治疗药物选择——基于循证医学证据

慢性肾脏病(CKD)以尿检异常或肾功能进行性下降为特征。CKD患者因肾功能受损、长期使用影响免疫系统的药物或合并基础疾病较多,较正常人群更容易感染新型冠状病毒(COVID-19),且感染后重症转化率及死亡率更高。对于CKD合并COVID-19感染的治疗,合理用药尤为重要。为此,本文通过整合目前治疗COVID-19相关药物的最新研究证据,包括抗病毒药物、抗炎药物、抗血栓药物、康复者恢复期血浆与中和单克隆抗体,以及呼吸系统疾病常用对症治疗药物(如解热、止咳化痰及抗过敏药物等),突出在不同肾功能水平的调整用药方案,总结在CKD患者中使用相关药物的特殊考虑要点,以期供临床专业人员参考,辅助临床决策和合理用药,保障临床疗效与安全性。

Adherence to medication: A nation-wide study from the Children's Cancer Hospital, Egypt

AIM: To investigate adherence to medical regimen and predictors for non-adherence among children with cancer in Egypt. METHODS: We administered two study specific questionnaires to 304 parents of children diagnosed with cancer at the Children's Cancer Hospital in Cairo, Egypt, one before the first chemotherapy treatment and the other before the third. The questionnaires were translated to colloquial Egyptian Arabic, and due, to the high illiteracy level in Egypt an interviewer read thequestions in Arabic to each parent and registered the answers. Both questionnaires consisted of almost 90 questions each. In addition, a Case Report Form was filled in from the child's medical journal. The study period consisted of 7 mo(February until September 2008) and we had a participation rate of 97%. Descriptive statistics are presented and Fisher's exact test was used to check for possible differences between the adherent and non-adherent groups. A P-value below 0.05 was considered significant. Software used was SAS version 9.3 for Windows(SAS Institute Inc., Cary, NC, United States).RESULTS: Two hundred and eighty-one(90%) parents answered the second questionnaire, regarding their child's adherence behaviour. Approximately two thirds of the children admitted to their third chemotherapy treatment had received medical recommendations upon discharge from the first or second chemotherapy treatment(181/281, 64%). Sixty-eight percent(123/181) of the parents who were given medical recommendations reported that their child did not follow the recommendations. Two main predictors were found for non-adherence: child resistance(111/123, 90%) and inadequate information(100/123, 81%). In the adherent group, 20% of the parents(n = 12/58) reported trust in their child's doctor while 14 percent 8/58 reported trust in the other health-care professionals. Corresponding numbers for the non-adherent group are 8/123(7%) for both their child's doctor and other health-care professionals. Almost all of the parents expressed a lack of optimism towards the treatment(116/121, 96%), yet they reported an intention to continue with the treatment for two main reasons, for the sake of their child's life(70%)(P = 0.005) and worry that their child would die if they discontinued the treatment(81%)(P < 0.0001).CONCLUSION: Non-adherence to medical regimen is common among children diagnosed with cancer inEgypt, the main reasons being child resistance and inadequate information.

Letters to the Editor

The Editor welcomes submissions for possible publication in the Letters to the Editor section.Letters commenting on an article published in the Journal or other interesting pieces will be considered if they are received within 6 weeks of the time the article was published.Authors of the article being commented on will be given an opportunity to offer a timely response to the letter Authors of letters will be notified that the letter has been received. Unpublished letters cannot be returned.

远端食管和胃-食管连接处癌前病变和其他化生的发病

Objective. The epidemiology of Barrett’ s oesophagus (BO) is characterized by divergent results. The aim of this study was to estimate the prevalence of BO and intestinal metaplasia (IM) at the gastro- oesophageal junction (GOJ) in a population- based series of patients referred for first- time gastroscopy. Material and methods. Consecutive patients who underwent endoscopy for the first time at endoscopy units exclusively serving defined catchment areas were invited to take part in the study. Biopsies were taken immediately below the GOJ and from the distal oesophagus, and clinical data were recorded. Results. A total of 769 patients (mean age 53 years, 43% M) were examined. Overall IM prevalence was 14% . BO was noted in 4% . Overall, the prevalence of IM increased by 8% (95% CI 6- 10% ) per year of age. BO patients were predominately women (69% ). Presence of cardia- type mucosa in the cardia increased with age from 25% among the youngest to 59% among the oldest patients. Pancreatic acinar metaplasia (PAM) was found in 18% . Conclusions. While BO is not common among Swedish gastroscopy patients, IM and PAM are found in every 7th and 6th patient, respectively. Age- dependent increments in prevalence suggest that not only BO and IM, but also cardia- type mucosa are acquired and/or progressive lesions.

Investigation of mental health and its influence on Chinese cancer patients using a multidisciplinary screening flow： an epidemiological survey in the west of China

Background Despite psycho-oncological concerns and studies having thrived these past decades, sparse reports illustrate to what extent Chinese cancer patients are involved and influenced by comorbid mental health problems. To investigate the mental health condition of cancer patient, as well as its possible impacts on prognosis, the first large-scale survey was performed in the west of China. Methods For standardizing and facilitating the assessment of mental illness in inpatients with cancer, a multidisciplinary rating flow was designed and established. On the basis of this system, between May 1st and 31st 2009, 2279 cancer inpatients from nine medical centers received preliminarily screening executed by oncologists using screening scales Mental Health Screening Questionnaire （MHSQ）, Zung self-rating depression scales （SDS）, Zung self-rating anxiety scale （SAS）, and posttraumatic stress disorder checklist-civilian version （PCL-C）. Further analyses of the ones screened positively were conducted by psychiatrists applying corresponding symptom-rating scales （HAMNHAMD/BPRS）. We summarized the overall proportion of patients with impaired mental health based on the data acquired from preliminary screening, and then calculated occurrence rates of each clinical syndrome of mental disorder according to symptom conclusions. The impact of comorbid mental illness was evaluated through the follow-up scheduled 1 year later, by comparing the survival rate, progression of disease, and quality of life （QoL） between subgroup patients with or without clinical syndrome of mental disorder. Results In preliminary screenings, 26.1% （595/2279） yielded positive results. Further symptom conclusions confirmed 15.8% （359/2279） with clinical syndrome of mental disorder. Regarding specific type of syndrome, the occurrence rates of depression, anxiety, psychotic symptoms, and stress-related disorders were 13.3%, 10.2%, 2.8%, and 1.4%, respectively. Follow-up assessments were successfully performed in 1918 subjects （84.2%）. Further analyses indicated that although insignificant influence was observed in terms of 1-year survival rate and disease progression, cancer patients with a clinical syndrome of mental disorder obtained significantly lower levels （P 〈0.05） in five domains of QoL （scored by QLQ-C30）. Conclusion In China, at least 26% of cancer patients experienced impaired mental health, of which 60% already had a detectable clinical syndrome of mental disorder, which could significantly undermine their QoL.

Determinants of China’s development assistance for health at the sub-national level of African countries(2006-2015)

Background:Despite the increasing interest in China’s development assistance for health(DAH)in African countries,little is known regarding the distribution and determinants of China’s DAH project allocation among the principle subdivisions(provinces&states)within African countries.Methods:We mapped the distribution of China’s DAH projects in 670 principle subdivisions of 50 African countries during 2006-2015 using web-based information.The political,demographic,health and socioeconomic indicators of DAH allocation were analyzed using conditional logistic regression models.The national capital city and political leader’s birth place were selected as the main political indicators,and health indicators were selected according to different fields of the DAH projects.Results:China’s DAH projects(mainly China medical teams[CMTs],hospitals and anti-malaria centers)were mostly allocated to the western and eastern coasts of Africa,although CMTs were also dispatched to northern Africa.National capital cities were significantly associated with the allocation of China’s DAH projects(P<0.001).Antimalaria centers were more likely to be allocated to principle subdivisions with larger populations(OR=1.35),and CMTs were allocated to subdivisions with high population densities(OR=79.01).No health-related indicators were identified to affect project allocation except for the facility delivery rate and under-five mortality rate,which were associated with hospital allocation.We also found an association between CMT allocation and the use of artemisinin-based combination therapy in children.Conclusions:Allocation of China’s DAH projects is strongly affected by political and demographic factors.Implementation of China’s new DAH projects should target health and socio-economic indicators and impact metrics in scaling up tailored and cost-effective programs in Africa.

Psychological and physiological impacts of a fast-track diagnostic workup for men with suspected prostate cancer:Preliminary report from a randomized clinical trial

Dear Editor,The increasing number of men who undergo workup for suspected prostate cancer are subject to severe emotional stress[1].Stress levels seem to be elevated as soon as a suspicion of cancer is raised and the waiting time before a final diagnosis may be equally stressful as the post-diagnostic period[1,2].We recently demonstrated a marked increase in risk for different psychiatric disorders during the six months before prostate cancer diagnosis,highlighting the potential impact of emotional stress experienced while waiting for the diagnosis[3].

Inflammation as a Mediator of Microbiome Dysbiosis-Associated DNA Methylation Changes in Gastric Premalignant Lesions

Evidence for the influence of chronic inflammation induced by microbial dysbiosis on aberrant DNA methylation supports a plausible connexion between disordered microbiota and precancerous lesions of gastric cancer(PLGC).Here,a comprehensive study including multi-omics data was performed to estimate the relationships amongst the gastric microbiome,inflammatory proteins and DNA methylation alterations and their roles in PLGC development.The results demonstrated that gastric dysbacteriosis increased the risk of PLGC and DNA methylation alterations in related tumour suppressor genes.Seven inflammatory biomarkers were identified for antrum and corpus tissues,respectively,amongst which the expression levels of several biomarkers were significantly correlated with the microbial dysbiosis index(MDI)and methylation status of specific tumour suppressor genes.Notably,mediation analysis revealed that microbial dysbiosis partially contributed to DNA methylation changes in the stomach via the inflammatory cytokines C-C motif chemokine 20(CCL20)and tumour necrosis factor receptor superfamily member 9(TNFRSF9).Overall,these results may provide new insights into the mechanisms that might link the gastric microbiome to PLGC.

Hidden Genetic Regulation of Human Complex Traits via Brain Isoforms

Alternative splicing exists in most multi-exonic genes,and exploring these complex alternative splicing events and their resultant isoform expressions is essential.However,it has become conventional that RNA sequencing results have often been summarized into gene-level expression counts mainly due to the multiple ambiguous mapping of reads at highly similar regions.Transcript-level quantification and interpretation are often overlooked,and biological interpretations are often deduced based on combined transcript information at the gene level.Here,for the most variable tissue of alternative splicing,the brain,we estimate isoform expressions in 1,191 samples collected by the Genotype-Tissue Expression(GTEx)Consortium using a powerful method that we previously developed.We perform genome-wide association scans on the isoform ratios per gene and identify isoform-ratio quantitative trait loci(irQTL),which could not be detected by studying gene-level expressions alone.By analyzing the genetic architecture of the irQTL,we show that isoform ratios regulate edu-cational attainment via multiple tissues including the frontal cortex(BA9),cortex,cervical spinal cord,and hippocampus.These tissues are also associated with different neuro-related traits,including Alzheimer’s or dementia,mood swings,sleep duration,alcohol intake,intelligence,anxiety or depression,etc.Mendelian randomization(MR)analysis revealed 1,139 pairs of isoforms and neuro-related traits with plausible causal relationships,showing much stronger causal effects than on general diseases measured in the UK Biobank(UKB).Our results highlight essential transcript-level biomarkers in the human brain for neuro-related complex traits and diseases,which could be missed by merely investigating overall gene expressions.

中国非儿童癌症患者脓毒血症流行情况及地域分布:一项全国横断面研究

Cancer poses a major public health burden worldwide,with approximately 18,094,716 newly diagnosed cases and 9,894,402 cancer-related deaths in 2020[1].Infections such as sepsis are among the leading causes of death in this population after cancer itself[2].