OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with Ehlers-Danlos syndrome, spondylodysplastic type 2 (EDSSPD2). METHODS: A child who was admitted to the Children's Medical Center of the Affiliated Hospital of Guangdong Medical University in July 2024 for "delayed motor development for 1 and a half year" was selected as the study subject. Clinical data of the child was collected, including medical history, family history, and results of auxiliary examinations. Peripheral venous blood samples were collected from the child and his two brothers and both parents. Genomic DNA was extracted from the child and his family members and subjected to whole-exome sequencing (WES) and copy number variation (CNV) analysis. Sanger sequencing was used to verify the parental origin of the candidate variants. Multiple protein function prediction software tools, including SIFT, PolyPhen-2, and REVEL, were used to assess the impact of candidate variants on the protein function. Based on protein database information from UniProt, a two dimensional structural schematic of the target protein was generated. The pathogenicity of the variants was classified based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature on the B3GALT6 gene variants leading to EDSSPD2 was retrieved from CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases. The procedures followed in this study were reviewed and approved by the Medical Ethics Committee of Affiliated Hospital of Guangdong Medical University (Ethics No.：PJ2021-097). RESULTS: The proband was a 2-year-old male with an onset in infancy. The main clinical manifestations included loose skin, scoliosis and kyphosis, generalized hypermobility of joints, and motor developmental delay. WES has revealed two compound heterozygous variants of the B3GALT6 gene (NM_080605.4): c.766C>T (p.Arg256Trp) and c.962G>A (p.Cys321Tyr). Sanger sequencing verification showed that the c.766C>T and c.962G>A variants were respectively derived from his phenotypically normal father and mother. Bioinformatics analysis showed that for the c.766C>T (p.Arg256Trp) variant, the Arg256 site is located within the galactosyltransferase catalytic domain (GalT domain) of the β3GalT6 protein. According to the ACMG guidelines, the c.766C>T variant was classified as a likely pathogenic (PS3+PM2_supporting+PM3+PP3), and the c.962G>A was classified as a variant of unknown significance (PM2_Supporting+PM3+PP3). By following the pre-set literature retrieval strategy, a total of 12 articles related to B3GALT6 gene variants were identified (11 English and 1 Chinese), which involved a total of 71 patients. Among these, 4 reports (involving 20 patients) involved B3GALT6 gene variants leading to EDSSPD2. Among the 18 live-born EDSSPD2 patients (including the proband in this study), common clinical manifestations have included scoliosis (88.9%, 16/18), generalized hypotonia (83.3%, 15/18), and soft and lax skin (66.7%, 12/18). Some patients already showed skeletal abnormalities on prenatal ultrasound scan (22.2%, 4/18), while a few presented with cervical instability (16.7%, 3/18). One child had deceased at 18 months of age due to hypoxia caused by tracheomalacia and tracheal compression due to scoliosis. Among the 23 reported EDSSPD2 related B3GALT6 variant sites, missense variants were the most common (78.3%, 18/23), followed by nonsense variants (21.7%, 5/23). CONCLUSION Above finding has enriched the clinical and mutational spectra of EDSSPD2. Early genetic testing has important clinical value for the diagnosis, differential diagnosis, and genetic counseling of this disease.
Humans ; Male ; Ehlers-Danlos Syndrome/genetics* ; Pedigree ; N-Acetylgalactosaminyltransferases/genetics* ; Asian People/genetics* ; DNA Copy Number Variations ; Exome Sequencing ; Female ; Child ; Child, Preschool ; Phenotype ; Mutation ; China ; East Asian People ; Galactosyltransferases

BACKGROUND:Conducting mental fatigue research in sports depends on appropriate mental fatigue induction tasks.However,the different types and time settings for the tasks in this field have interfered with the selection and determination of the appropriate task for mental fatigue research. OBJECTIVE:To compare the effects of three mental fatigue tasks and their commonly used time settings for mental fatigue induction. METHODS:In this randomized crossover study,16 male amateur soccer players performed four tasks of 60-minute duration with an interval≥48 hours in a randomized counter-balanced order:STROOP task(psychological cognition group),social media use in smartphone(electron exposure group),whole-body coordination task(exercise group)and emotionally neutral video watching as controls(control group).Before each task,the visual analogue scale(VAS)-motivation,VAS-mental fatigue,VAS-physical fatigue,and average heart rate were measured.Also,the VAS-mental fatigue,VAS-mental exertion,VAS-physical fatigue,and average heart rate were recorded every 15 minutes during the task.Repeated measures analysis of variance was mainly used for statistical analysis. RESULTS AND CONCLUSION:The baseline level of VAS-mental fatigue in the four groups were similar(P=0.806).(2)The VAS-mental fatigue of the psychological cognition group at 30,45 and 60 minutes was significantly higher than that of the other three groups(all P＜0.05).The VAS-mental fatigue of psychological cognition,electron exposure,and exercise groups at 45 minutes were similar with that at 60 minutes(all P＞0.05),but significantly higher than that of pretest,15 minutes and 30 minutes(all P＜0.05).To conclude,the psychological cognition task is superior to the electron exposure and exercise tasks for mental fatigue induction and 45 minutes is the appropriate length of time to effectively induce mental fatigue.

BACKGROUND:Knee osteoarthritis is a common disease in middle-aged and elderly people.It is a kind of disease that seriously affects the quality of life of patients and even has the risk of disability.Therefore,the pathogenesis and treatment of knee osteoarthritis have become the focus of research.In Chinese medicine,knee osteoarthritis is often treated as"biness,"which is closely related to"biness"caused by blood stasis and blood vessels blocking collaterals in the theory of"blood stasis"in traditional Chinese medicine.Iron overload is a kind of pathological state caused by iron metabolism disorder,which highly coincides with the pathogenic characteristics and clinical manifestations of the"blood stasis"theory of traditional Chinese medicine,and is a risk factor that promotes the development of knee osteoarthritis. OBJECTIVE:Based on the"blood stasis"theory,to summarize the effects of iron overload on cartilage metabolism and subchondral bone reconstruction,to lay a new theoretical foundation for the treatment of knee osteoarthritis with traditional Chinese medicine,and to explore the therapeutic effect of traditional Chinese medicine for promoting blood circulation after interfering with bone tissue. METHODS:CNKI,WanFang database,PubMed and Web of Science databases were searched for relevant literature.The Chinese search terms were"ferroptosis,iron,iron overload,osteoarthritis,blood stasis"and the English search terms were"ferroptosis,iron,iron overload,osteoarthritis,TCM."In the end,76 articles were included for further review. RESULTS AND CONCLUSION:First of all,we explored the potential of the"blood stasis"theory in treating knee osteoarthritis,and found that"blood stasis"is a crucial part in the progress of knee osteoarthritis,indicating that the"blood stasis"theory is the key to the treatment of knee osteoarthritis in traditional Chinese medicine.Secondly,"blood stasis"and iron overload have a high degree of similarity in pathogenic factors,clinical manifestations,and pathogenic characteristics,suggesting the possibility of"blood stasis"theory in treating iron overload.This finding reminds us that iron overload may be an important mechanistic basis for the"blood stasis"theory in the treatment of knee osteoarthritis.The extracts of blood-activating drugs can relieve iron overload and treat knee osteoarthritis,but the specific mechanism is still unclear.Therefore,we believe that the relationship between"blood stasis"theory and iron overload and related mechanisms are important research directions for knee osteoarthritis in the future.The related mechanism of"blood stasis"theory to alleviate iron overload and then treat knee osteoarthritis also provides a theoretical basis for the modernization of traditional Chinese medicine,such as the development of new drugs and innovative usage,and has certain guiding significance for clinical practice.

Loganin(LOG),a bioactive compound derived from Cornus officinalis Siebold & Zucc,has been understudied in the context of osteoarthritis(OA)treatment.In this study,we induced an inflammatory response in chondrocytes using lipopolysaccharide(LPS)and subsequently treated these cells with LOG.We employed fluorescence analysis to quantify reactive oxygen species(ROS)levels and measured the expression of NLRP3 and nuclear factor erythropoietin-2-related factor 2(NRF2)using real-time quantitative polymerase chain reaction(qRT-PCR),Western blotting,and immunofluorescence(IF)techniques.Additionally,we developed an OA mouse model by performing medial meniscus destabilization(DMM)surgery and monitored disease progression through micro-com-puted tomography(micro-CT),hematoxylin and eosin(H&E)staining,safranin O and fast green(S&F)staining,and immunohisto-chemical(IHC)analysis.Our results indicate that LOG significantly reduced LPS-induced ROS levels in chondrocytes,inhibited the activation of the NLRP3 inflammasome,and enhanced NRF2/heme oxygenase 1(HO-1)signaling.In vivo,LOG treatment mitigated cartilage degradation and osteophyte formation triggered by DMM surgery,decreased NLRP3 expression,and increased NRF2 expres-sion.These findings suggest that LOG has a protective effect against OA,potentially delaying disease progression by inhibiting the ROS-NLRP3-IL-1β axis and activating the NRF2/HO-1 pathway.

Objective To explore the effect of acute caffeine and theanine supplementation on coordi-nation and aerobic performance in mentally fatigued soccer players.Methods A randomized crossover de-sign was employed with 15 male amateur soccer players.Participants underwent three different interven-tions—caffeine(caffeine group),theanine(theanine group),and placebo(placebo group)—with a one-week washout period between each intervention.After each supplementation,participants performed a 45-minute Stroop task to induce mental fatigue,followed by a speed dribbling test(SDT)and the 30-15 intermittent fitness test(30-15IFT)to assess coordination and aerobic performance,respectively.Mea-surements included visual analog scale for mental fatigue(VAS-MF),motivation(VAS-MO),Brunel mood scale for fatigue(BRUMS-F)and vigor(BRUMS-V)pre-and post-Stroop task,response time(RT),response accuracy(ACC),average heart rate(HRave)during Stroop,mental exertion(VAS-ME)post-Stroop,rating of perceived exertion(RPE),HRave,and peak heart rate(HRpeak)during SDT and 30-15IFT.All data were analyzed using repeated measures ANOVA.Results The change in VAS-MF(ΔVAS-MF)before and after the Stroop task was lower in the caffeine group compared to the placebo group(P=0.064),while the theanine group showed similar ΔVAS-MF to the latter group(P=0.999).Both the caffeine and theanine groups had significantly faster RT(P=0.003 and 0.033,respectively)and higher ACC(P=0.006 and 0.033,respectively)during the Stroop task compared to the placebo group.Moreover,coordination performance in both the caffeine and theanine groups was better than the placebo group(P=0.096 and 0.078,respectively).Meanwhile,aerobic performance in the caffeine group was significantly better than the placebo group[time to exhaustion(TTE):P=0.012;last stage ve-locity of 30-15IFT(VIFT):P=0.007;maximal oxygen uptake(VO2max):P=0.008],whereas no significant differences were found between the theanine group and the placebo group in the aerobic performance(TTE:P=0.999;VIFT:P=0.999;VO2max:P=0.999).Conclusion Both acute caffeine and theanine supple-mentation can mitigate the negative effect of mental fatigue on coordination performance in soccer play-ers.Additionally,acute caffeine supplementation can also alleviate the negative impact of mental fa-tigue on aerobic performance.

Nuclear receptor corepressor (NCoR1) interacts with various nuclear receptors and regulates the anabolism and catabolism of lipids. An imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome development. In this study, we found that the deletion of NCoR1 in intestinal epithelial cells (IECs) mainly activated the nuclear receptor PPARα and attenuated metabolic syndrome by stimulating thermogenesis. The increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate, whose production was significantly enhanced by PPARα activation in the fed state. Additionally, NCoR1 deletion derepressed intestinal LXR, increased cholesterol excretion, and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity, thereby reversing the possible negative effects of intestinal PPARα activation. Therefore, the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Objective To explore the clinical and pathological features, diagnosis and treatment of eosinophilic cystitis in children. Method The clinical data of 7 patients with eosinophilic cystitis admitted from 2012 to 2016 were retrospectively analyzed, and the related literature were reviewed. Results The median age of the 7 patients was 9 years, and clinical manifestations were urgent urination, frequent micturition, odynuria, hematuria, abdominal pain and nocturnal enuresis. Ultrasonography and CT examination showed thickened bladder wall and space occupying lesions.All the 7 children received bladder biopsy, and pathology was consistent with eosinophilic cystitis. Six of them were cured after 2 months of drug therapy, and the other one was cured by repeated drug treatment for 1 year.All patients were followed up for 3 months to 4 years until the abnormal symptoms of voiding disappeared and the abnormal changes of bladder disappeared by imaging examination. Conclusion Eosinophilic cystitis in children is a benign lesion, having extremely similar clinical manifestations to bladder tumor. Without biopsy, the diagnosis of eosinophilic cystitis can also be made according to the clinical manifestation, laboratory examination and treatment effect. The treatment for this disease mainly includes hormone, antihistamine and anti-inflammatory drugs.

Objective To investigate the effect of intermittent fasting on metabolize and gut microbiota in obese presenium rats fed with high-fat-sugar-diet. Methods We fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and the rats for intermittent fasting were selected base on their body weight. The rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was performed and fasting blood samples and fecal samples were collected for measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4 tags using Illumina. Gut microbial community structure was analyzed with QIIME and LEfSe. Results After the intervention, the body weight of the fasting rats was significantly lower than that in high-fat diet group (P<0.01). OGTT results suggested impairment of sugar tolerance in the fasting group, which showed a significantly larger AUC than compared with the high-fat diet group (P<0.05). Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05) and partially restored liver steatosis, and improved the gut microbiota by increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely correlated with the weight of the rats. Conclusion Intermittent fasting can decrease the body weight and blood lipid levels and restore normal gut microbiota but can cause impairment of glucose metabolism in obese presenium rats.

Objective To investigate the effect of intermittent fasting on metabolize and gut microbiota in obese presenium rats fed with high-fat-sugar-diet. Methods We fed the Wistar rats with high-fat and high-sugar diet to induce adiposity, and the rats for intermittent fasting were selected base on their body weight. The rats were subjected to fasting for 72 h every 2 weeks for 18 weeks. OGTT test was performed and fasting blood samples and fecal samples were collected for measurement of TC, TG, HDL-C and LDL-C and sequence analysis of fecal 16S rRNA V4 tags using Illumina. Gut microbial community structure was analyzed with QIIME and LEfSe. Results After the intervention, the body weight of the fasting rats was significantly lower than that in high-fat diet group (P<0.01). OGTT results suggested impairment of sugar tolerance in the fasting group, which showed a significantly larger AUC than compared with the high-fat diet group (P<0.05). Intermittent fasting significantly reduced blood HDL-C and LDL-C levels (P<0.05) and partially restored liver steatosis, and improved the gut microbiota by increasing the abundance of YS2, RF32 and Helicobacteraceae and reducing Lactobacillus, Roseburia, Erysipelotrichaceae and Ralstonia. Bradyrhizobiaceae was found to be positively correlated with CHOL and HDL-C, and RF39 was inversely correlated with the weight of the rats. Conclusion Intermittent fasting can decrease the body weight and blood lipid levels and restore normal gut microbiota but can cause impairment of glucose metabolism in obese presenium rats.