BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

With the process of China’s aging population intensifying， palliative care， as an important guarantee for improving the quality of life of terminally ill patients， is receiving more and more social attention， and the demand is constantly increasing. Palliative care needs versatile professionals， and general education can enhance people’s awareness and understanding of it， enabling more people to understand， accept， and participate in palliative care. With the advancement of knowledge and technology in palliative care， the traditional cramming education models are no longer able to meet the actual needs. Therefore， there is an urgent need to innovate palliative care education strategies. By analyzing the current problems in the general education of palliative care in China， this paper proposed thoughts and suggestions for general and innovative education of palliative care in several aspects， such as establishing general and innovative education systems and evaluation systems of palliative care， diversifying educational contents and methods， strengthening medical staffs training， promoting diversified student groups， and strengthening the popularization of palliative care knowledge among the public.

Renal cell carcinoma is one of the significant diseases endangering human health. Recent findings have shown that the human microbiome plays an important role in the occurrence and development of renal cell carcinoma, influencing its regression and treatment outcome. At present, microecological research on renal cell carcinoma are still in their initial stages, and their regulatory roles and specific mechanisms still need to be further explored. This article reviews the relationship between the human microbiome and renal cell carcinoma occurrence and development, as well as its role in diagnosis and therapies.

Stroke has the highest morbidity and mortality in the adults of China, with heavy burden to the society and family. In recent years, the third generation of thrombolytic drug tenecteplase has made breakthrough in many fields of acute ischemic stroke reperfusion, and has been recommended by domestic and foreign guidelines for intravenous thrombolysis or intravenous thrombolysis bridging to mechanical thrombectomy for acute ischemic stroke. Results of several large clinical trials of tenecteplase have been published in the European Stroke Organization Conference in 2024, which provides more evidence-based medical evidences for tenecteplase in acute ischemic stroke reperfusion. This article reviews the latest research on tenecteplase in acute ischemic stroke reperfusion, and looks forward to the future direction of this field, in order to provide some references for clinicians and further related clinical study using tenecteplase.

OBJECTIVE: To analyze the clinical features of overweight and obese rheumatoid arthritis (RA)patients, and the relationship between body mass index (BMI) and disease characteristics. METHODS: The demographic data, extra-articular manifestations, comorbidities, and disease activity of RA patients admitted to the Rheumatology and Immunology Department of Peking University Third Hospital from January 2015 to December 2020 were collected, and the above characteristics of overweight and obese RA patients were retrospectively analyzed. According to the WHO, BMI≥30 kg/m² referred to obese individuals, 25≤BMI < 30 kg/m² referred to overweight individuals, 18.5≤BMI < 25 kg/m² referred to normal individuals, BMI < 18.5 kg/m² referred to reduced body mass individuals. t test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non-normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, Chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. Analyzing whether overweight or obesity was associated with comorbidities using Logistic regression adjusted confounding factors. RESULTS: A total of 481 RA patients were included in this study, with an average BMI value of (23.28±3.75) kg/m².Of the patients, 31 cases (6.5%) were with BMI < 18.5 kg/m², 309 cases (64.2%) with 18.5≤ BMI < 25 kg/m², amounting to 340 cases (70.7%). There were 119 overweight individuals (25≤ BMI < 30 kg/m², 24.7%) and 22 obese individuals (BMI≥30 kg/m², 4.6%), totaling 141 (29.3%).The proportion of the overweight and obese RA patients suffering from hypertension (57.4% vs. 39.1%, P < 0.001), diabetes (25.5% vs. 15.0%, P=0.006), hyperlipidemia (22.7% vs. 10.9%, P=0.001), fatty liver (28.4% vs. 7.4%, P < 0.001), osteoarthritis (39.0% vs. 29.4%, P=0.040) was significantly higher, and the proportion of the patients with osteoporosis(59.6% vs. 70.9%, P=0.016) and anemia (36.2% vs. 55.6%, P < 0.001) was significantly lower. However, there was no difference between the two groups in coronary heart disease (5.7% vs. 7.6%, P=0.442), cerebrovascular disease (6.4% vs. 8.8%, P=0.372) and peripheral atherosclerosis (9.2% vs. 7.6%, P=0.565).The median C-reactive protein (CRP, 1.52 mg/dL vs. 2.35 mg/dL, P=0.008), median erythrocyte sedimentation rate (ESR, 34.0 mm/h vs. 50.0 mm/h, P=0.003), pain visual simulation score (VAS) (3.66±3.08 vs. 4.40±2.85, P=0.011), and 28 joint disease activity scores (DAS-28, 5.05±1.60 vs. 5.45±1.52, P=0.010) in the overweight and obese RA group were all lower than those in the normal and reduced weight groups. Multivariate regression analysis showed that overweight and obesity was an independent risk factor for hypertension, diabetes, hyperlipidemia and fatty liver, and had protective effects on osteoporosis and anemia. CONCLUSION In RA patients, RA disease activity is lower in overweight and obesity patients. Overweight and obesity is associated with hypertension, diabetes and hyperlipidemia, but not with cardiovascular and cerebrovascular diseases.
Humans ; Body Mass Index ; Overweight/epidemiology* ; Retrospective Studies ; Arthritis, Rheumatoid/epidemiology* ; Obesity/epidemiology* ; Diabetes Mellitus ; Hypertension/complications* ; Fatty Liver/complications* ; Hyperlipidemias/complications* ; Osteoporosis/complications* ; Anemia

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype