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

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

ObjectiveObesity, a global chronic metabolic disease, is closely associated with disruptions in lipid metabolism and gut microbiota. Current intervention strategies still have limitations in terms of safety and microecological regulation, necessitating the exploration of novel natural regulatory approaches. Based on the early pathological characteristics of obesity, this study innovatively employs a rectal delivery method alongside a high-fat diet (HFD)-induced obesity model to systematically evaluate the inhibitory effects, safety, and gut microbiota regulation mechanisms of leek-derived and konjac-derived extracellular vesicles on obesity development. By simulating early clinical intervention scenarios, this study aims to explore the preventive potential of plant-derived extracellular vesicles during the initial stages of obesity onset. MethodsExtracellular vesicles from leek and konjac were isolated using ultracentrifugation combined with density gradient centrifugation. Their nanoscale properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). Male C57BL/6J mice were randomly divided into four groups: normal control (NC), high-fat diet (HFD), leek-derived extracellular vesicles (LEVs), and konjac-derived extracellular vesicles (KEVs). Beginning simultaneously with HFD feeding, mice in the intervention groups received 20 g/L vesicles rectally every 3 d for 4 weeks. Body mass and body composition were monitored throughout. At endpoint, mouse serum, adipose tissue, and colonic contents were collected. Serum biochemical indices (lipid profile, liver and kidney function, cardiac markers) were assessed to evaluate safety and metabolic efficacy, while 16S rRNA sequencing was employed to analyze gut microbial structure and diversity. ResultsDLS, NTA, and TEM confirmed that both LEVs and KEVs exhibited typical cup-shaped nanostructures with average particle sizes of approximately 284 nm and 223 nm, respectively. LEVs and KEVs treatment significantly suppressed HFD-induced weight gain and elevation of body-fat percentage (P<0.05), and reduced accumulation of abdominal white and epididymal adipose tissue. Serological analyses showed that both vesicles lowered total cholesterol, triglycerides and LDL-cholesterol, and ameliorated liver enzyme profiles (ALT, AST), demonstrating lipid-metabolic regulation and hepatoprotective effects. No hepatic, renal or cardiac dysfunction was observed, indicating favorable safety. Gut microbiota analyses revealed that vesicle intervention partially restored HFD-depleted microbial diversity and reshaped community structure. Notably, LEVs markedly increased the relative abundance of the beneficial taxon Lachnospiraceae at the family level, which is known for producing short-chain fatty acids and enhancing intestinal barrier function. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional prediction suggested that LEVs and KEVs modulated gut microbial functions through distinct mechanisms: LEVs downregulated pathways related to ribosomes and DNA replication while enhancing xenobiotic degradation, whereas KEVs tended to upregulate energy metabolism and protein synthesis toward healthy levels. ConclusionRectally administered LEVs and KEVs exhibit excellent safety and pronounced metabolic benefits during the early phase of obesity, suppressing weight gain, correcting lipid dysregulation, and exerting effects via modulation of gut microbial composition and function. This study provides systematic experimental evidence supporting plant-derived exosome-like vesicles as an early intervention strategy against obesity.

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）.

Objective To analyze the application of NCompass nitinol stone retrieval basket in ureteroscopic holmium laser lithotripsy, and to evaluate its roles in reducing stone retropulsion and improving stone-free rate(SFR)and stone acquisition rate.Methods A retrospective analysis was conducted on the data of patients with upper ureteral stones＞1 cm who underwent ureteroscopic holmium laser lithotripsy at China-Japan Friendship Hospital during Jan.2018 and Dec.2023, including 96 cases were in the NCompass group, and 68 cases in the non-basket group.The operation time, stone retropulsion rate, usage rate of flexible ureteroscopy, SFR and stone acquisition rate were compared between the two groups.Results There were no significant differences in the operation time [(29.2±8.4)min vs.(30.9±7.2)min, P=0.170] and stone retropulsion rate(15.6% vs. 27.9%, P=0.055)between the NCompass group and non-basket group.The NCompass group had significantly lower usage rate of flexible ureteroscopy than the non-basket group(24.0% vs. 47.1%, P=0.002), higher SFR 2 days(80.2% vs. 45.6%, P＜0.001)and 1 month(93.8% vs. 83.8%, P=0.040)after operation, as well as the stone acquisition rates 2 days(100% vs. 44.1%, P＜0.001)and 1 month(100% vs. 58.8%, P＜0.001)after operation. Conclusion The NCompass nitinol stone retrieval basket plays dual roles in ureteroscopic holmium laser lithotripsy, which can effectively intercept stones and extract stone fragments, thus significantly improving the SFR and stone acquisition rate, and reducing stone retropulsion and the use of flexible ureteroscopy.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

OBJECTIVES: Urinary calculi are characterized by a high recurrence rate, and patients' adherence to self-management after discharge directly affects health outcomes. Traditional offline follow-up models often face problems such as poor compliance and uneven allocation of medical resources, making it difficult to meet individualized health management needs. Remote follow-up provides a novel solution to optimize long-term management, improve health literacy, and enhance clinical outcomes. This study aims to evaluate the effect of remote follow-up under an intelligent medical collaborative model on quality of life and health-promoting lifestyle in patients with urinary calculi, and to assess its short-term impact on clinical outcomes. METHODS: A total of 118 patients with urinary calculi admitted to a tertiary hospital in Hunan Province between August and November 2024 were recruited and randomly assigned to a control group (n=59) or an intervention group (n=59). The control group received routine departmental follow-up, while the intervention group underwent remote follow-up based on an intelligent medical collaborative model for one month. Assessments were conducted before discharge (T0), 15 days after discharge (T1), and one month after discharge (T2), using the Wisconsin Stone Quality of Life Questionnaire and the Health-Promoting Lifestyle Profile. At T2, the incidence of forgotten ureteral stents (FUS), ureteral stent-related complications, unplanned readmissions, and patient satisfaction were evaluated. RESULTS: No significant differences were observed between groups at T0 in baseline characteristics or outcome measures (all P>0.05). At T1 and T2, the intervention group had significantly higher health-related quality of life scores than the control group (P<0.05). Generalized estimating equation (GEE) analysis showed significant between-group effects (Wald's χ²=22.961, P<0.001), time effects (Wald's χ²=23.065, P<0.001), and interaction effects (Wald's χ²=6.930, P<0.05). Similarly, at T1 and T2, the intervention group scored significantly higher on health-promoting lifestyle than the control group (P<0.05), with significant between-group effects (Wald's χ²=22.936, P<0.001), time effects (Wald's χ²=10.694, P<0.001), and interaction effects (Wald's χ²=18.921, P<0.05). No significant differences were found between groups in the incidence of FUS, ureteral stent-related complications, or unplanned readmissions (all P>0.05). Patient satisfaction was significantly higher in the intervention group (t=4.089, P<0.001). CONCLUSIONS Remote follow-up under an intelligent medical collaborative model helps improve quality of life, promote health-oriented lifestyles, and enhance patient satisfaction among individuals with urinary calculi.
Humans ; Quality of Life ; Male ; Female ; Urinary Calculi/therapy* ; Health Promotion/methods* ; Middle Aged ; Adult ; Follow-Up Studies ; Treatment Outcome

Objective:To evaluate the feasibility and clinical efficacy of transoral endoscopic-assisted submandibular gland resection with low-temperature plasma knife technology, aiming to establish a scarless surgical approach to meet the patients aesthetic demands. Methods:A retrospective analysis was conducted on 5 consecutive patients with benign submandibular gland pathologies treated by a single surgical team between January 2021 and December 2023. All procedures employed a transoral mucosal incision in the floor of mouth, with 0-degree high-definition endoscope assistance and low-temperature plasma knife for precise dissection and hemostasis. Close postoperative follow-up was performed. A systematic literature review compared surgical approaches regarding critical anatomical landmarks, complication profiles, and scar formation. The clinical efficacy of this technique was summarized and analyzed. Results:Successful transoral endoscopic plasma knife resections were performed for benign submandibular conditions（including neoplasms, chronic sialadenitis, and sialolithiasis）. All operations were completed without conversion to open approach. No permanent lingual nerve or marginal mandibular nerve injuries occurred. Transient lingual hypoesthesia recovered within 2 weeks. During 6-12 months follow-up, there was no recurrence and absence of visible cervical scarring, with 100% patient satisfaction regarding cosmesis. Conclusion:Transoral endoscopic plasma knife resection of the submandibular gland demonstrates procedural safety and technical feasibility. This approach offers significant advantages in minimally invasive access, superior aesthetic outcomes, and accelerated recovery, representing a viable novel alternative for benign submandibular gland disease management.
Humans ; Submandibular Gland/surgery* ; Retrospective Studies ; Endoscopy/methods* ; Female ; Middle Aged ; Male ; Treatment Outcome ; Adult

Objective:To investigate the clinical effect of free anterolateral thigh myocutaneous flap combined with oral repair membrane in the reconstruction of nasal mucosa defect after maxillary malignant tumor surgery. Methods:A total of 12 patients with maxillary gingival squamous cell carcinoma and maxillary sinus cancer who had been treated in Department of Oral and Maxillofacial Surgery, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, were selected from November 2020 to November 2023. Free anterolateral thigh musculocutaneous flap transplantation combined with oral repair membrane were used in all patients. Meanwhile, maxillary soft and hard tissue defects and nasal mucosa defects left after tumor operation were repaired and reconstructed. The clinical effect was evaluated after 6-12 months follow-up. Results:Subtotal maxillary resection was performed in 1 case, total maxillary resection in 9 cases and extended maxillary resection in 2 cases. The musculocutaneous flaps of all patients survived, the facial appearance was basically symmetrical, no obvious depression deformity, the swallowing and speech function recovered well, the mouth and nasal cavity were closed completely, the food could be eaten through the mouth, and the lower nasal passage was not blocked. Conclusion:The free anterolateral thigh musculoflap combined with oral repair membrane can be used to repair and reconstruct maxillary malignant tumor complicated with extensive maxillary tissue and nasal mucosa defect after operation, and the appearance and function can be recovered well after operation, which is a choice for maxillary malignant tumor complicated with nasal mucosa defect.
Humans ; Myocutaneous Flap ; Plastic Surgery Procedures/methods* ; Maxillary Neoplasms/surgery* ; Carcinoma, Squamous Cell/surgery* ; Male ; Middle Aged ; Female ; Nasal Mucosa/surgery* ; Maxilla/surgery* ; Thigh/surgery* ; Maxillary Sinus Neoplasms/surgery*