OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg^-1）， medium-dose group （4.86 g·kg^-1）， high-dose group （9.72 g·kg^-1）， and benazepril group （0.01 g·kg^-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveTo investigate the clinical effects and safety of Shuhe Granules （舒和颗粒） in patients with rheumatoid arthritis （RA） comorbid with insomnia. MethodsA single-arm prospective exploratory design was adopted. Thirty RA patients comorbid with insomnia and diagnosed with the traditional Chinese medicine （TCM） syndrome of kidney-heart deficiency and qi-blood disharmony were enrolled. On the basis of maintaining their original RA treatment regimens， all patients received oral Shuhe Granules， one dose per day， for 12 consecutive weeks. The outcomes were assessed before treatment and at weeks 4， 8， and 12 after treatment. Sleep and related psychosomatic function were evaluated using the insomnia severity index （ISI）， Pittsburgh sleep quality index （PSQI）， fatigue severity scale （FSS）， patient health questionnaire-9 （PHQ-9）， generalized anxiety disorder-7 （GAD-7）， and Montreal cognitive assessment （MoCA） scores. RA-related assessments included the 28-joint disease activity score based on C-reactive protein （DAS28-CRP）， pain visual analog scale （VAS）， tender joint count （TJC28）， swollen joint count （SJC28）， morning stiffness duration， and health assessment questionnaire （HAQ） score. Laboratory parameters included erythrocyte sedimentation rate （ESR）， serum C-reactive protein （CRP）， anti-cyclic citrullinated peptide antibody （anti-CCP）， and rheumatoid factor （RF） levels. A literature-based historical control group was established through literature retrieval and meta-analysis. The ISI， PSQI， DAS28-CRP， and pain VAS scores were compared between the treatment group in the present study and the historical control group. Safety assessments were also performed. ResultsCompared with baseline before treatment， ISI and PSQI scores decreased at weeks 4， 8， and 12， while MoCA scores increased at weeks 4， 8， and 12. FSS scores decreased at weeks 4 and 12. At weeks 8 and 12， GAD-7 scores， DAS28-CRP scores， duration of morning stiffness， TJC28， and SJC28 were reduced. At week 12， PHQ-9， pain VAS， and HAQ scores significantly decreased （P＜0.05）. FSS and DAS28-CRP scores at week 12 were lower than those at week 4， and CRP levels at week 8 were lower than those at week 4 （P＜0.05）. Compared with the historical control group， the treatment group showed superior improvement in ISI and PSQI scores （P＜0.001）； however， no statistically significant differences were observed between the two groups in DAS28-CRP or pain VAS scores （P＞0.05）. No serious adverse events occurred during the study， and the 4 reported mild adverse events were all considered unrelated to the study medication. ConclusionShuhe Granules significantly improve sleep quality， fatigue， emotional status， cognitive function， RA-related symptoms， and joint function in patients with RA comorbid insomnia， with good safety and tolerability.

Bronchial asthma （asthma） is a heterogeneous disease characterized by airflow limitation， airway remodeling， and recurrent symptoms such as wheezing， shortness of breath， chest tightness， and cough. Its prevalence is gradually increasing， and a portion of patients are still poorly controlled， leading to a serious social and medical burden. Modern studies have proposed the concept of the "lung-gut axis"， which is based on the crosstalk between microorganisms and their metabolites in the lungs and large intestine， and have indicated that microbial dysbiosis in these organs may affect the onset and progression of asthma. Traditional Chinese medicine （TCM） has found the phenomenon of lung-intestinal comorbidity and put forward the importance of "lung-intestinal coordination therapy" in the treatment of lung-related diseases. It has been found that intestinal flora and their metabolites can modulate immune responses through the lung-gut axis， demonstrating great potential for predicting asthma susceptibility， anticipating phenotypes， assessing asthma severity， and guiding treatment. TCM comopunds that embody lung-intestinal coordination therapy， including herbal formulas， single herbs， acupuncture， moxibustion， acupoint application， and spinal pinching therapy， has been shown to regulate intestinal flora， improve metabolism， regulate immunity， alleviate lung inflammation， reduce mucus secretion， inhibit airway remodeling， effectively alleviate symptoms， and delay lung function decline. Based on "lung-intestinal coordination therapy"， this paper used intestinal flora as the entry point to summarize the underlying mechanisms of TCM in asthma treatment and highlighted the pivotal role of intestinal flora in asthma， providing a new idea for its clinical treatment through the intestinal flora .

Dyskinesia-hyperpyrexia syndrome（DHS）is an acute hyperpyrexia syndrome that is different from Parkinsonism-hyperpyrexia syndrome and serotonin syndrome in patients with advanced Parkinson's disease（PD），with the main symptoms of high fever，disturbance of consciousness，elevated creatine kinase，and dyskinesia. Syndrome of inappropriate secretion of antidiuretic hormone（SIADH）is a clinical syndrome caused by excessive secretion of antidiuretic hormone，which leads to the symptoms of dilutional hyponatremia，water retention，and increases in urine sodium and urine osmotic pressure. DHS has not received widespread attention in clinical practice，and there are rare reports of DHS comorbid with SIADH. This article reports the diagnosis and treatment processes of a case of DHS comorbid with SIADH and reviews the relevant literature，in order to guide the diagnosis and treatment of PD-related critical diseases.
Hyponatremia

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

OBJECTIVE: To evaluate the efficacy and safety of a hospital-made resuscitation pack, a Chinese medicinal herbal compound formula designed to enhance recovery in post-bronchoscopy patients. METHODS: In this randomized, single-blind, placebo-controlled clinical trial, eligible patients were randomly assigned 1:1 to either the treatment or control groups. The patients in the treatment group applied the resuscitation pack, which contained aromatic compounded Chinese herbs. The patients in the control group applied a hospital-made, single herb placebo pack. Packs were placed on the Tiantu (CV 22) acupuncture point for 4 h as soon as the bronchoscopy finished. Efficacy indicators, such as recovery time, patients' symptoms including nausea and dizziness, and adverse events (AEs) were observed and compared. The outcome indices were evaluated at baseline, 1 and 24 h after the bronchoscopy. Subgroup analysis was further performed by patients' age and depth of sedation. RESULTS: When applying generalized estimating equations (GEE) to evaluate the intensity of post-bronchoscopy nausea and vomiting, the intensity was lower in the treatment group (163 cases) compared with the control group (162 cases; 95% CI: 0.004, 0.099, P=0.03]. Also, significantly lower intensity of nausea was observed in the 60-70 years of age subgroup (95% CI: 0.029, 0.169, P=0.006) and deep sedation subgroup (95% CI: 0.002, 0.124; P=0.04). There was no significant difference in dizziness between two groups by GEE (95% CI: -0.134, 0.297; P=0.459). In addition, no serious AEs were observed in either group. CONCLUSIONS Our study found that the resuscitation pack markedly improved patients' symptoms by reducing nausea and vomiting after bronchoscopy without AEs, compared with placebo in the perioperative period. (Trial registration No. ChiCTR2000038299).
Humans ; Male ; Middle Aged ; Female ; Bronchoscopy/adverse effects* ; Single-Blind Method ; Aged ; Drugs, Chinese Herbal/adverse effects* ; Treatment Outcome ; Resuscitation ; Adult ; Medicine, Chinese Traditional

OBJECTIVES: The prevalence of overweight and obesity among children and adolescents continues to rise, becoming one of the most serious global public health issues of the 21st century. Given the differing growth and development environments between urban and rural children, associated risk factors also vary. This study aims to explore the distribution characteristics and influencing factors of overweight and obesity among urban and rural primary and secondary school students in Hunan Province, providing scientific evidence for targeted interventions. METHODS: A stratified, randomized cluster sampling method was used to select participants. A total of 197 084 students from primary and secondary schools across 14 prefectures in Hunan Province underwent physical examinations and questionnaire surveys. Population and spatial distribution characteristics of overweight and obesity were analyzed. Spatial distribution maps and spatial autocorrelation analyses were conducted using ArcGIS. Multivariate Logistic regression was used to identify influencing factors for overweight and obesity. RESULTS: The overall overweight and obesity rates among students in Hunan Province were 14.7% and 10.9%, respectively. Both rates were higher in urban areas than in rural counties (16.0% vs 13.9% for overweight; 12.1% vs 10.2% for obesity). Among both urban and rural students, boys had higher rates of overweight and obesity than girls. Higher-grade students had a higher overweight rate but a lower obesity rate than lower-grade students. In urban areas, the overweight and obesity rates of Han Chinese primary and secondary school students are lower than those of ethnic minority students (both P<0.05). In rural areas, the obesity rate of Han primary and secondary school students is lower than that of ethnic students (P<0.05). Across cities and prefectures, urban overweight and obesity rates ranged from 14.7% to 18.7% and 8.4% to 20.6% respectively, while rural rates ranged from 10.9% to 17.2% and 6.6% to 13.7% respectively. Spatial autocorrelation analysis revealed high-value clusters of overweight/obesity in urban areas of Changde and Zhangjiajie, and in rural areas of Loudi, Huaihua, and Shaoyang. Multivariate Logistic regression showed that gender, school stage, ethnicity, frequency of fresh vegetable intake, and sleep duration were associated with overweight and/or obesity in both urban and rural students. In urban students, frequency of fried food and fresh fruit intake, breakfast habits, physical activity on weekdays and holidays, and screen time on computers were also significant. In rural students, TV viewing time and sedentary duration were additional relevant factors. CONCLUSIONS The situation of overweight and obesity among primary and secondary school students in Hunan Province remains concerning. Greater attention should be paid to regions with high-value clusters of overweight/obesity, and targeted interventions should be developed based on urban-rural differences in influencing factors.
Humans ; China/epidemiology* ; Adolescent ; Male ; Female ; Rural Population/statistics & numerical data* ; Child ; Overweight/epidemiology* ; Students/statistics & numerical data* ; Urban Population/statistics & numerical data* ; Risk Factors ; Prevalence ; Obesity/epidemiology* ; Surveys and Questionnaires ; Pediatric Obesity/epidemiology* ; Schools