孟德尔随机化分析在结直肠癌血液标志物遗传背景研究中的应用

结直肠癌(colorectal cancer,CRC)是一种发生在结肠和直肠的消化道癌症,是全球第三常见癌症,也是癌症相关死亡的第二大原因。CRC的早期发现对于预防转移、降低死亡率、改善预后和提高患者生活质量至关重要。遗传因素在CRC的发生中扮演重要角色,可解释高达35%的疾病风险。全基因组关联研究已发现多个与CRC风险相关的遗传位点,但缺乏直接因果关系的证据。虽然传统的血液标志物如癌胚抗原(carcinoem-bryonic antigen,CEA)和糖类抗原19-9(CA19-9)已被广泛用于CRC诊断和监测,但在早期诊断应用中的灵敏度和准确性有限,仍需要开发新的能够反映遗传背景的生物标志物或其组合,以促进早期诊断和提高诊断准确性。同时,理解这些生物标志物的遗传机制对于揭示CRC的发病机制至关重要,并有助于开发更加精准的个体化治疗策略。孟德尔随机化(Mendelian randomization,MR)分析作为一种新兴的流行病学工具,通过减少观察性研究中存在的偏差问题,能够更精确地评估遗传变异与疾病间的因果关系。目前,MR分析已被用于评估多种血液标志物对CRC风险的因果影响,可更准确地表明血液标志物与CRC发病机制之间的潜在因果关系。本文综述了MR分析在CRC血液标志物研究中的应用,旨在为CRC的早期诊断和个体化治疗提供理论基础。

Estimating Incubation Period and Predicting Risk of Developing Hepatocellular Carcinoma in Patients with HCV Infection from the Clinic of a County-Level City in China

Background: To estimate incubation period in patients infected with hepatitis C virus (HCV) and to predict patients’ risk of developing hepatocellular carcinoma (HCC) for indicating health policymaking. Methods: An outbreak of HCV infection from a clinic was occurred due to the injection treatment of varicose veins called minimally invasive thrombolysis and meridian activating therapy (MITMT) in a county-level city of China. Conventional method and bootstrapping approach were used to estimate HCV incubation period. Risk assessment model generated from the previous study was applied to predict the risk of developing HCC in the coming 5-, 10-, and 15-year for HCV infected patients from the above outbreak. Results: A total of 120 subjects were underwent MITMT between October 22, 2012 and January 28, 2013;of those, 99 subjects were diagnosed with HCV infection. Mean age of the subjects was 54.42 years old, and females were accounted for 51.5% in contracted subjects. Mean incubation period of hepatitis C (HC) was 45.76 days using first MITMT as infected date and 30.68 days using bootstrapping approach, their standard deviations were 23.01 and 15.05 days, respectively. A total of 1.3, 4.7, and 10.6 persons will be developed into HCC in the coming 5, 10, and 15 years in infected subjects based on a risk prediction model. Conclusion: Some patients with HCV infection from a nosocomial clinic in a county-level city will be suffered from more severe HCC in the coming decade;effective measures and controls were urgently needed to manage these patients with high risk of developing into end-stage liver disease.

Comparison of combined laparoscopic ureterolithotomy and flexible ureteroscopy with percutaneous nephrolithotomy for removing large impacted upper ureteral stones with concurrent renal stones

Objectives:The present study compared the safety and efficacy of combined laparoscopic ureterolithotomy(LU)and flexible ureteroscopy with percutaneous nephrolithotomy(PCNL)for removing large impacted upper ureteral stones with concurrent renal stones.Methods:This study included 52 patients who underwent combined LU and retrograde flexible ureteroscopy for removing renal stones(group A)or PCNL(group B)for removing large upper impacted ureteral stones and concurrent renal stones at our department from January 2014 to December 2016.Patient demographics,stone characteristics,and procedure-related parameters including stone-free rate,operation time,hospital stay after surgery,mean decrease in hemoglobin levels,visual analog scale(VAS)score,auxiliary procedure rate,and complication rate were compared between groups A and B.Results:Results of this study showed that both procedures were effective for removing large impacted upper ureteral stones with concurrent renal stones.The stone-free rate after a single procedure was 95.7%in group A and 89.7%in group B(p?0.62).The operation time was longer in group A than in group B(112.2±23.3 min versus 96.2±16.4 min,p?0.006).However,no significant difference was observed between the two groups with respect to the length of hospital stay after the surgery(5 days versus 6 days,p?0.06).The decrease in hemoglobin levels was significantly higher in group B than in group A(0.64±0.36 g/dL versus1.44±0.65 g/dL,p<0.0001).The mean VAS scores obtained at 24 hours(2.91±1.08 versus 5.10±1.01,p<0.0001)and 48 hours after the surgery(1.09±0.73 versus 2.28±0.96,p<0.0001)were significantly higher for group B than for group A.Moreover,the auxiliary procedure rate was higher in group B than in group A(6.9%versus 0%).Conclusion:These results indicate that both combined LU and flexible ureteroscopy and PCNL are suitable for removing large impacted upper ureteral stones with concurrent renal stones and are associated with a high rate of patients being stone free afterwards.Despite the longer operation time,the combined laparoscopic and endourological procedure may be associated with less postoperative pain and fewer major complications.However,the choice of treatment depends on the preferences of surgeons and patients.

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

Correction:The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling

Correction:Cell Regen 12,30(2023).https://doi.org/10.1186/s13619-023-00174-7 Following publication of the original article(Wei et al.2023),it is reported that the“Availability of data and materials”section needs to be updated.The original version was:All data generated or analyzed during this study are included in this published article and its supplemen-tary information files.Requests for materials should be addressed to the corresponding author.

Development of a 32-gene signature using machine learning for accurate prediction of inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic inflammatory condition caused by multiple genetic and environmental factors.Numerous genes are implicated in the etiology of IBD,but the diagnosis of IBD is challenging.Here,XGBoost,a machine learning prediction model,has been used to distinguish IBD from healthy cases following elaborative feature selection.Using combined unsupervised clustering analysis and the XGBoost feature selection method,we successfully identified a 32-gene signature that can predict IBD occurrence in new cohorts with 0.8651 accuracy.The signature shows enrichment in neutrophil extracellular trap formation and cytokine signaling in the immune system.The probability threshold of the XGBoost-based classification model can be adjusted to fit personalized lifestyle and health status.Therefore,this study reveals potential IBD-related biomarkers that facilitate an effective personalized diagnosis of IBD.

The cyclooxygenase-expressing mesenchyme resists intestinal epithelial injury by paracrine signaling

Paracrine signals play pivotal roles in organ homeostasis.Mesenchymal stromal cells(MSCs)play a key role in regulating epithelium homeostasis in the intestine while their paracrine effects are poorly characterized.Here,we identified prostaglandin E2(PGE2)secreted by cyclooxygenase(COX)-expressing MSCs as a vital factor to maintain the intestinal mucosal barrier.We found that MSCs-induced organoid swelling through paracrine effect in vitro,a process due to enhanced water adsorption and is mediated by the COX-PGE2-EP4 axis.To further explore the regulatory effect of this axis on the intestinal epithelial barrier in vivo,we established the conditional knockout mouse model to specifically delete COX in MSCs and found that PGE2 reduction downregulated the gene Muc2 and induced a gastric metaplasia-like phenotype.Moreover,PGE2 defects increased the susceptibility of intestinal epithelium to colitis.Our study uncovers the paracrine signaling of COX-expressing MSCs in intestinal mucosal barrier maintenance,providing a basis for understanding the role of mesenchymal cells in the pathophysiological function of the intestine.

气肿性肾盂肾炎14例诊治分析和治疗策略

目的总结气肿性肾盂肾炎病例的临床表现和诊治策略。方法回顾性分析浙江大学医学院附属邵逸夫医院泌尿外科2011年10月至2020年11月连续收治的14例气肿性肾盂肾炎患者的病例资料。男性3例,女性11例。中位年龄59岁(范围:52~73岁)。病变位于左肾者10例,右肾者4例。出现症状到就诊的中位时间3 d(范围:2~5 d)。所有患者均合并2型糖尿病。14例患者均有发热,均出现脓毒性休克症状。致病菌主要为大肠埃希菌11例和肺炎克雷伯菌3例。CT检查主要表现为患侧肾实质内分叶状或气泡状积气5例、斑点状或条纹状积气者9例、积液3例,肾周组织内积液1例。所有患者均于ICU接受抗休克、抗感染治疗,3例患者单纯行经皮穿刺引流术,3例患者行急诊患侧肾切除术,8例患者先行经皮穿刺引流术,病情稳定后再二期行患侧肾切除术。结果3例死亡,11例存活。中位ICU停留时间6 d(范围:3~11 d)。3例死亡患者中,2例接受经皮穿刺引流术,1例接受急诊肾切除术。11例治愈患者中,1例接受经皮穿刺引流术,10例接受肾切除术(8例先行经皮穿刺引流术)。11例存活患者出院后6个月时随访,2例失访,其余9例血肌酐为(118.4±29.4)μmol/L(范围:89~176μmol/L)。结论对于合并糖尿病、初诊为急性肾盂肾炎的患者,在病情迅速进展、出现脓毒性休克时应考虑气肿性肾盂肾炎的可能。CT检查显示肾脏及肾周感染性病变伴肾实质内积气可明确诊断。在积极抗感染、规范化抗脓毒性休克治疗的基础上,一期先行经皮穿刺引流术,病情稳定后二期行患侧肾切除术可以取得良好的效果。

Intestinal cellular heterogeneity and disease development revealed by single-cell technology

The intestinal epithelium is responsible for food digestion and nutrient absorption and plays a critical role in hormone secretion,microorganism defense,and immune response.These functions depend on the integral single-layered intestinal epithelium,which shows diversified cell constitution and rapid self-renewal and presents powerful regen-eration plasticity after injury.Derailment of homeostasis of the intestine epithelium leads to the development of dis-eases,most commonly including enteritis and colorectal cancer.Therefore,it is important to understand the cellular characterization of the intestinal epithelium at the molecular level and the mechanisms underlying its homeostatic maintenance.Single-cell technologies allow us to gain molecular insights at the single-cell level.In this review,we summarize the single-cell RNA sequencing applications to understand intestinal cell characteristics,spatiotemporal evolution,and intestinal disease development.

Burden of Mental and Substance Use Disorders-China, 1990−2019

Summary What is already known about this topic?Mental and substance use disorders have notable contributions to the disease burden in China.What is added by this report?In China,mental disorders and substance use disorders accounted for 20.29 million and 5.76 million disability-adjusted life years(DALYs)in 2019,respectively;depressive disorders were the leading cause of DALYs.For mental disorders,the numbers of DALYs increased 12.06%from 2000 to 2019 while the standardized rates declined 5.24%;for substance use disorders,both the numbers and standardized rates of DALYs decreased 8.52%and 18.52%,respectively.

National Alveolar Echinococcosis Distribution--China, 2012−2016

What is already known about this topic?Both alveolar echinococcosis(AE)and cystic echinococcosis are endemic in China,among which alveolar echinococcosis has a very high mortality rate.What is added by this report?The survey results showed the prevalence and scope of AE in China and identified high-risk groups including children,monks,herdsmen and illiterate people.At the same time,all the cases found in the survey(more than 90%of the patients did not go to the hospital for diagnosis and treatment before survey)were promptly diagnosed and treated.What are the implications for public health practice?This study provides information for the development of a plan for AE prevention and control and for the implementation of interventions targeted to high-risk populations.

Combined quantitative microscopy on the microstructure and phase evolution in Li1.3Al0.3Ti1.7(PO4)3 ceramics

Lithium aluminum titanium phosphate(LATP)is one of the materials under consideration as an electrolyte in future all-solid-state lithium-ion batteries.In ceramic processing,the presence of secondary phases and porosity play an important role.In a presence of more than one secondary phase and pores,image analysis must tackle the difficulties about distinguishing between these microstructural features.In this study,we study the phase evolution of LATP ceramics sintered at temperatures between 950 and 1100℃by image segmentation based on energy-dispersive X-ray spectroscopy(EDS)elemental maps combined with quantitative analysis of LATP grains.We found aluminum phosphate(AlPO4)and another phosphate phase((Lix)PyOz).The amount of these phases changes with sintering temperature.First,since the grains act as an aluminum source for AlPO4 formation,the aluminum content in the LATP grains decreases.Second,the amount of secondary phase changes from more(Lix)PyOz at 950℃to mainly AlPO4 at 1100℃sintering temperature.We also used scanning electron microscopy(SEM)and confocal laser scanning microscopy(CLSM)to study the evolution of the LATP grains and AlPO4,and LATP grain size increases with sintering temperature.In addition,transmission electron microscopy(TEM)was used for the determination of grain boundary width and to identify the amorphous structure of AlPO4.

Comparing COVID-19 Case Prediction Between ARIMA Model and Compartment Model—China,December 2019–April 2020

Introduction:To compare the performance between the compartment model and the autoregressive integrated moving average(ARIMA)model that were applied to the prediction of new infections during the coronavirus disease 2019(COVID-19)epidemic.Methods:The compartment model and the ARIMA model were established based on the daily cases of new infection reported in China from December 2,2019 to April 8,2020.The goodness of fit of the two models was compared using the coefficient of determination(R2).Results:The compartment model predicts that the number of new cases without a cordon sanitaire,i.e.,a restriction of mobility to prevent spread of disease,will increase exponentially over 10 days starting from January 23,2020,while the ARIMA model shows a linear increase.The calculated R2 of the two models without cordon sanitaire were 0.990 and 0.981.The prediction results of the ARIMA model after February 2,2020 have a large deviation.The R2 of complete transmission process fit of the epidemic for the 2 models were 0.964 and 0.933,respectively.Discussion:The two models fit well at different stages of the epidemic.The predictions of compartment model were more in line with highly contagious transmission characteristics of COVID-19.The accuracy of recent historical data had a large impact on the predictions of the ARIMA model as compared to those of the compartment model.&Joint first authors.

The Health Demands of Designated Drivers-Four Cities,China,2019

Summary What is already known about this topic?The health status of designated drivers is largely associated with road safety,which is a major public health issue.However,few studies have focused on the health demands of designated drivers.What is added by this report?This study investigated the health consciousness,first aid knowledge learning,acceptable ways to acquire health knowledge,and willingness to have physical examinations for designated drivers to provide suggestions for improving their health status.What are the implications for public health practice?The industry and platform should provide scientific and reasonable guidance on healthy lifestyles for designated drivers and implement physical examinations to monitor their health status.

Application of Disability-Adjusted Life Years to Evaluate the Burden and Trend of Tuberculosis — China, 1990–2019

Summary What is already known about this topic?China is a country with a high burden of tuberculosis(TB).However,the evaluation of TB burden is usually based on traditional epidemiological indicators,and disability-adjusted life year(DALY)is rarely applied.What is added by this report?In China,the number of DALYs caused by TB in 2019 was estimated to be 1.36 million,and the agestandardized rate(ASR)was 86.46/100,000.The DALYs of TB decreased significantly from 1990 to 2019,with the largest decline from 2001 to 2010.The burden is higher among men than women,and the highest among the elderly.What are the implications for public health practice?Application of DALYs can reflect the damage in health to China’s residents caused by tuberculosis.In the future,we should strengthen research,monitor years lived with disability(YLDs),and reduce the burden of the elderly and men.Cost-effective analysis based on DALYs should be conducted to provide a scientific basis for decision-making.

Burden of Acute Viral Hepatitis--China,1990−2019

What is already known about this topic?The World Health Organization’s(WHO)Global Health Estimates(GHE)reported that acute hepatitis caused 9,213 deaths and 307,720 person years of disability-adjusted life years(DALYs)in 2016,and acute hepatitis B accounted for 85.81%of all DALYs among acute hepatitis types A,B,C,and E in China.What is added by this report?In China,the percent changes in years lived with disability(YLDs)due to acute hepatitis A,B,and E in groups aged 50–69 years and 70 years or more and in all age groups for acute hepatitis C were increased from 2000 to 2019.What are the implications for public health practices?Effective vaccines,interventions,and treatments are key approaches to achieve the WHO’s goal of reducing new hepatitis infections by 90%and deaths by 65%between 2016 and 2030.

Economic Burden of Malignant Tumors——Yichang City,Hubei Province,China,2019

Summary What is already known about this topic?Malignant tumors are common chronic noncommunicable disease and have caused serious health hazards to residents and heavy economic burden of disease to the society.What is added by this report?This is the first report on the economic burden of multiple types of malignant tumors in Yichang City.In 2019,the direct medical burden of lung cancer in Yichang was the highest,reaching 561.67 million CNY,and the indirect economic burden of lung cancer in Yichang was higher than that of other malignant tumors,costing 326.49 million CNY.

Incidence Tendency Analysis on Type 2 Diabetes in 4 Asian Countries—China,Malaysia,Singapore,and Thailand,1990–2019

Summary What is already known about this topic?Roughly 80%of the global disease burden caused by diabetes comes from low-and-middle income countries,and 60%of diabetics are located in Asia;6 of the top 10 countries with the highest prevalence of diabetes are in Asia.What is added by this report?Compared with 1990,the growth rate of the standardized incidence rate of type 2 diabetes in 2019 in China was significantly lower than that of the entire world,while Malaysia,Singapore.

Professor Jian Lu’s Interdisciplinary Approach to Modeling the COVID-19 Pandemic

Editorial Our new column Insights is an ongoing series of interviews prepared by the China CDC Weekly team with researchers,policymakers,experts,and other leaders that strives to disseminate experiences,knowledge,and perspectives in global and public health with a wider community.At the discretion of the Weekly’s team,these interviews will be written into articles,shared as videos,and/or presented as transcripts to best promote plain-language principles and to ease understanding of non-specialized academic readers.