Progress in the Study of Inflammatory Bowel Disease Patients with Primary Non-Responsiveness

Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.

Role of vascular endothelial growth factor B in nonalcoholic fatty liver disease and its potential value

Nonalcoholic fatty liver disease(NAFLD)refers to fatty liver disease caused by liver injury factors other than alcohol.The disease is characterized by diffuse fat infiltration,including simple steatosis(no inflammatory fat deposition),nonalcoholic fatty hepatitis,liver fibrosis,and so on,which may cause liver cirrhosis,liver failure,and even liver cancer in the later stage of disease progression.At present,the pathogenesis of NAFLD is still being studied.The"two-hit"theory,represented by lipid metabolism disorder and inflammatory reactions,is gradually enriched by the"multiple-hit"theory,which includes multiple factors,such as insulin resistance and adipocyte dysfunction.In recent years,vascular endothelial growth factor B(VEGFB)has been reported to have the potential to regulate lipid metabolism and is expected to become a novel target for ameliorating metabolic diseases,such as obesity and type 2 diabetes.This review summarizes the regulatory role of VEGFB in the onset and development of NAFLD and illustrates its underlying molecular mechanism.In conclusion,the signaling pathway mediated by VEGFB in the liver may provide an innovative approach to the diagnosis and treatment of NAFLD.

Predictors and optimal management of tumor necrosis factor antagonist nonresponse in inflammatory bowel disease:A literature review

Tumor necrosis factor-α(TNF-α)antagonists,the first biologics approved for treating patients with inflammatory bowel disease(IBD),are effective for the induction and maintenance of remission and significantly improving prognosis.However,up to one-third of treated patients show primary nonresponse(PNR)to anti-TNF-αtherapies,and 23%-50%of IBD patients experience loss of response(LOR)to these biologics during subsequent treatment.There is still no recognized predictor for evaluating the efficacy of anti-TNF drugs.This review summarizes the existing predictors of PNR and LOR to anti-TNF in IBD patients.Most predictors remain controversial,and only previous surgical history,disease manifestations,drug concentrations,antidrug antibodies,serum albumin,some biologic markers,and some genetic markers may be potentially predictive.In addition,we also discuss the next steps of treatment for patients with PNR or LOR to TNF antagonists.Therapeutic drug monitoring plays an important role in treatment selection.Dose escalation,combination therapy,switching to a different anti-TNF drug,or switching to a biologic with a different mechanism of action can be selected based on the concentration of the drug and/or antidrug antibodies.

Prevalence and associated factors of obesity in inflammatory bowel disease:A case-control study

BACKGROUND In recent years,an increasing prevalence of obesity in inflammatory bowel disease(IBD)has been observed.Obesity,moreover,has been directly correlated with a more severe clinical course and loss of response to treatment.AIM To assess the prevalence and associated factors of obesity in IBD.METHODS We collected data about IBD disease pattern and activity,drugs and laboratory investigations in our center.Anthropometric measures were retrieved and obesity defined as a body mass index(BMI)>30.Then,we compared characteristics of obese vs non obese patients,and Chi-squared test and Student’s t test were used for discrete and continuous variables,respectively,at univariate analysis.For multivariate analysis,we used binomial logistic regression and estimated odd ratios(OR)and 95%confidence intervals(CI)to ascertain factors associated with obesity.RESULTS We enrolled 807 patients with IBD,either ulcerative colitis(UC)or Crohn’s disease(CD).Four hundred seventy-four patients were male(58.7%);the average age was 46.2±13.2 years;438(54.2%)patients had CD and 369(45.8%)UC.We enrolled 378 controls,who were comparable to IBD group for age,sex,BMI,obesity,diabetes and abdominal circumference,while more smokers and more subjects with hypertension were observed among controls.The prevalence of obesity was 6.9%in IBD and 7.9%in controls(not statistically different;P=0.38).In the comparison of obese IBD patients and obese controls,we did not find any difference regarding diabetes and hypertension prevalence,nor in sex or smoking habits.Obese IBD patients were younger than obese controls(51.2±14.9 years vs 60.7±12.1 years,P=0.03).At univariate analysis,obese IBD were older than normal weight ones(51.2±14.9 vs 44.5±15.8,P=0.002).IBD onset age was earlier in obese population(44.8±13.6 vs 35.6±15.6,P=0.004).We did not detect any difference in disease extension.Obese subjects had consumed more frequently long course of systemic steroids(66.6%vs 12.5%,P=0.02)as well as antibiotics such as metronidazole or ciprofloxacin(71.4%vs 54.7%,P=0.05).No difference about other drugs(biologics,mesalazine or thiopurines)was observed.Disease activity was similar between obese and non obese subjects both for UC and CD.Obese IBD patients suffered more frequently from arterial hypertension,type 2 diabetes,non-alcoholic fatty liver disease.Regarding laboratory investigations,obese IBD patients had higher levels of triglyceridemia,fasting blood glucose,gamma-glutamyl-transpeptidase.On multivariate analysis,however,the only factor that appeared to be independently linked to obesity in IBD was the high abdominal circumference(OR=16.3,95%CI:1.03-250,P=0.04).CONCLUSION Obese IBD patients seem to have features similar to general obese population,and there is no disease-specific factor(disease activity,extension or therapy)that may foster obesity in IBD.

Effect of the Mediterranean Diet on BMI in Middle-Aged Hispanic Women with Pre-Obesity and Obesity Central Washington State

Background: Conclusive evidence has yet to emerge regarding the effectiveness and applicability of the Mediterranean diet on middle-aged Hispanic women, the largest female minority group in the United States who is at-risk of metabolic disorders. Objective: The aim of this study is to evaluate the effect of the Mediterranean diet (MED) on the BMI in middle-aged Hispanic women with pre-obesity and obesity in Central Washington State. Design: A prospective study was performed to determine the effect of Mediterranean diet on the BMI of 67 Hispanic women with pre-obesity and obesity between 45 to 65 years of age in Central Washington State. The study was carried out for eight weeks. Dietary adherence was monitored to ensure consistent results. Results: The proportion of Hispanic women who reported a reduction in BMI was 94%, with a decrease in mean BMI after eight weeks of 2.8 (95% CI: 2.5 to 3.0) and P = 0.02, with an odds ratio of 2.6. Multiple linear regression analysis was used to adjust for age, education, physical activity, and smoking. Conclusion: The reduction in BMI demonstrates that the Mediterranean diet can be a promising, culturally appropriate therapy to address the obesity epidemic that is prevalent among Hispanic women.

Efficacy of a Strategy for Implementing Guidelines for the Control of Cardiovascular Risk in Primary Healthcare

Background: A number of strategies exist for the implementation of clinical practice guides (CPGs). Aim: To assess the efficacy of implementing a cardiovascular risk CPG based on an educational method involving opinion leaders, and the habitual method of dissemination among primary healthcare teams. Design and Setting: Controlled, blinded, community intervention trial randomised by clusters. Methods: 21 primary healthcare centres were randomly assigned to either the intervention arm (n = 11) or the control arm (n = 10). The study subjects were patients aged ≥45 years assigned to the centres. The overall impact of the intervention was measured as the difference between the increase in the proportion of patients whose medical records showed the recording of all the variables necessary to calculate cardiovascular risk in both arms. Analyses were performed with Generalized Lineal Model on an intention-to-treat basis. Results: 917 subjects were included at the beginning of the trial (437 in the intervention arm and 480 in the control arm). 826 subjects were included in the final evaluation (436 in the intervention group and 390 in the control arm). At the end of the trial, the recording of the variables necessary for the calculation of the cardiovascular risk in the intervention group had increased more than in the control group (difference between increases 7.49% (95% CI 4.62 - 10.35)) after adjusting for confounding variables. Conclusions: Compared to the habitual method of dissemination, the implementation of this CPG using an educational method involving opinion leaders, improved the recording of the variables needed to calculate patients’ cardiovascular risk.

Relationship of Body Mass Index, Waist Circumference and Cardiovascular Risk Factors in Chinese Adult

Objective To compare the relative risk of waist circumference （WC） and/or BMI on cardiovascular risk factors. Methods A cross-sectional data of 41 087 adults （19 567 male and 21 520 female） from the 2002 China National Nutrition and Health Survey were examined. According to the obesity definition of WGOC （BMI, 24 kg/m^2 and 28 kg/m^2; WC, male 85 cm and 95 cm for male, 80 cm and 90 cm for female）, the study population were divided into 9 groups. The prevalence and odds ratio （ORs） of cardiovascular disease （CVD） risk factors （hypertension, high fasting plasma glucose and dyslipidemia） were compared among these 9 groups. Stepwise linear regression analyses were used to compare the likelihood of BMI and/or WC on CVD risk factors. Results Both the indexes levels and the odds ratios of CVD risk factors were significantly increased （decreased for HDL-C levels） along with the increase of WC and/or BMI, even when the effect of age, sex, income, education, sedentary activity and dietary factors were adjusted. The variances （R2） in CVD risk factors explained by WC only and BMI only were quite similar, but a little bit larger when WC and BMI were combined. The standard fl was higher of BMI when predicting systolic BP and was higher of WC when predicting TG, TC and HDL. Conclusions BMI and WC had independent effects on CVD risk factors and combination of BMI and WC would be more predictive. Findings from the present study provided substantive evidence for the WGOC recommendation of a combined use of BMI and WC classifications.

Physical activity, obesity and gastroesophageal reflux disease in the general population

AIM: To clarify the association between physical activity and gastroesophageal reflux disease (GERD) in nonobese and obese people. METHODS: A Swedish population-based cross-sectional survey was conducted. Participants aged 40-79 years were randomly selected from the Swedish Registry of the Total Population. Data on physical activity, GERD, body mass index (BMI) and the covariates age, gender, comorbidity, education, sleeping problems, and tobacco smoking were obtained using validated questionnaires. GERD was self-reported and defined as heartburn or regurgitation at least once weekly, and having at least moderate problems from such symptoms. Frequency of physical activity was categorized into three groups: (1) "high" (several times/week); (2) "intermediate" (approximately once weekly); and (3) "low" (1-3 times/mo or less). Analyses were stratified for participants with "normal weight" (BMI < 25 kg/m 2 ), "overweight" (BMI 25 to ≤ 30 kg/m 2 ) and "obese" (BMI > 30 kg/m 2 ). Multivariate logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounding by covariates. RESULTS: Of 6969 eligible and randomly selected individuals, 4910 (70.5%) participated. High frequency of physical activity was reported by 2463 (50%) participants, GERD was identified in 472 (10%) participants, and obesity was found in 680 (14%). There were 226 (5%) individuals with missing information about BMI. Normal weight, overweight and obese participants were similar regarding distribution of gender and tobacco smoking status, while obese participants were on average slightly older, had fewer years of education, more comorbidity, slightly more sleeping problems, lower frequency of physical activity, and higher occurrence of GERD. Among the 2146 normal-weight participants, crude point estimates indicated a decreased risk of GERD among individuals with high frequency of physical activity (OR: 0.59, 95% CI: 0.39-0.89), compared to low frequency of physical activity. However, after adjustment for potential confounding factors, neither intermediate (OR: 1.30, 95% CI: 0.75-2.26) nor high (OR: 0.99, 95% CI: 0.62-1.60) frequency of physical activity was followed by decreased risk of GERD. Sleeping problems and high comorbidity were identified as potential confounders. Among the 1859 overweight participants, crude point estimates indicated no increased or decreased risk of GERD among individuals with intermediate or high frequency of physical activity, compared to low frequency. After adjustment for confounding, neither intermediate (OR: 0.75, 95% CI: 0.46-1.22) nor high frequency of physical activity were followed by increased or decreased risk of GERD compared to low frequency among nonobese participants. Sleeping problems and high comorbidity were identified as potential confounders for overweight participants. In obese individuals, crude ORs were similar to the adjusted ORs and no particular confounding factors were identified. Intermediate frequency of physical activity was associated with a decreased occurrence of GERD compared to low frequency of physical activity (adjusted OR: 0.41, 95% CI: 0.22-0.77). CONCLUSION: Intermediate frequency of physical activity might decrease the risk of GERD among obese individuals, while no influence of physical activity on GERD was found in non-obese people.

Recurrence of autoimmune liver diseases after liver transplantation

Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.

The local mammalian target of rapamycin(mTOR) modulation:a promising strategy to counteract neurodegeneration

Alzheimer’s disease (AD) and the evolution of the “Amyloid Hypothesis”: The primary risk factor for dementia is aging, as the overwhelming majority of individuals who have the disease (~95%) are 65 years old or older, and the rate of development of AD doubles roughly every five years from that age, peaking at a nearly 50% population prevalence by the age of 85. The disease is progressive and irreversible, with an average time course of 8 to 10 years. Regardless of catastrophic forecasts for the next decades, its actual prevalence has huge family and social costs.

Impact of gastroesophageal reflux disease on the quality of life of Polish patients

BACKGROUND Gastro-esophageal reflux disease (GERD) is a serious health and social problem leading to a considerable decrease in the quality of life of patients. Among the risk factors associated with reflux symptoms and that decrease the quality of life are stress, overweight and an increase in body weight. The concept of healthrelated quality of life (HRQL) covers an expanded effect of the disease on a patient’s wellbeing and daily activities and is one of the measures of widely understood quality of life. HRQL is commonly measured using a selfadministered, disease-specific questionnaires. AIM To determine the effect of reflux symptoms, stress and body mass index (BMI) on the quality of life. METHODS The study included 118 patients diagnosed with reflux disease who reported to an outpatient department of gastroenterology or a specialist hospital ward for planned diagnostic tests. Assessment of the level of reflux was based on the frequency of 5 typical of GERD symptoms. HRQL was measured by a 36-item Short Form Health Survey (SF-36) and level of stress using the 10-item Perceived Stress Scale. Multi-variable relationships were analyzed using multiple regression. RESULTS Eleven models of analysis were performed in which the scale of the SF-36 was included as an explained variable. In all models, the same set of explanatory variables: Gender, age, reflux symptoms, stress and BMI, were included. The frequency of GERD symptoms resulted in a decrease in patients’ results according to 6 out of 8 SF-36 scales- except for mental health and vitality scales. Stress resulted in a decrease in patient function in all domains measured using the SF-36. Age resulted in a decrease in physical function and in overall assessment of self-reported state of health. An increasing BMI exerted a negative effect on physical fitness and limitations in functioning resulting from this decrease. CONCLUSION In GERD patients, HRQL is negatively determined by the frequency of reflux symptoms and by stress, furthermore an increasing BMI and age decreases the level of physical function.

Clinical management of inflammatory bowel disease in the organ recipient

There was estimated a higher incidence of de novo inflammatory bowel disease (IBD) after solid organ transplantation than in the general population. The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy. IBD course after liver transplantation (LT) is variable, but about one third of patients may worsen, needing an increase in medical therapy or a colectomy. Active IBD at the time of LT, discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimus-based immunosuppression may be associated with an unfavorable outcome of IBD after LT. Anti-tumor necrosis factor alpha (TNF&#x003b1;) therapy for refractory IBD may be an effective and safe therapeutic option after LT. The little experience of the use of biological therapy in transplanted patients, with concomitant anti-rejection therapy, suggests there be a higher more careful surveillance regarding the risk of infectious diseases, autoimmune diseases, and neoplasms. An increased risk of colorectal cancer (CRC) is present also after LT in IBD patients with primary sclerosing cholangitis (PSC). An annual program of endoscopic surveillance with serial biopsies for CRC is recommended. A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention, but it is used infrequently in the majority of LT centers. About 30% of patients develop multiple IBD recurrence and 20% of patients require a colectomy after renal transplantation. Like in the liver transplantation, anti-TNF&#x003b1; therapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation. A large number of patients are needed to confirm the preliminary observations. Regarding the higher clinical complexity of this subgroup of IBD patients, a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.

Regional variations in cardiovascular risk factors in India:India heart watch

Cardiovascular disease(CVD) is an important cause of mortality and morbidity in India.Mortality statistics and morbidity surveys indicate substantial regional variations in CVD prevalence and mortality rates.Data from the Registrar General of India reported greater ageadjusted cardiovascular mortality in southern and eastern states of the country.Coronary heart disease(CHD) mortality is greater in south India while stroke is more common in the eastern Indian states.CHD prevalence is higher in urban Indian populations while stroke mortality is similar in urban and rural regions.Case-control studies in India have identified that the common major risk factors account for more than 90% of incident myocardial infarctions and stroke.The case-control INTERHEART and INTERSTROKE studies reported that hypertension,lipid abnormalities,smoking,obesity,diabetes,sedentary lifestyle,low fruit and vegetable intake,and psychosocial stress are as important in India as in other populations of the world.Individual studies have reported that there are substantial regional variations in risk factors in India.At a macro-level these regional variations in risk factors explain some of the regional differences in CVD mortality.However,there is need to study the prevalence of multiple cardiovascular risk factors in different regions of India and to correlate them with variations in CVD mortality using a uniform protocol.There is also a need to determine the 'causes of the causes' or fundamental determinants of these risk factors.The India Heart Watch study has been designed to study socioeconomic,anthropometric and biochemical risk factors in urban populations in different regions of the country in order to identify regional differences.

Role of TNFSF15 in the intestinal inflammatory response

Gastrointestinal diseases, specifically Crohn's disease, ulcerative colitis, diverticular disease, and primary biliary cirrhosis are all characterized by complicated inflammation of the digestive tract. Their pathology is multifactorial, and risk factors encompass both genetic and environmental factors. Recent advances in the genetic component of inflammatory bowel diseases(IBDs) have revealed that the tumor necrosis factor superfamily member 15(TNFSF15) contains a number of risk alleles associated not only with IBD but also with other diseases such as diverticular disease and primary biliary cirrhosis. These risk alleles in TNFSF15 and the altered expression of its gene product can serve as the common ground between these disorders by explaining at least some of the underlying processes that lead to a dysregulated immune response and subsequent chronic inflammation. Here, we aim to outline how the TNFSF15 gene is involved in the proliferation and cell fate of different populations of T cells and subsequently in the control of both pro-and anti-inflammatory cytokines. Furthermore, we summarize what is currently known of TNFSF15 control region variants, how they are associated with each mentioned disease, and how these variants can explain the autoimmune pathology of said diseases through altered TNFSF15 expression.

代谢相关脂肪性肝病患者发生肌少症性肥胖的风险因素和预测模型构建

目的:探讨代谢相关脂肪性肝病(MAFLD)患者肌少症性肥胖(SO)发生的危险因素,构建预测模型。方法:回顾性选择2018年6月至2023年6月我院收治的410例MAFLD患者,根据SO检出情况将MAFLD患者分为SO组(32例)和非SO组(378例)。多因素Logistic回归分析MAFLD患者发生SO的危险因素并构建预测模型,通过Hosmer-Lemeshow检验和受试者工作特征(ROC)曲线验证预测模型性能。结果:SO组年龄大于非SO组(P<0.05),男性、糖尿病、Child-Pugh分级C级、每周运动频率3次以下比例高于非SO组(P<0.05),BMI、HbA1C、HOMA-IR、hs-CRP高于非SO组(P<0.05),白蛋白低于非SO组(P<0.05)。年龄偏大、高hs-CRP、高HOMA-IR、Child-Pugh分级C级是MAFLD患者发生SO的危险因素(P<0.05)。预测模型预测MAFLD患者发生SO的曲线下面积为0.829(95%CI=0.783~0.872),Hosmer-Lemeshow检验P>0.05。结论:老龄、炎症、胰岛素抵抗、肝功能是MAFLD患者发生SO的相关因素,基于上述风险因素构建的预测模型具有较高的预测MAFLD患者发生SO的效能。

Long-term results of extensive aortoiliac occlusive disease (EAIOD) treated by endovascular therapy and risk factors for loss of primary patency

Background::Although endovascular therapy has been widely used for focal aortoiliac occlusive disease(AIOD),its performance for extensive AIOD(EAIOD)is not fully evaluated.We aimed to demonstrate the long-term results of EAIOD treated by endovascular therapy and to identify the potential risk factors for the loss of primary patency.Methods::Between January 2008 and June 2018,patients with a clinical diagnosis of the 2007 TransAtlantic Inter-Society Consensus II(TASC II)C and D AIOD lesions who underwent endovascular treatment in our institution were enrolled.Demographic,diagnosis,procedure characteristics,and follow-up information were reviewed.Univariate analysis was used to identify the correlation between the variables and the primary patency.A multivariate logistic regression model was used to identify the independent risk factors associated with primary patency.Five-and 10-year primary and secondary patency,as well as survival rates,were calculated by Kaplan-Meier analysis.Results::A total of 148 patients underwent endovascular treatment in our center.Of these,39.2%were classified as having TASC II C lesions and 60.8%as having TASC II D lesions.The technical success rate was 88.5%.The mean follow-up time was 79.2±29.2 months.Primary and secondary patency was 82.1%and 89.4%at 5 years,and 74.8%and 83.1%at 10 years,respectively.The 5-year survival rate was 84.2%.Compared with patients without loss of primary patency,patients with this condition showed significant differences in age,TASC II classification,infrainguinal lesions,critical limb ischemia(CLI),and smoking.Multivariate logistic regression analysis showed age<61 years(adjusted odds ratio[aOR]:6.47;95%CI:1.47-28.36;P=0.01),CLI(aOR:7.81;95%CI:1.92-31.89;P=0.04),and smoking(aOR:10.15;95%CI:2.79-36.90;P<0.01)were independent risk factors for the loss of primary patency.Conclusions::Endovascular therapy was an effective treatment for EAIOD with encouraging patency and survival rate.Age<61 years,CLI,and smoking were independent risk factors for the loss of primary patency.

基层糖尿病微血管疾病筛查与防治专家共识(2024)

糖尿病微血管疾病(DMiVD)是糖尿病常见的慢性并发症,早期识别及有效干预可以显著提高患者生活质量,改善预后。中国微循环学会糖尿病与微循环专业委员会和中华医学会内分泌学分会基层内分泌代谢病学组组织领域内专家,以2021年版为基础,结合最新研究进展,特别针对基层临床实际需求,修订《基层糖尿病微血管疾病筛查与防治专家共识(2024)》。该共识详尽阐述了DMiVD(糖尿病视网膜病变、糖尿病肾脏病、远端对称性多发性神经病变和糖尿病心肌病)的筛查方法、综合管理及防治策略,明确分级诊疗及转诊流程,强化防治DMiVD重要性,为广大医师特别是基层医生及全科医生提供指导和建议,降低DMiVD的发生率、恶化率以及致残致死率。

巨噬细胞的胞葬作用:肥胖相关代谢性疾病治疗的新靶向

背景:巨噬细胞胞葬作用障碍引起的局部和系统炎症损害与多种肥胖相关代谢性疾病有关,且以胞葬作用为靶向的化合物表现出良好的治疗效果。目的:通过综述肥胖对巨噬细胞胞葬作用各个阶段的影响结果分析肥胖抑制胞葬作用的关键机制,总结以胞葬作用为靶向的化合物治疗代谢性疾病的研究现状,以进一步阐明胞葬作用及其与肥胖相关代谢性疾病的关系,为疾病防治策略提供新思路。方法:以“efferocytosis,metabolism,obesity,obese,atherosclerosis,non-alcoholic steatohepatitis,neurodegeneration,tumor,osteoarthritis,diabetes,compound,medicine,treatment”为英文检索词在PubMed和Web of Science数据库检索英文文献,以“胞葬作用”为中文检索词,在中国知网、万方和维普数据库检索中文文献。经严格筛选最终纳入99篇文献进入综述分析。结果与结论:①参与巨噬细胞胞葬作用“寻我”“食我”过程的因子中含有大量凋亡细胞源性因子,因此“寻我”“食我”过程主要受凋亡细胞调控;参与骨架重组和消化过程的胞葬因子主要来源于巨噬细胞,对巨噬细胞胞葬作用活性具有决定性作用。此结果提示,“寻我”“食我”过程的因子表达水平主要反映细胞凋亡情况,在评价巨噬细胞胞葬作用活性时,选择骨架重组和消化阶段的胞葬因子的表达更具科学性。②肥胖抑制巨噬细胞胞葬作用,但肥胖对多数“寻我”“食我”因子及骨架重组因子具有应激性激活作用,对多数消化因子具有抑制作用。此结果进一步说明,消化阶段对胞葬作用活性的决定性意义,并提示部分研究以“寻我”“食我”胞葬因子表达增加作为胞葬作用增强的依据不可靠;且提示未来在探讨以巨噬细胞胞葬作用为靶向的干预策略时,靶向消化阶段胞葬因子可能更有效。③巨噬细胞胞葬作用激活物对多种代谢性疾病治疗有效,但肿瘤组织巨噬细胞胞葬作用抑制物表现出良好的抗癌效果,说明应根据组织炎症特点合理评价胞葬作用的意义。④胞葬作用是2003年提出的一个较新概念,研究历程较短,胞葬因子复杂,目前关于肥胖对胞葬作用影响的研究仅涉及冰山一角并且大部分处于粗浅水平,对其更深入的机制探讨仍需大量科学实验的进一步验证。

包头地区他汀类药物的使用现状及影响因素研究

目的:了解包头地区不同人群他汀类药物的使用现状,并进行影响因素分析,为制定心脑血管病精准防控策略提供数据参考。方法:2021年6月至2022年9月,采用多阶段整群随机抽样方法,抽取包头地区40岁以上常住居民,调查研究对象一般情况、心脑血管疾病认知水平及他汀使用情况,影响因素采用Logistic回归进行分析。结果:共登记有效调查对象2100例,年龄为(58.7±11.0)岁(40~94)岁,男性占45.1%(n=948)。其中既往有心脑血管疾病(CVD)史占14.2%(298例),无CVD有危险因素人群49.5%(1040例),正常人群36.3%(762例)。包头地区报告使用他汀类药物比例14.8%,三组人群分别为46.3%、14.2%、3.1%。多因素分析结果显示,CVD组中,女性患者服用他汀类药物可能性小;高龄、患有高血压、糖尿病且CVD认知水平高则与他汀使用率呈正相关。CVD危险因素组多因素分析结果提示,高龄、CVD认知水平高,他汀类药物使用可能性大,农村、吸烟、肥胖人群可能性小。正常组人群服用他汀原因占比:自觉应服用>亲友介绍>广告媒体宣传>医生处方。结论:内蒙古包头地区人群在心脑血管病二级预防、一级预防中他汀类药物使用不规范,不同亚组人群中差异较大,且存在正常人群过度用药情况。

原发性胆汁性胆管炎合并代谢相关脂肪性肝病的临床特征及危险因素分析

目的分析原发性胆汁性胆管炎(PBC)合并代谢相关脂肪性肝病(MAFLD)的临床特征及危险因素,探讨两种疾病合并时的相互影响。方法选取2019年1月—2022年12月于昆明医科大学第一附属医院确诊为PBC和MAFLD的患者187例,分为PBC组70例,PBC合并MAFLD组38例,MAFLD组79例。收集病例的一般资料、临床症状、血清学指标、瞬时弹性纤维成像(FibroScan)及非侵入性纤维化指标,分析比较三组间的不同特点。计量资料三组间比较采用单因素方差分析或KruskalWallis H检验;计数资料组间比较使用χ^(2)检验或Fisher精确检验。多因素分析采用二元Logistic回归分析。结果三组在性别、年龄、身高、体质量、BMI、自身免疫性疾病病史方面差异均有统计学意义(P值均<0.05)。PBC合并MAFLD组以女性患者多见(89.5%),平均年龄为(57.26±12.72)岁,BMI为(23.35±3.70)kg/m2;PBC组中自身免疫性疾病病史检出率为25.7%(18例)。三组乏力、纳差、瘙痒、黄疸、静脉曲张、腹水、脾大发生率比较,差异均有统计学意义(P值均<0.05)。PBC合并MAFLD组患者常见的症状为乏力、纳差、腹痛、腹胀,分别为18例(47.4%)、15例(39.5%)、14例(36.8%)、16例(42.1%);MAFLD组患者常见的症状为腹痛、腹胀,分别为34例(43%)、32例(40.5%);PBC组患者常见的症状及并发症为乏力、纳差、黄疸、腹痛、腹胀、静脉曲张、腹水、脾大,分别为37例(52.9%)、25例(35.7%)、25例(35.7%)、18例(25.7%)、25例(35.7%)、19例(27.9%)、23例(32.9%)、44例(62.9%)。PBC合并MAFLD组的CAP值高于PBC组(P<0.05);PBC组的LSM值、APRI、FIB-4均高于MAFLD组(P值均<0.05)。将不存在多重共线性的因素纳入回归分析,以PBC组为参照组,FIB-4(OR=0.218,95%CI:0.069~0.633)、自身免疫性疾病病史(OR=0.229,95%CI:0.067~0.810)为PBC合并MAFLD的独立影响因素(P值均<0.05);以MAFLD组为参照组,ALT(OR=0.157,95%CI:0.025~1.000)、TBil(OR=0.995,95%CI:0.990~0.999)为PBC合并MAFLD的独立影响因素(P值均<0.05)。结论PBC合并MAFLD临床表现并不特异,但PBC患者的临床表现更为严重,且肝功能失代偿发生率更高。两种疾病合并不一定会加重PBC的疾病进展。