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

Basilar artery pseudoaneurysm (BAPA) is an extremely rare yet life-threatening intracranial vascular lesion, characterized by insidious clinical onset and a remarkably high mortality risk upon rupture. In this case report, we describe a patient who was admitted to our department with spontaneous subarachnoid hemorrhage (SAH). Emergency digital subtraction angiography performed on admission revealed no vascular anomalies. One month after SAH onset, a comprehensive multimodal imaging evaluation ultimately confirmed the diagnosis of BAPA. Given the technical challenges in conventional management for this specific case, Traxcess-14 microguidewire-assisted endovascular electrocoagulation was performed as a last-resort therapy. Finally, follow-up imaging at 6 months demonstrated complete resolution of BAPA. Thus, we propose that Traxcess-14 microguidewire-assisted endovascular electrocoagulation may serve as a potential salvage treatment for highly selective BAPA cases in which conventional therapeutic approaches are unfeasible or have failed.

OBJECTIVE To investigate the ameliorative effects of Coptidis Rhizoma-Ophiopogonis Radix herb pair （HLMD） in rats with type 2 diabetes mellitus （T2DM） and its potential mechanisms.METHODS Male Wistar rats were randomly divided into a control group （6 rats） and a model induction group （30 rats）. The T2DM rat model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The successfully modeled rats were subsequently divided into the model group， the metformin group （200 mg/kg）， and the low-， medium-， and high-dose HLMD groups （100， 200 and 400 mg/kg， respectively）， with six rats in each group. Rats in each group were administered the corresponding drug solution or normal saline by oral gavage once daily for six consecutive weeks. Body weight， fasting blood glucose （FBG）， the area under the curve （AUC） of the oral glucose tolerance test， serum lipid profiles [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， and inflammatory cytokine [interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α）， and IL-10] levels were measured. Histopathological changes in liver and pancreatic tissues， as well as hepatic lipid accumulation， were evaluated. Changes in gut microbiota composition were analyzed in the control， model， and high-dose HLMD groups. Network pharmacology and molecular docking analyses were performed to identify potential therapeutic targets of HLMD against T2DM， followed by experimental validation.RESULTS Compared with the model group， the body weight generally recovered in rats in all HLMD dose groups， while FBG levels consistently decreased. Histopathological abnormalities， including disrupted pancreatic islet architecture， disorganized hepatocyte arrangement， hepatic cord necrosis， and lipid accumulation， were alleviated to varying degrees. AUC （except for the low-dose group）， levels of TC， TG， LDL-C， IL-6（except for the low-dose group）， IL-1β and TNF-α， Simpson and Shannon indices， as well as the relative abundances of Firmicutes， Proteobacteria， and Clostridium were significantly reduced； meanwhile， the levels of HDL-C（except for the low-dose group） and IL-10 （except for the low-dose group）， as well as the relative abundances of Bacteroidota and Ligilactobacillus were significantly increased （ P ＜0.05）. Network pharmacology and molecular docking analyses suggested that the active constituents of HLMD， including quercetin， adenosine， oleanolic acid， stigmasterol， and ophiopogonin D′， may exert antidiabetic effects by targeting key proteins such as protein kinase B1（Akt1）， TNF， IL-6， P53 and IL-1β. Experimental validation further demonstrated that HLMD significantly downregulated the protein expressions of P53 （except for the low-dose group）， IL-6 （except for the low-dose group）， IL-1β and TNF-α in the liver tissues of T2DM rats （ P ＜0.05）.CONCLUSIONS HLMD alleviates glucose and lipid metabolism disorders， attenuates inflammatory responses， and ameliorates hepatic and pancreatic tissue damage in T2DM rats. These beneficial effects may be associated with the modulation of gut microbiota composition and the downregulation of inflammation-related targets， including P53， IL-6， IL-1β and TNF-α.

Objective:To assess performance advantages of voxel-less optimization(VoLO)algorithm of CyberKnife-based S7 treatment plan system for the optimization of stereotactic body radiation therapy(SBRT)for liver cancer.Methods:The case data of 20 patients with hepatocellular carcinoma from Chinese PLA General Hospital during June 2022 and April 2023 were retrospectively selected,which included 10 patients with large hepatocellular carcinoma and 10 patients with small hepatocellular carcinoma.All patients adopted respectively sequential optimization(SO)and VoLO to conduct optimization for plan.The optimized quality of plan and execution efficiency of two kinds of algorithms were assessed,and the influences of different tumor volumes also were considered.The planed quality assessment included dosimetric parameters of the target region and organ at risk(OAR).The assessment parameters of execution efficiency included the numbers of monitor units(MUs),nodes and beams,and estimated treatment time.Paired t-test method was adopted to analyze quality of plan and treatment efficiency.Results:On the aspect of the dose of target region,for small hepatocellular carcinoma,the conformity index(CI)value(1.08±0.05)of target region of VoLO algorithm was significantly better than(1.17±0.06)of SO algorithm(t=4.631,P<0.05).The gradient index(GI),coverage rate and dose by 95%(D95%)of VoLO algorithm were better than those of SO algorithm,while the differences were not significant(P>0.05).According to the defined standards of liver surgery,for large hepatocellular carcinoma,the differences in CI,GI,coverage rate and D95%of target region between two kinds of algorithms were significant(t=3.337,4.238,-3.359,-3.311,P<0.05),respectively.On the aspect of dosimetry for OAR,for the target region of large hepatocellular carcinoma,the differences of liver Dmean and D700 cm3 between two kinds of algorithms were significant(t=4.114,3.415,P<0.05).However,for small hepatocellular carcinoma,there was no significant statistical difference in dosimetry parameters of OAR between two kinds of algorithms(P>0.05).The execution efficiency of the plan of VoLO group was obviously higher than that of SO group,and the differences of MU number,node number,beam number and estimated treatment time between two groups were significant(t=12.661,4.423,5.024,9.487,P<0.05).Conclusion:The quality of VoLO plan is significantly better than that of SO,which has a significant improvement in execution efficiency of treatment.For the cases of large hepatocellular carcinoma with more complexity,the VoLO optimization shows better advantages on the aspect of dose on target region,and protection for normal liver.

Objective:To investigate the factors influencing sound localization in patients with unilateral sudden sensorineural hearing loss, so as to provide the reference for hearing rehabilitation of patients with unilateral sudden hearing loss.Methods:This study was a cross-sectional study that retrospectively analyzed the clinical data and audiological examination results of 228 patients with unilateral sudden sensorineural hearing loss(103 males and 125 females; aged from 18 to 80 years, with an average age of 46.2 years; 107 cases in the left ear and 121 cases in the right ear; 8 cases of low-frequency decline type, 42 cases of high-frequency decline type, 92 cases of flat decline type, and 86 cases of total deafness type)at the Eye and ENT Hospital of Fudan University from June 2023 to April 2024. The minimum audible angle (MAA) was calculated by the angle discrimination test of 1000 Hz and 4000 Hz warble tones, which were recorded as MAA 1 000 and MAA 4 000 according to the frequency of the given sound stimulus. The root mean square error (RMSE) was calculated by the angle recognition test with daily natural sounds as the stimulus sound. Using SPSS 27.0 statistical software, correlation and multiple regression analysis were used to research the clinical factors affecting the ability of sound localization in patients with unilateral sudden sensorineural hearing loss. Results:The mean MAA 1 000, MAA 4 000, RMSE of patients with unilateral sudden deafness were (53.97±29.14)°, (46.34±28.87)° and (30.06±13.64)°, respectively. Univariate analysis of variance revealed that there were significant differences between different classifications of sudden sensorineural hearing loss for sound localization tests (MAA 1 000: F=6.338, P<0.001,MAA 4 000: F=14.334, P<0.001,RMSE: F=49.918, P<0.001), post-hoc analysis observed that all significant contrasts were included the type of total deafness and low-frequency deafness. Correlation analysis showed the age of subjects in this study was weak positively correlated to the MAA 1 000 ( r=0.165, P=0.013), the duration of sudden sensorineural hearing loss was weak negatively related to RMSE ( r=-0.144, P=0.030), there were significant positive relationships between the threshold of PTA, PTA 1kHz, PTA 4kHz for the affected side, as well as the binaural PTA difference and sound localization test (MAA 1 000,MAA 4 000,RMSE) (all P<0.001). The multiple regression analysis showed the age and the binaural PTA difference for the affected side were the significant factors for the MAA 1 000 and MAA 4 000, the binaural PTA difference was the significant factors for the RMSE. The R 2 of multivariable linear regression model for MAA 1 000, MAA 4 000 and RMSE results in unilateral sudden deafness patients were 0.149, 0.207 and 0.553, respectively. Conclusion:Age, the hearing of the affected side, and binaural PTA difference are the significant factors for sound localization ability in patients with unilateral sudden sensorineural hearing loss, hearing compensation of the affected ear for these patients is hopeful to enhance the sound localization ability.

Objective:To evaluate the relationship between transverse sinus stenosis (TSS) and cerebral blood flow in normal adults based on four-dimensional flow (4D Flow) MRI.Methods:The study was a cross-sectional study. Totally 81 normal volunteers who underwent magnetic resonance venography (MRV) and 4D Flow MRI were prospectively enrolled at Beijing Friendship Hospital, Capital Medical University from January 2020 to December 2022. Based on MRV evaluation of transverse sinus dysplasia, the volunteers were divided into a dysplasia group (26 cases) and a non-dysplasia group (55 cases); The area of the stenosis and the normal transverse sinus at the distal end were measured. The degree of TSS and the bilateral average transverse sinus stenosis (BA-TSS) were calculated. TSS was determined using TSS levels of 1/3, 1/2, and 2/3 as thresholds, and was divided into three groups: no TSS group, unilateral TSS group, and bilateral TSS group, with 28, 39, and 14 cases, 37, 37, and 7 cases, and 43, 36, and 2 cases, respectively. Based on 4D Flow MRI, the blood flow of the internal carotid artery, vertebral artery, superior sagittal sinus, straight sinus, and transverse sinus distal and proximal ends were measured. The cerebral blood flow (bilateral internal carotid artery blood flow+bilateral vertebral artery blood flow), venous sinus return blood flow 1 (superior sagittal sinus blood flow+straight sinus blood flow), return blood flow 2 (sum of bilateral transverse sinus distal end blood flow), return blood flow 3 (sum of bilateral transverse sinus proximal end blood flow), and the ratio of return blood flow to cerebral blood flow were calculated. Independent sample t-test was used to compare the differences between the group with and without transverse sinus dysplasia; Single factor analysis of variance was used to compare the differences between the TSS free group, unilateral TSS group, and bilateral TSS group. Based on single factor linear regression, the relationships between BA-TSS and blood flow parameters were analyzed.Results:There was no statistically significant difference in various blood flow parameters between the group with and without transverse sinus dysplasia (all P>0.05). When using 1/3, 1/2, and 2/3 as thresholds, there was no statistically significant difference in various blood flow parameters between the non TSS group, unilateral TSS group, and bilateral TSS group (all P>0.05). BA-TSS was linearly positively correlated with cerebral blood flow (β=0.986, 95% CI 0.108-1.865, P=0.028), but not linearly correlated with return blood flow 1, 2, and 3 (all P>0.05). The degree of BA-TSS was linearly negatively correlated with return blood flow 1/cerebral blood flow (β=-0.001, 95% CI -0.002-0, P=0.009) and return blood flow 2/cerebral blood flow (β=-0.001, 95% CI -0.002-0, P=0.018), but not with return blood flow 3/cerebral blood flow ( P=0.076). Conclusion:The BA-TSS degree in normal adults is positively correlated with cerebral blood inflow and negatively correlated with the proportion of venous sinus outflow.

Objective:To evaluate the application effect of improved problem-based learning (PBL) based on 5W2H thinking in the course of "massage therapy".Methods:The undergraduate students in Class 1 and Class 2 of Acupuncture and Massage in the first semester of the 2023-2024 academic year at Heilongjiang University of Chinese Medicine were selected as the research subjects. The "massage therapy" was taught in Class 1 with the traditional method (control group, n=66) and in Class 2 with the method of improved PBL with 5W2H thinking (observation group, n=68). The two groups of students were compared in terms of theoretical knowledge of massage therapy, the assessment of massage skills, comprehensive ability, innovation ability, and practical ability, as well as the procedural evaluation indicators of massage. SPSS 25.0 was used for normality test and t test χ2 test. Results:After the completion of the study, the observation group showed higher scores in theoretical knowledge (90.56±11.73), massage skill proficiency [(87.22±11.57) vs. (78.23±9.45)], massage skill demonstration [(84.56±11.20) vs. (74.69±9.13)], mannequin usage [(82.98±10.75) vs. (72.66±8.89)], and massage skill mechanics [(86.38±11.45) vs. (73.35±8.94)] compared to the control group. The observation group also outperformed the control group in medical humanities [(85.53±10.64) vs. (64.86±7.33)], teacher-student and student-student interaction [(85.35±8.67) vs. (80.15±7.46)], clinical thinking and operation [(90.05±12.13) vs. (74.26±8.94)], and team coordination and cooperation [(85.60±10.06) vs. (81.53±9.33)]. In addition, the observation group scored higher than the control group in learning participation rate [(18.20±3.75) vs. (13.15±2.93)], error correction rate [(27.56±5.85) vs. (22.11±4.62)], operational stability [(48.43±7.79) vs. (42.06±6.60)], and total score [(94.19±7.56) vs. (77.32±6.78)].Conclusions:The application of improved PBL based on 5W2H thinking in the course of "massage therapy" has significant clinical implications. It can not only improve the teaching quality and effect, but also cultivate students' clinical thinking, teamwork, learning interest, and innovation ability, making it suitable for further promotion and application.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Background and Aims:Body mass index(BMI),an important indicator of nutrition and health,is closely associated with postoperative complications.This study was performed to investigate the relationship between preoperative BMI and severe complications in patients undergoing liver resection for hepatolithiasis,aiming to provide preoperative guidance for clinicians,reduce the risk of postoperative complications,and ensure surgical safety and efficacy.Methods:The clinical data of 484 patients with hepatolithiasis who underwent liver resection between May 2006 and December 2022 at the First Affiliated Hospital of Army Medical University and Beijing Tsinghua Changgung Hospital were retrospectively collected.Patients were classified into low BMI group(≤18.4 kg/m2),normal BMI group(18.5-24.9 kg/m2),and high BMI group(≥25.0 kg/m2)based on preoperative BMI.Baseline characteristics,overall complications,severe complications,and other postoperative outcomes were compared between the normal BMI group and the low group as well as the high BMI group.Risk factors for severe complications after liver resection were analyzed.Results:Among the 484 patients,79(16.3％)were in the low BMI group,328(67.8％)in the normal BMI group,and 77(15.9％)in the high BMI group.The high BMI group had significantly higher ASA score,preoperative albumin level,and proportion of hypertension compared to the normal BMI group(all P＜0.05).Baseline characteristics in the low BMI group showed no significant differences compared to the normal BMI group(all P＞0.05).The incidence rates of overall complications were not significantly among the three groups(P＞0.05).However,the high BMI group had significantly higher incidence rates of severe complications(Clavien-Dindo grade Ⅲ-Ⅳ),postoperative infections,liver failure,and bile leakage compared to the normal BMI group;the low BMI group had significantly higher rates of perioperative blood transfusion,postoperative infections,liver failure,and reoperation compared to the normal BMI group(all P＜0.05).Univariate and multivariate Logistic regression analyses identified high BMI and preoperative total bilirubin ≥54 pmol/L as independent risk factors for severe complications after liver resection in patients with hepatolithiasis(both P＜0.05).Conclusion:Preoperative BMI is closely associated with the occurrence of complications after liver resection in patients with hepatolithiasis,with high BMI being an independent risk factor for severe complications.To mitigate the risk of severe complications,clinical practice should prioritize monitoring and management of individuals with high BMI and other risk factors