Background:Cathepsins are pivotal regulators of critical physiological processes implicated in cancer, rheumatic disorders, and inflammatory conditions. Objectives:This study employed Mendelian randomization (MR) to evaluate causal relationships between cathepsins and ankylosing spondylitis (AS). Design:A retrospective study. Methods:Single nucleotide polymorphism data of cathepsins were obtained from the INTERVAL study, and AS data were obtained from the FinnGen database. Inverse variance weighting was used as the primary method to assess the causal relationship described above. Cochran's Q test, MR Egger intercept test, MR-PRESSO, and leave-one-out method were used to analyze study sensitivity, heterogeneity, and pleiotropy. Results:In the forward MR analysis, inverse variance weighted results indicated that higher cathepsin S might be associated with an increased risk of AS (inverse-variance weighting, odds ratio = 1.08, 95% confidence interval = 1.00-1.16, p = 0.047). MR-Egger intercept test and Cochran's Q test did not detect significant heterogeneity or horizontal pleiotropy of instrumental variables. The leave-one-out method confirmed the reliability of causality. The reverse MR analysis found no significant causal relationship between cathepsins and AS. Conclusion:Our MR analysis results suggest a potential causal relationship between cathepsin S and AS. Further studies on the pathogenesis of cathepsin-mediated AS may provide new insights into the prevention and treatment of AS.

The thyroid gland is the largest endocrine organ in the human body, and alterations in its homeostasis may lead to the development of thyroid diseases. The role of essential metals such as iron (Fe), zinc (Zn), and copper (Cu) in the pathogenesis of thyroid diseases has been widely discussed, but the research results are inconsistent. In addition, the therapeutic role of these essential metal elements in patients with thyroid diseases has been significantly underestimated in the clinical practice. A disturbance in the balance of these essential metals will affect thyroid homeostasis in a variety of ways. This article synthesizes current evidence on the effects of essential metal elements (Fe, Zn, and Cu) on a variety of thyroid diseases, such as hypothyroidism, autoimmune thyroid diseases (AITD), and thyroid cancer. It will provide essential metal element-related clues for the development of therapeutic strategies and pathophysiologic studies of thyroid diseases.

This study aims to assess the predictive value of dietary antioxidants in diabetes-cancer comorbidity using interpretable machine learning (ML) models and to identify key clinical factors. Data were sourced from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 2017-2018 cycles, including 44 dietary antioxidants, as well as demographic, lifestyle, and health-related features. 8 ML models (Random Forest, light Gradient Boosting Machines [LightGBM], Logistic Regression, Decision Tree, Multilayer Perceptron, Naïve Bayes, Kernel k-Nearest Neighbors, and Support Vector Machine with Radial Basis Function) were trained, with preprocessing steps for multicollinearity, class imbalance (SMOTE), and data normalization. Model performance was evaluated using AUC, accuracy, Brier scores, and calibration plots. SHapley Additive exPlanations (SHAP) values were applied to interpret feature importance. Data from 8644 participants were analyzed, including 272 individuals with confirmed diabetes-cancer comorbidity. After removing collinear features, the ML model included 30 dietary antioxidant features and 10 baseline features. The Random Forest model achieved optimal performance (AUC = 0.996, accuracy = 0.978, brier score = 0.0241), followed by LightGBM (AUC = 0.993). SHAP analysis revealed that while advanced age, cardiovascular disease, and hypertension were the primary drivers of comorbidity probability, dietary antioxidants are also influential factors. Specifically, polyphenols (daidzein, malvidin, pelargonidin, cyanidin) and essential minerals (magnesium) emerged as the most influential nutritional features. The high accuracy of the Random Forest and LightGBM models underscores their clinical utility in risk stratification for diabetes-cancer comorbidity. While advancing age and cardiometabolic dysfunction primarily drives the probability of diabetes-cancer comorbidity. This study establishes dietary antioxidants, particularly polyphenols such as daidzein and malvidin, as predictive factors for diabetes-cancer comorbidity.

The pituitary gland is a very important endocrine gland in the human body. It secretes and releases many hormones crucial for controlling physiological processes, such as energy metabolism, human growth and development, and reproduction. The renin-angiotensin-aldosterone system regulates water and salt homeostasis, controlling blood pressure. Since the discovery of the renin-angiotensin-aldosterone system, exploring and studying its role in pathophysiology has never stopped, and patients have benefited from drug-based and clinical studies. This review focuses on the effects of the pituitary-target gland axis (pituitary-thyroid axis, pituitary-adrenal axis, pituitary-growth hormone axis, pituitary-gonadal axis) and some hormones secreted and stored by the pituitary gland on the RAAS. While considering that SARS-CoV-2 reinfection still occurs, we aim to provide new insights into water-electrolyte balance and blood pressure regulation.

The incidence of papillary thyroid carcinoma (PTC) has been increasing, and thermal ablation has emerged as a minimally invasive alternative to surgery for low-risk cases. However, post-ablation tumor progression remains a significant clinical challenge. This review synthesizes existing literature on tumor progression after thermal ablation for PTC, analyzing potential causes and evaluating preventive strategies at different diagnostic and treatment stages. Current research reports indicate that the probability of disease progression following thermal ablation for PTMC ranges from 1.25 to 7.7

Purpose: We aimed to verify the impact of functional remediation (FR) on serum brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) levels, to explore the biomechanism of FR intervention in patients with euthymic bipolar disorder (BD). Patients and Methods: This is a randomized controlled, 12-week intervention study with participants randomized into the FR group (n=39) and the treatment as usual group (TAU, n=42) at the 11 ratio. 17-Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to assess affective symptoms and cognitive functioning both at baseline and week 12, respectively. Meanwhile, we collected blood samples (10 milliliters) from all participants for determination of serum BDNF/ TrkB levels both at baseline and week 12. After baseline assessment, all participants received FR or TAU treatments, respectively. Results: Our results showed significant decreasing in HDRS-17 and YMRS scores, increasing in serum BDNF and TrkB levels in both groups over 12 weeks (all p's< 0.05). There were no group differences in the HDRS-17 and YMRS scores (all p's> 0.05), but the FR group showed greater increasing in serum BDNF and TrkB levels than those in the TAU group (all p's< 0.05). In terms of cognition, the change in serum BDNF levels was negatively correlated with changes in Mazes test, and the improved TrKB levels were associated with improved Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) in the FR group (all p's< 0.05). Conclusion: The changes in serum BDNF and TrkB levels may be implicated in the mechanisms underlying FR intervention in euthymic patients with BD. Limitation: A longer follow-up period than 12 weeks and set up healthy controls may make the results more convincing, and the sample size of this study is still insufficient.

ObjectivePrevious observational studies have suggested an association between gut microbiota and diabetic neuropathy (DN). However, confounding factors and reverse causality make the causal relationship between gut microbiota and DN uncertain. We aimed to investigate the interactive causal relationships between the abundance of gut microbiota and DN.MethodsWe conducted a Mendelian randomization (MR) analysis to examine the causal relationship between gut microbiota and DN. Genomic data on gut microbiota at the genus level were obtained from the MiBioGen Consortium, including 18,340 individuals of European descent. Data on diabetic polyneuropathy (DPN) were obtained from the FinnGen Consortium, which included 1,048 cases and 374,434 controls, while data on diabetic autonomic neuropathy (DAN) were also obtained from the FinnGen Consortium, including 111 cases and 374,434 controls. Causal effects were primarily estimated using inverse variance weighted (IVW) analysis, supplemented with four validation methods, and additional sensitivity analyses to assess the pleiotropy, heterogeneity, and robustness of instrumental variables.ResultsThe IVW analysis indicated that Prevotella 9 had a protective effect on DPN (OR = 0.715, 95% CI: 0.521-0.982, P = 0.038), and Bacteroides also showed a protective effect (OR = 0.602, 95% CI: 0.364-0.996, P = 0.048). On the other hand, Ruminococcus 2 had a promoting effect on DPN (OR = 1.449, 95% CI: 1.008-2.083, P = 0.045). Blautia (OR = 0.161, 95% CI: 0.035-0.733, P = 0.018), Clostridium innocuum group (OR = 3.033, 95% CI: 1.379-6.672, P = 0.006), and Howardella (OR = 2.595, 95% CI: 1.074-6.269, P = 0.034) were causally associated with DAN in the IVW analysis, with no evidence of heterogeneity or pleiotropy. Sensitivity analyses showed no significant pleiotropy or heterogeneity.ConclusionOur study identified a causal relationship between gut microbiota and the increased or decreased risk of diabetic neuropathy. These findings underscore the importance of adopting a comprehensive approach that combines gut microbiota modulation with other therapeutic interventions in the management of diabetic neuropathy.

Abnormal glucose metabolism is a common disease of the endocrine system. The effects of drugs on glucose metabolism have been reported frequently in recent years, and since abnormal glucose metabolism increases the risk of microvascular and macrovascular complications, metabolic disorders, and infection, clinicians need to pay close attention to these effects. A variety of common drugs can affect glucose metabolism and have different mechanisms of action. Hypertension is a common chronic cardiovascular disease that requires long-term medication. Studies have shown that various antihypertensive drugs also have an impact on glucose metabolism. Among them, α-receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers can improve insulin resistance, while β-receptor blockers, thiazides and loop diuretics can impair glucose metabolism. The aim of this review was to discuss the mechanisms underlying the effects of various antihypertensive drugs on glucose metabolism in order to provide reference information for rational clinical drug use.

Background: Early detection and diagnosis are important crucial to prevent life-threatening acute attacks in patients with acute intermittent porphyria (AIP). We aim to provide comprehensive data on the clinical and hydroxymethylbilane synthase (HMBS) gene variant characteristics and genotype-phenotype association of Chinese patients with AIP in order to improve clinicians’ knowledge of AIP and reduce misdiagnosis and mistaken treatment.Methods: We searched the literature on Chinese patients with AIP in PubMed, Web of Science, Wiley Online Library, ScienceDirect and Chinese literature databases up to August 2023 in our analysis to explore the clinical and HMBS gene variant characteristics of Chinese patients with AIP.Results: A total of 41 original articles associated with Chinese AIP patients were included for analysis: 97 variants were detected in 160 unrelated families, including 35 missense, 29 frameshift, 24 splicing and 9 nonsense variants, with c.517C>T being the most common variant. Clinical data were reported in 77 of 160 patients: Most of them were female (67/77) and the age was 28.8 ± 9.9 years. The most common symptom was abdominal pain (73/77, 94.8%), followed by central nervous system symptoms (45/77, 58.4%). 13.0% (10/77) of patients experienced psychiatric symptoms. Hyponatremia was the most common electrolyte abnormality (42/77). 31 patients received carbohydrate loading therapy, and 30 of them were improved. 6 patients were treated with carbohydrate loading combined with hemin therapy and 5 eventually improved. All variants causing premature stop codons, frameshifts or enzyme activity center may experience more severe clinical phenotypes such as seizures, respiratory paralysis, intracranial hemorrhage disorder or respiratory failure.Conclusion: The most common presenting symptom in Chinese AIP patients was abdominal pain, followed by central nervous system symptoms. The HMBS gene analysis in Chinese AIP patients revealed that the heterogeneity is strong and the most common variant was missense mutation, with c.517C>T being the most common variant. The genotype-phenotype association helps guide clinical diagnosis and treatment. However, the treatment for AIP in China is limited and monolithic, and more attention needs to be paid to the treatment.

Objective To analyze the value of combination of red blood cell distribution width（RDW） to platelet（PLT） ratio（RPR）, lactic acid level and APACHE Ⅱ score in predicting the progression of septic shock. Methods A total of 131 patients with sepsis admitted to Shanxi Provincial People’s Hospital from January 2019 to December 2021 were enrolled,including 62 septic shock cases and 69 non-shock cases. PLT, RDW, lactic acid, RPR, APACHE Ⅱ score and other indexes were compared between the two groups within 24 h after admission. ROC curve was used to analyze the efficiency of RPR,lactic acid, APACHE Ⅱ score and combination of three incicators to predict septic shock in septic patients. Binary logistic regression was used to analyze the independent risk factors of septic shock in sepsis patients. Results Compared with non-shock group, APACHE Ⅱ score, RPR and lactic acid levels were increased in sepsis shock group, while PLT was decreased（all P＜0.05）. ROC curve analysis showed that AUCs of RPR, lactic acid, APACH Ⅱ score and the combination of three indicators for predicting septic shock were 0.664, 0.687, 0.654 and 0.810, respectively（all P＜0.05）. Binary logistic regression analysis showed that RPR＞0.088, lactic acid＞1.550 mmol/L, APACHE Ⅱ score ≥10.0 were risk factors for septic shock in septic patients（all P＜0.05）. Conclusion RPR, lactic acid level and APACHE Ⅱ score can be used as predictors of septic shock in septic patients, while the combination of three indicators can improve the predicting value.

脓毒症是急诊科、重症医学科常见病,中心静脉-动脉二氧化碳分压差与动脉-中心静脉氧含量比值(Pcv-aCO2/Ca-cvO2)可反映机体氧供需状态,以氧供应不足及氧摄取利用受限为特征的氧代谢障碍是脓毒症主要的病理生理机制之一,并成为危重症患者病情发展至多器官功能衰竭的共同基础.本文从Pcv-aCO2/Ca-cvO2评估脓毒症患者氧代谢方面进行总结,以期为脓毒症患者的诊疗提供帮助.

脓毒症相关急性肾损伤(sepsis-associated acute kidney injury,S-AKI)是急诊科和重症监护病房中脓毒症患者最常见的并发症之一,其病死率极高.S-AKI的早期诊断和可靠监测对预防脓毒症患者进展为多器官功能衰竭甚至死亡至关重要.目前虽然对 S-AKI的发病机制、诊断和治疗进行了广泛研究,但仍未找到理想的指标来早期诊断和监测该疾病,这是当前面临的具有重大挑战性的问题.本文对近年来早期预测S-AKI的标志物进行总结,分析新型生物学标志物在S-AKI等危重症患者救治过程中的作用,旨在为临床 S-AKI患者提供帮助.

目的 探讨血小板压积(plateletcrit,PCT)联合收缩压(systolic blood pressure,SBP)和急性生理与慢性健康评分(Acute Physiology and Chronic Health Evaluation,APACHE Ⅱ评分)对脓毒性休克的预测价值.方法 入选2018年1月～2021年12月山西省人民医院收治的131例脓毒症患者作为研究对象,记录患者基线资料和临床数据.根据是否发生脓毒性休克,将131例患者分为脓毒症组(n=68)和脓毒性休克组(n=63).比较两组临床资料,采用二元Logistic回归模型分析发生脓毒性休克的独立危险因素.采用受试者工作特征(receiver operating characteristic,ROC)曲线评价PCT、SBP和APACHE Ⅱ评分及三者联合对脓毒性休克的预测价值.结果 两组患者年龄、性别、C反应蛋白、血小板分布宽度和白细胞计数等比较,差异无统计学意义(P＞0.05).与脓毒症组比较,脓毒性休克组收缩压、舒张压、血小板计数、血小板压积和嗜酸性粒细胞计数显著降低;心率、D二聚体、降钙素原、序贯器官衰竭评估(sequential organ failure assessment,SOFA)评分和APACHE Ⅱ评分升高,差异有统计学意义(P＜0.05).Logistic回归分析显示,低PCT、低SBP和APACHE Ⅱ评分是脓毒症休克的独立危险因素.ROC曲线分析显示,PCT、SBP和APACHE Ⅱ预测脓毒症发生的曲线下面积(area under the curve,AUC)分别为0.653、0.665和0.692,而三者联合后,曲线下面积为0.794.结论 血小板压积可作为预测脓毒性休克的指标,与收缩压及APACHE Ⅱ评分联合能够提高预测脓毒性休克的准确性.

RNA的正确剪接是基因正常表达的关键.近年来,随着第二代高通量测序技术的快速发展以及对变异解读的不断深入,发现相较于错义变异及无义变异,剪接变异的漏检率很高,并且越来越多的证据证实了剪接变异在遗传病发病机制中的重要性.本综述简要概述了剪接的基础,并以几种单基因遗传病为例阐述剪接变异的致病机制,包括常见剪切变异类型及引起的mRNA效应,强调了剪接变异是引起单基因遗传病的重要机制,以期引起大家对剪接变异的关注,提高遗传病的诊断率.

BackgroundChina's research on acute intermittent porphyria (AIP) is relatively limited. Due to most medical workers' insufficient understanding, AIP is easily misdiagnosed, and mistreated, leading to delayed appropriate treatment.ObjectiveTo analyze the clinical data of Chinese individuals with AIP with hydroxymethylbilane synthase (HMBS) gene mutation who were reported in published studies, improving medical workers' understanding of AIP.MethodsDatabases of PubMed, CNKI, Wanfang Data and CQVIP were searched for published articles about Chinese AIP cases from inception to June 30, 2021. Literature screening based on the inclusion and exclusion criteria of this study and data extraction were performed by two researchers, separately. Information regarding general data, clinical manifestations, results of laboratory tests, treatments, and gene mutations of AIP patients was analyzed.ResultsA total of 32 articles were included, containing 65 AIP patients (56 females and 9 males) with the age mostly between 20-39 years old 〔83.1% (54/65) 〕. Most of AIP patients' admission were for abdominal pain〔63 cases (96.9%) 〕, often accompanied by nausea, vomiting, and constipation. 56.9% (37/65) of AIP patients suffered from central neuropathy, disturbance of consciousness (25 cases) , epileptiform seizures (22 cases) and respiratory muscle paralysis (6 cases) . 13.8% (9/65) of patients experienced peripheral neuropathy including fatigue (6 cases) and limb numbness (4 cases) . 30.8% (20/65) of patients had autonomic neuropathy such as hypertension and tachycardia. 9.2% (6/65) of patients experienced spirit symptoms, such as depression, anxiety and hallucination. Thirty-five patients had generated multiple acute attacks of AIP. In some patients, the onset of AIP may have been related to menstruation (9 cases) , pregnancy and childbirth (4 cases) , fatigue (3 cases) , alcohol consumption (2 cases) , and dieting (1 case) . 25 patients developed hyponatremia. There were 11 cases of anemia and 11 cases of abnormal liver function. Six patients were in abnormal renal function. 1 case was caught in disorder of cortisol rhythm. Twenty-seven patients received carbohydrate loading therapy, and 25 of them were improved. Two patients were treated with carbohydrate loading combined with heme therapy, and 1 eventually improved. A total of 26 HMBS gene mutations were included in the study, where in the p.R173W, p.R173Q, p.T269R, p.W283X and p.A330P mutations were detected in multiple patients. And different patients with the same gene mutation may also show different clinical phenotypes.ConclusionAIP is a disease with complex and variable clinical manifestations and heterogeneous severity of disease. The acute attack of AIP should be considered if patients, especially young female patients, are clinically found to be with unexplained abdominal pain, epileptiform seizures, disturbance of consciousness, hypertension, tachycardia and hyponatremiain. Currently, carbohydrate loading therapy is mainly applied to control the attack of AIP in China. In terms of factors affecting the clinical phenotype of AIP, further exploration still needs to be carried out.

低钠血症是临床常见的水盐失衡类型,严重的低钠血症及纠正过快可能对神经系统造成不可逆损伤,老年人群常见低钠血症,脑桥中央髓鞘溶解是罕见且凶险的不良结局之一.现报道1例重度低钠血症伴发脑桥中央髓鞘溶解的老年病人,并进一步总结分析病因,以提高低钠血症诊治的规范.

Acute intermittent porphyria (AIP) is a rare disease caused by enzyme deficiency due to HMBS gene mutation and is often life-threatening during acute attack. This article introduces the traditional treatment methods for AIP, such as high-carbohydrate therapy and intravenous heme infusion, as well as several emerging therapies targeting the etiology of AIP, including enzyme replacement therapy and gene therapy with multiple strategies of DNA gene augmentation, mRNA gene augmentation, and RNAi gene silencing. It is worth noting that breakthroughs have been made in Givosiran, a drug based on RNAi gene silencing, and it has been used in clinical practice. Gene therapy targeting the etiology of AIP may become a new trend in the treatment of rare diseases in the future.

目的 观察隔药温针灸治疗女性盆腔炎性疾病(PID)后遗慢性盆腔痛(CPP)的临床疗效.方法 将符合纳入标准的70例寒湿凝滞型CPP患者按随机数字表法以1:1比例分为试验组和针刺组,每组35例.试验组予隔药温针灸,对照组予常规针刺治疗.观察两组治疗前后和随访时视觉模拟量表(VAS)评分、盆腔痛客观体征(McCormack)评分和中医证候评分的变化,比较两组临床疗效.结果 共67例CPP患者完成本研究.两组治疗前VAS评分、McCormack评分和中医证候评分比较,差异均无统计学意义(P>0.05);两组治疗后和随访时上述各项评分均优于同组治疗前(P<0.05),且试验组治疗后和随访时上述各项评分均优于针刺组(P<0.05).试验组临床总有效率为100.0％,高于针刺组的82.4％,差异有统计学意义(P<0.05).结论 隔药温针灸治疗女性盆腔炎性疾病后遗慢性盆腔痛的临床疗效优于常规针刺.

目的探讨血尿酸和血脂在急性冠脉综合征(ACS)患者中的变化和临床意义。方法筛选70例不稳定型心绞痛(UAP)患者为UAP组,50例急性心肌梗死(AMI)患者为AMI组,42例冠脉造影阴性者(CON)为CON组,进行血尿酸和血脂含量分析。结果血尿酸分别与三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)做Pearsoncor relations分析,血尿酸与HDL呈负相关,与LDL、TC、TG呈正相关。AMI组和UAP组血尿酸、LDL、TC、TG含量显著高于CON组(P<0.05)。结论尿酸浓度升高和血脂升高可能与急性冠脉综合征患者的发病有一定的关系。