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

Objective: To investigate the prevalence of undernutrition and its associated factors among left behind and non left behind primary and secondary school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) areas of central and western China, so as to provide evidence for improving the nutritional status of children and adolescents. Methods: A survey was conducted among 123 782 students selected by random cluster sampling method in grades 3-9 from NIPRCES in central (Hebei, Shanxi, Heilongjiang, Jilin, Anhui, Jiangxi, Henan, Hunan, Hubei, and Hainan) and western (Gansu, Guangxi, Inner Mongolia, Ningxia, Tibet, Shaanxi, Guizhou, Sichuan, Xinjiang, the Xinjiang Production and Construction Corps, Yunnan, Qinghai, and Chongqing) China in 2023. Anthropometric measurements and questionnaires were used to assess nutritional and dietary status. The prevalence of undernutrition was compared between left behind and non left behind students by Chi square test, and associated factors were analyzed by three level Logistic mixed effects model. Results: The prevalence of undernutrition was 8.5% (4 326) in left behind students and 8.1% (5 905) in non left behind students. Three level Logistic mixed effect model analysis showed that whether left behind or non left behind, the undernutrition rates of primary and secondary students in western regions were higher than those of students in central regions [ OR (95% CI )=1.72(1.57-1.87),2.25(2.07- 2.43 )]; the undernutrition risk was lower for those whose fathers had a cultural level of high school or above [ OR (95% CI )=0.69(0.62-0.77),0.90(0.82-0.98)] or junior high school [ OR (95% CI )=0.72(0.66-0.79),0.92(0.85-0.99)] compared to those with primary school or below; picky eating or selective eating increased the risk of undernutrition [ OR (95% CI )=2.36(2.07-2.68),2.28(2.04-2.55)], and primary and secondary school students without nutritional content in health education classes had higher rates of undernutrition [ OR (95% CI )=1.12(1.03-1.23),1.09(1.01-1.17)](all P <0.05). Conclusion The prevalence of undernutrition is slightly higher in left behind primary and secondary students than in non left behind primary and secondary students in central and western NIPRCES areas, with variations across different characteristics.

Objective: To analyze the trends of the frequency of meat, egg, and milk consumption among rural primary and junior high school students in central and western China covered by the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) from 2015 to 2023, so as to provide basis for formulating more targeted nutrition intervention policies and health education strategies. Methods: Using data from six rounds of monitoring and evaluation (2015-2021 and 2023), the study included 323 870 students from grade 3 to 9 across 22 provinces (autonomous regions and municipalities) in central and western China. The consumption frequencies of meat, egg, and milk over the past week were collected via questionnaires. The Cochran-Armitage trend test was used to analyze temporal trends, and multivariable Logistic regression models were employed to analyze factors associated with the frequency of meat, egg and milk consumption and to test for interaction effects between the year and gender, region, and grade level. Results: From 2015 to 2023, the proportion of students consuming meat, egg, and milk ≥1 time/day increased from 23.20 %, 10.71%, and 0.74% to 35.53%, 22.09%, and 26.63%, respectively. Trend tests indicated a significant upward trend for the daily intake of all three food categories for meat, egg and milk over the years ( Z =67.18, 64.90, 93.14, all P <0.01). Multivariable Logistic regression analysis showed that the daily meat intake was lower in the central region than in the western region ( OR=0.77, 95%CI =0.76-0.78), whereas the daily intake of eggs ( OR=1.19, 95%CI =1.17-1.22) and milk ( OR= 1.27 , 95%CI =1.24-1.29) was higher in the central region (all P <0.05). Compared with grade 3-4 students, junior high school students had lower daily intake of meat, eggs, and milk≥1 time/day ( OR =0.95, 0.77, 0.77, all P <0.05), with a declining trend as grade increased. Girls also had lower daily intake of meat, eggs, and milk ≥1 time/day than boys ( OR =0.95，0.93，0.91, all P < 0.05). Significant interactions were observed between year and region, as well as between year and grade (all P <0.05). Conclusion From 2015 to 2023, the NIPRCES improved the intake level of among rural students, but the situation of relatively insufficient intake of egg and milk among females, junior high school students and those in the western region still exists.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Objective: To investigate the impact of milk and egg supplementation on body composition and bone mineral density of rural primary school students in Yunnan Province, so as to provide a reference for developing targeted nutritional intervention strategies. Methods: In December 2023, a cluster sampling method was adopted to select students from grades one to three in four primary schools each from Jinggu and Shidian countys of Yunnan Province, as the intervention group (662 students). Additionally, two boarding primary schools were selected from each county based on the principle of matching scale and student numbers as the control group (455 students). Starting from April 2023, the intervention group received 200 mL milk and 50 g eggs during the break on school days for 8 months, while the control group maintained their usual diet behavior. Body composition was measured by using bioelectrical impedance analysis, and distal radial bone mineral density was assessed via dual energy X-ray absorptiometry in April and December 2023. The intervention effects were analyzed by using a difference in-differences approach. Results: The final measurements of body fat percentage, skeletal muscle mass and fat free mass of the intervention group and the control group of primary school students were significantly higher than the baseline values, and the net effect of milk and egg intervention on these body composition indicators was not statistically significant ( P >0.05, both before and after adjustment). In contrast, bone mineral density increased significantly by 0.02 g/cm 2 in the intervention group. The net intervention effect on bone mineral density was statistically significant ( β=0.02, 95%CI =0.00-0.04), and remained significant after model adjustment ( β=0.02, 95%CI =0.00-0.04) (both P < 0.05). Subgroup analysis showed statistically significant effects of the intervention among girls ( β=0.02, 95%CI =0.00-0.04), day students ( β=0.04, 95%CI =0.01-0.07), and students with normal nutritional status ( β=0.02, 95%CI =0.00-0.04) (all P <0.05). No significant effect of milk and egg supplementation was observed on body composition indicators (all P <0.05). Conclusions Milk and egg supplementation can improve bone mineral density among rural primary school students in Yunnan Province. It is recommended that rural school aged children should increase intake of milk and eggs to support growth and development.

OBJECTIVE: To observe the clinical effect of Tiaoshen Guben holistic therapy of acupuncture and moxibustion (holistic treatment with acupuncture and moxibustion by adjusting the mind and consolidating the root) on comorbidity of depression and insomnia. METHODS: Twenty-four patients with comorbidity of depression and insomnia were included and treated with Tiaoshen Guben holistic therapy of acupuncture and moxibustion. Acupuncture was applied to Baihui (GV20), Guanyuan (CV4), bilateral Neiguan (PC6), etc. The refined moxibustion therapy was delivered at Zhongwan (CV12), Qihai (CV6), bilateral Yongquan (KI1), etc. Subcutaneous embedding therapy with thumb-tack needle was adopted at bilateral Xinshu (BL15), bilateral Pishu (BL20), etc. The intervention was operated once every other day, 3 treatments a week, and for 6 consecutive weeks. Before and after treatment completion, and in 1 month after treatment, Pittsburgh sleep quality index (PSQI) and Hamilton's depression scale (HAMD-17) were adopted to assess sleep quality and depression symptoms in the patients, respectively. Before and after treatment completion, using functional magnetic resonance imaging (fMRI), the functional connectivity (FC) of locus coeruleus (LC) in brain regions was evaluated; and the levels of serum norepinephrine (NE), cortisol (CORT), adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) were detected. RESULTS: Compared with the scores before treatment, PSQI and HAMD-17 scores after treatment completion and in 1 month after treatment were reduced (P<0.01); and strengthened FC was revealed between the right LC and the pars opercularis of the left inferior frontal gyrus, as well as the lateral occipital lobe region. After treatment completion, serum NE was elevated (P<0.01), the levels of CORT, ACTH and CRH were reduced (P<0.01). Before and after treatment completion, the difference in FC between the right LC and the pars opercularis of the left inferior frontal gyrus was negatively correlated with the differences in PSQI score (r = -0.484, P = 0.016) and HAMD-17 score (r = -0.233, P = 0.027). CONCLUSION Tiaoshen Guben holistic therapy of acupuncture and moxibustion can effectively alleviate depression symptoms and improve sleep quality in the patients with comorbidity of depression and insomnia, which is obtained probably through reducing the levels of serum CORT, ACTH and CRH, increasing serum NE, strengthening the FC of the right LC with the pars opercularis of the left inferior frontal gyrus and the lateral occipital lobe region.
Humans ; Moxibustion ; Sleep Initiation and Maintenance Disorders/therapy* ; Male ; Female ; Middle Aged ; Adult ; Acupuncture Therapy ; Depression/complications* ; Aged ; Young Adult ; Acupuncture Points ; Comorbidity

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Background and Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce. Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66). Results: No significant intergroup differences were observed in demographic characteristics except age. The presence of multiple CAF origins (54.3% vs. 4.5%, p<0.001) and multiple draining sites (51.4% vs. 3.0%, p<0.001) were more common in the coils group. In contrast, the presence of aneurysm (72.7% vs. 14.3%, p<0.001), and large fistula (75.8% vs. 37.1%, p<0.001) were more prevalent in the PDA occluders group. The acute procedural success rate of the PDA occluders group was higher compared to that of the coils group (87.9% vs.62.9%, adjusted odds ratio [OR], 7.20; 95% confidence interval, 1.59–32.64; p=0.01).In addition, no significant intergroup differences were noted in both the recanalization rate (7.8% vs. 20%, p=0.107) and the reintervention rate (3.1% vs. 8.6%, p=0.342). Conclusions Transcatheter closure of CAFs using PDA occluders was associated with significantly higher acute procedural success rates compared to coil embolization with comparable late outcomes.