Cancer vaccines based on tumor cell components have shown promising results in animal and clinical studies. The vaccine system contains abundant tumor antigen components, which can activate the immune system by antigens. However, their efficacy has been limited by the inability of antigens delivery, which are the core components of vaccines, further fail to be presented and activation of effective cells. Nanotechnology offers a novel platform to enhance the immunogenicity of tumor-associated antigens and deliver them to antigen-presenting cells (APCs) more efficiently. In addition, nanotreatment of tumor cells derivate active ingredients could also help improve the effectiveness of cancer vaccines. In this review, we summarize recent advances in the development of cancer vaccines by the combination of nanotechnology and tumor-based ingredients, including liposomes, polymeric nanoparticles, metallic nanoparticles, virus-like particles and tumor cells membrane, tumor lysate, and specific tumor antigens. These nanovaccines have been designed to increase antigen uptake, prolong antigen presentation, and modulate immune responses through codelivery of immunostimulatory agents. We also further discuss challenges and opportunities in the clinical translation of these nanovaccines.

BackgroundEvidence from observational studies suggests that chronic hepatitis B (CHB) is associated with cardiovascular disease (CVD). However, results have been inconsistent and causality remains to be established. We utilized two-sample Mendelian randomization (MR) to investigate potential causal associations between CHB and CVD, including atherosclerosis, coronary heart disease, hypertension, and ischemic stroke.MethodsThe analysis was conducted through genome-wide association studies (GWAS), considering chronic hepatitis B as the exposure and cardiovascular disease as the endpoint. The primary method for evaluating causality in this analysis was the inverse-variance weighted (IVW) technique. Additionally, we employed the weighted median, MR-Egger regression, weighted mode, and simple mode methods for supplementary analyses. Finally, heterogeneity tests, sensitivity analyses, and multiple effects analyses were conducted.ResultsIn a random-effects IVW analysis, we found that genetic susceptibility to chronic hepatitis B was associated with an increased risk of atherosclerosis [OR = 1.048, 95% CI (1.022–1.075), P = 3.08E-04], as well as an increased risk of coronary heart disease [OR = 1.039, 95% CI (1.006–1.072), P = 0.020]. However, it was found to be inversely correlated with ischemic stroke risk [OR = 0.972, 95% CI (0.957–0.988), P = 4.13E-04]. There was no evidence that chronic hepatitis B was associated with hypertension [OR = 1.021, 95% CI (0.994–1.049), P = 0.121].ConclusionOur research indicates that chronic hepatitis B has a correlation with an elevated risk of developing atherosclerosis and coronary heart disease, while it is associated with a decreased risk of experiencing an ischemic stroke.

The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion.

Abstract The observational association between circulating metabolites and non-alcoholic fatty liver disease (NAFLD) has been somewhat demonstrated. However, it is unclear whether there is a causal relationship for this association. In this study, we used a two-sample bidirectional MR analysis approach to assess the association between 1,400 blood metabolites and NAFLD. Causality was estimated using the inverse variance weighted (IVW) method, and sensitivity analyses were applied after performing false discovery rate (FDR) correction to assess heterogeneity and pleiotropy. In addition, we performed linkage disequilibrium regression (LDSC) analysis, confounder analysis and metabolic pathway analysis. Corrected for FDR, we identified seven metabolites suggestively associated with NAFLD, including imidazole lactate levels (OR = 0.90,95% CI = 0.85–0.95,P = 0.0004), cysteine-glutathione disulfide levels (OR = 0.80, 95%CI = 0.72–0.89,P = 0.0001), 3-indoleglyoxylic acid levels(OR = 0.87,95%CI = 0.80–0.94,P = 0.0009), lithocholate sulfate (1) levels (OR = 1.18,95%CI = 1.07–1.30, P = 0.006), bilirubin degradation product, C17H18N2O4 (2) levels (OR = 1.14,95%CI = 1.07–1.21,P = 4.02E-05), bilirubin degradation product, C17H18N2O4 (3) levels (OR = 1.13, 95%CI = 1.06–1.21,P = 0.0001), and biliverdin levels (OR = 1.12, 95% CI = 1.05–1.18, P = 0.023). This study provides evidence support for the causal effect of seven metabolites on NAFLD, and provides new perspectives for combining genomics and metabolomics to explore the biological mechanisms of NAFLD.

Abstract Mitochondria-related proteins (MRPs) and chronic liver diseases have been linked in various studies, although their causal relationship has not been elucidated. In this study, we investigated the causal associations between MRPs and non-alcoholic fatty liver disease (NALFD), liver cirrhosis and hepatocellular carcinoma (HCC) by two-sample bidirectional Mendelian randomisation(MR) analysis.The random-effect Inverse variance weighted (IVW) is the primary analysis for causality analysis while MR-Egger and Weighted Median (WM) as complementary analyses. Cochran Q test, MR-Egger intercept test, MR-PRESSO and leave-one-out analysis were used for sensitivity analyses. In addition, we performed bonferroni correction,multivariable MR analysis(MVMR),reverse causality detection and protein–protein interaction(PPI) network to enrich the results of this study.After rigorous genetic variant selection, IVW, sensitivity analysis, 3 genetically determined MRPs were significantly associated with NAFLD [MRPL33 (OR: 1.06, 95% CI: 1.00-1.11, p = 0.0284), MRPL34 (OR: 0.88, 95% CI: 0.78–0.98, p = 0.0294) and FARS2 (OR : 0.90, 95% CI: 0.84–0.97, p = 0.0120)], 2 MRPs were significantly associated with liver cirrhosis[MICU1 (OR: 1.11, 95% CI: 1.00-1.22, p = 0.0337) and NUDT8 (OR: 1.16, 95% CI: 1.03–1.30, p = 0.0096)], and 4 MRPs were significantly correlated with HCC [MRPL32 (OR: 0.62, 95% CI: 0.39–0.99, p = 0. 0492), MRPL33 (OR:1.29, 95% CI: 1.07–1.55, p = 0.0063), SCO1 (OR:0.56, 95% CI. 0.38–0.83, p = 0.0036) and SIRT5 (OR:0.71, 95% CI: 0.53–0.96, p = 0.0283)].Our findings provide a new perspective on the exploration of the underlying mechanisms of chronic liver diseases. However, further studies are still needed to explore the mechanisms of possible potential causal associations between MRPs and chronic liver diseases.

Polycythemia vera (PV) and non-cirrhotic portal hypertension (NCPH) are relatively independent diseases, and few studies have linked them. However, in clinical settings, there may be a causal relationship. The aim of the present study was to analyze the clinical data of five patients with portal hypertension caused by PV and summarize the characteristics of PV with portal hypertension, to enhance the knowledge of this disease. The clinical data of five patients with PV and portal hypertension treated at Beijing You'an Hospital (Beijing, China) from January 2010 to March 2022 were retrospectively collected. The characteristics of these patients were then summarized and analyzed, including general information, laboratory tests, imaging and gastroscopy data. Overall, four patients were diagnosed with PV earlier compared with those with NCPH (ranging between days and years), whereas one patient was diagnosed with NCPH at the time of PV diagnosis. These four patients had blood cell elevations of 2-3 categories (red blood cells, white blood cells or platelets). The Child classification of liver functions in all five patients were found to be grades A-B. All five patients had splenomegaly, where three patients had portal vein thrombosis and cavernous degeneration. In addition, four patients had moderate or severe esophageal varices. In conclusion, to the best of our knowledge, this was the first case series of NCPH caused by PV. Among the patients, it was revealed that: i) NCPH caused by PV had milder liver function damage compared with cirrhosis-induced portal hypertension; ii) splenomegaly, ascites and esophageal varicose veins were prominent symptoms of NCPH caused by PV; iii) If PV is diagnosed, esophagogastroduodenoscopy should be performed as early as possible and regularly, where primary prevention measures for esophageal variceal hemorrhage are recommended; and iv) patients with PV with portal hypertension are at risk of thrombosis and bleeding, but it remains to be determined whether early antithrombotic therapy can reduce complications.

Background: Coronavirus disease (COVID-19) caused a pandemic in January 2020. Its mutations and high infectivity have serious health and economic implications. This study aimed to clarify the short-term symptoms, duration, and influencing factors in people recovering from COVID-19 after China’s dynamic zero-COVID-19 policy was implemented in December, 2022.Methods: We included data from a large-scale online survey conducted in China between January 14 and February 1, 2023. Participants were individuals of all ages. Chi-squared tests and multivariate logistic regression analyses were performed to identify factors associated with different symptoms.Findings: Overall, 21,012 patients from seven regions of China were included in this study, with 71·22%. being female. For most patients, the period from symptom onset to a negative nucleic acid test result was ≤10 days (72·33%). The distribution of symptoms in different systems varied at different times, with respiratory (1–4 weeks) and psycho-cardiology (5–8 weeks) symptoms being the most common. Multivariate analysis identified male sex, no comorbidity, and living in northeast and northwest China (compared with central China) as independent factors associated with less likelihood of having symptoms, while age (41–60 years) was deemed a possible risk factor (compared with 18–40 years).Interpretation: Short-term symptoms of the respiratory and psycho-cardiology systems were most common after COVID-19 recovery. Sex, age, geographical region, and comorbidities were potential influencing factors for the development of short-term symptoms.Funding: The Youth Qi-Huang Scholarship was received from the State Administration of Traditional Chinese medicine (Chinese Traditional Medicine Scholarship [2020] No. 218) (YL2202020414).Declaration of Interest: All other authors declare no competing interests.Ethical Approval: The Ethics Committee at Tianjin University of Traditional Chinese Medicine provided institutional review board approval (approval number: TJUTCM-EC20230002). Informed consent was discussed as part of the introduction to the questionnaire; the introduction mentioned the survey objective, initiatives, content, confidentiality of information, and the time required to fill out the questionnaire. After acceptance of the above, patients could voluntarily answer and submit their questionnaires.

张某,男,65岁,主因"肝病史13年,神智改变3 d"于2021年6月2日 就诊于北京佑安医院.患者2008年体检时发现肝硬化,未予重视及治疗.2010年因便血于宣武医院止血对症治疗后好转出院.2014年因上消化道出血于解放军第三○一医院行胃镜下硬化剂治疗,后定期复查.

目的 基于文本挖掘技术和生物医学数据库对新型冠状病毒肺炎(COVID-19)相关文献进行数据挖掘分析,探究COVID-19及其主要症状发热、咳嗽、呼吸障碍相关基因靶点,筛选潜在有效的化学药和中药.方法 使用GenCLiP 3网站获取COVID-19和其主要症状咳嗽、发热、呼吸障碍共4个关键词的共有靶点,在METASCAPE数据库中对其进行基因本体(GO)和通路富集分析,再利用String数据库和Cytoscape软件构建共有靶点的蛋白质相互作用网络,筛选获得核心基因,运用DGIdb数据库、SymMap数据库针对核心基因进行中西医治疗药物预测.结果 获得COVID-19及其主要症状共有基因靶点28个,其中有IL2、IL1B、CCL2等核心基因16个,使用DGIdb数据库筛选获得与16个关键靶点相互作用的化学药包括沙利度胺、来氟米特、环孢素等28种,中药包括虎杖、黄芪、芦荟等70味.结论 COVID-19及其主要症状的病理机制可能和CD4、KNG1、VEGFA等28个共有基因相关,可能通过介导TNF、IL-17等信号通路参与COVID-19病理过程.潜在有效药物可能通过作用相关靶点通路起到治疗COVID-19的作用.

目的 介绍一种稳定可靠的肝组织上和体外培养的大鼠肝窦内皮细胞(liver sinusoidal endothelial cells,LSECs)的扫描电子显微镜样本制作方法,以便于形态学方面的研究.方法 采用戊二醛、单宁酸、锇酸三步固定;酒精梯度脱水;六甲基二硅氮烷置换;离子喷镀导电处理.结果 扫描电子显微镜下可观察到肝组织上及体外培养的大鼠LSECs的精细结构.结论 该实验方法可作为可靠的大鼠LSECs扫描电子显微镜样本的制作方法.

文章通过分析两种版本《辅行诀脏腑用药法要》对"朮"记载的差异,探讨"朮"的真正所指药物.结合校勘本原文分析"术"的具体应用,从具体药物中分析《辅行诀脏腑用药法要》的用药思路;结合"朮"的历史变革,讨论"朮"的临床应用沿革.

BACKGROUND:Acute gouty arthritis (AGA) is a common arthritis disease, with the characteristics of acute onset, severe condition, and poor prognosis. The conventional treatments have shown certain curative effects but are accompanied with many adverse reactions. The combination of orally taken Qinpi Tongfeng Formula (QPTFF) and bloodletting therapy could effectively alleviate arthralgia and joint swelling in AGA patients. However, there is a lack of high-quality randomized controlled trials (RCTs) to evaluate the clinical efficacy and safety of the combined therapy against AGA.METHODS:This is a prospective, randomized, parallel controlled trial conducted in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine to explore the efficacy and safety of QPTFF combined with bloodletting therapy in the treatment of AGA. Eighty-six AGA patients meeting the inclusion and exclusion criteria will be randomly divided into the treatment group and control group in a 1 : 1 ratio using a randomization table. The investigators and the patients will not be blinded, while the outcome assessors and statisticians will be blinded to the allocation. Patients in the treatment group will take QPTFF and bloodletting therapy simultaneously, while patients in the control group will be instructed to orally take colchicine tablets. The primary outcome is the total effective rate, and the secondary outcomes are the pain changes after the first treatment, pain scores, complete pain relief time, joint symptom scores, TCM syndrome score, and laboratory test. SPSS22.0 will be used for statistical analysis. Discussion. This study will evaluate the clinical efficacy and safety of QPTFF combined with bloodletting therapy in the treatment of AGA, and the results of this study will provide reliable clinical evidence for the clinical use of QPTFF combined with bloodletting in the treatment of AGA. The trial is registered with ChiCTR2100048836.

目的 观察柴苓汤结合传统吞咽及神经肌肉电刺激疗法(NMES)治疗缺血性脑卒中后吞咽障碍的临床效果.方法 选取2019年7月至2020年6月于浙江省湖州市第一人民医院治疗的100例缺血性脑卒中后吞咽障碍患者,根据随机数字表法将其分成对照组和治疗组,各50例.对照组予以脑卒中常规药物,同时采用传统吞咽治疗和NMES修复吞咽功能;治疗组除上述治疗外,加用柴苓汤口服或鼻饲.两组均治疗4周,治疗前后均通过洼田饮水试验、美国国立卫生研究院卒中量表(NIHSS)及电视透视吞咽功能检查(VFSS)对比临床疗效.结果 治疗组临床总有效率高于对照组,差异有统计学意义(P<0.05).治疗后,两组洼田饮水试验评分、NIHSS评分低于治疗前,VFSS评分高于治疗前,且治疗组洼田饮水试验评分、NIHSS评分低于对照组,VFSS评分高于对照组,差异有统计学意义(P<0.05).结论 柴苓汤结合传统吞咽疗法和NMES治疗缺血性脑卒中后吞咽障碍对患者吞咽功能的修复具有良好效果,值得临床推广.

吕文良教授多年深入临床分析慢性乙型病毒性肝炎的病因病机,认为其病理性质为本虚标实,尤重视益气佐其正气,同时佐以清热、利湿、解毒等法.吕文良教授针对病机用黄芪、茵陈、黄芩、黄连、黄柏等为主药,加减治疗多种慢性肝病,疗效显著,本文对其治验进行初步探析.

吕文良教授认为慢性乙型肝炎(Chronic hepatitis B,CHB)因疫毒内伏,其基本病机为肝脾肾失调、湿热内蕴、毒损肝络,治疗过程中强调清热利湿、祛邪解毒应贯穿疾病的始终,扶助正气是疾病治疗的关键;同时以治未病思想为指导,截断病势,重视整体调养,尤重调神.辨病与辨证相结合治疗慢性乙型肝炎,疗效显著,并附典型医案一则.

基于吕文良教授学术思想,探讨"三黄"组合思路及其在肝病中的应用.三黄组合由黄芩、黄连、黄柏组成,广泛应用于病毒性肝炎、肝纤维化、脂肪性肝病、药物性肝病、酒精性肝病、免疫性肝病、胆汁淤积性肝病、肝癌等诸多肝脏疾病中.吕文良教授认为湿热内蕴、毒邪内积是肝病的关键病机之一,湿热、毒邪常常相互影响、互为因果,无论病程长短,湿热、毒邪始终贯穿于其中."三黄"味苦、气寒,具有清热燥湿,直折邪毒之功,靶向性强,兼顾三焦,药精效著,不论何种肝脏疾病或同一病种的不同阶段,凡符合三黄病机,皆可应用,拓宽了三黄组合的适用范围.并结合现代研究,为三黄组合思路在肝病中的应用提供了客观依据.

Vitamins were closely associated with non-alcoholic fatty liver disease (NAFLD) development, but no study had explored the association of serum multivitamin levels with NAFLD risk. We assessed the association between serum levels of both single-vitamin and multivitamins (VA, VB6, VB9, VB12, VC, VD, and VE) and the risk of NAFLD, using the database of National Health and Nutrition Examination Survey (NHANES) (cycles 2003–2004 and 2005–2006). We employed multivariable logistic regression and weighted quantile sum (WQS) regression models to explore the association of serum multivitamin levels with NAFLD. Among all 2,294 participants, 969 participants with NAFLD were more likely to be male, older, less educated, or have hypertension/high cholesterol/diabetes. After adjustment of covariates, serum VC/VD/VB6/VB9 levels were negatively correlated with NAFLD risk, while serum VA/VE levels were positively correlated with NAFLD risk. In the WQS model, elevated serum VA/VE levels and lowered serum VC/VD/VB6 levels were linearly associated with increased NAFLD risk. There was a non-linear relationship between serum VB9/VB12 levels and NAFLD risk. There were evident associations between serum multivitamin levels and reduced NAFLD risk, which was mainly driven by VD/VB9/VC. In conclusion, our findings suggested that serum multivitamin levels were significantly associated with the risk of NAFLD.

原发性肝癌是我国最常见的恶性肿瘤之一,死亡率高.具有起病隐匿、发展迅速、恶性程度高、治疗难度大、预后差等临床特点.我国为世界肝癌高发区域,每年约有38.3 万人死于原发性肝癌[1],5年相对生存率仅为12.1％[2],严重威胁人民生命健康.祖国医学典籍中并未发现肝癌的病名诊断,多以其症状或病机来命名,肝癌多归属于于中医"肝积""积证""积聚"等疾病范畴.

The modern Gastroenterology have witnessed an essential stride since Helicobacter pylori was first found in the stomach and then its pathogenic effect was discovered. According to the researches conducted during the nearly 40 years, it has been found that this bacterium is associated with a natural history of many upper gastrointestinal diseases. Epidemiological data show an increased incidence of autoimmune disorders with or after infection with specific microorganisms. The researches have revealed that H. pylori is a potential trigger of gastric autoimmunity, and it may be associated with other autoimmune diseases, both innate and acquired. This paper reviews the current support or opposition about H. pylori as the role of potential triggers of autoimmune diseases, including inflammatory bowel disease, autoimmune thyroiditis, type 1 diabetes mellitus, autoimmune liver diseases, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, as well as Sjogren’s syndrome, chronic urticaria and psoriasis, and tried to explain the possible mechanisms.

目的:通过"中医传承辅助平台系统(V 2.5)",探讨中药灌肠治疗肝性脑病的用药规律,为中药灌肠治疗肝性脑病提供理论基础.方法:计算机检索1999年1月1日至2020年6月30日使用中药灌肠治疗肝性脑病的中文文献,建立数据库并对数据进行标准化处理,通过关联规律、复杂系统熵聚类等无监督数据挖掘方法,对中药灌肠治疗肝性脑病的处方进行分析.结果:对筛选出的112首处方进行分析,共涉及96味中药,使用频次前20味的有大黄、厚朴、枳实、乌梅、石菖蒲等;挖掘出处方核心药物7味,包括大黄、厚朴、枳实、乌梅、芒硝、赤芍、石菖蒲;并推演出3首新处方.结论:中药灌肠治疗肝性脑病用药精简,以承气汤类药物加减化裁为主,适时加用凉血解毒类药物可以更好地改善患者症状,为今后临床中药灌肠治疗肝性脑病患者提供些许思路与经验.