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 characterize the seasonal patterns of influenza in Kunming City, Yunnan Province before, during, and after the COVID-19 pandemic, and provide scientific evidence for optimizing influenza prevention and control strategies. MethodsInfluenza-like illness (ILI) and etiological surveillance data for influenza from the 14^th week of 2010 to the 13^th week of 2024 in Kunming City of Yunnan Province were collected. Harmonic regression models were constructed to analyze the epidemic characteristics and seasonal patterns of influenza before (2010/2011‒2019/2020 influenza seasons), during (2020/2021‒2022/2023 influenza seasons), and after (2023/2024 influenza season) the COVID-19 pandemic. ResultsBefore the COVID-19 pandemic, influenza in Kunming City mainly exhibited an annual cyclic pattern without a significant semi-annual periodicity, peaking from December to February of the next year, with an epidemic duration of 20‒30 weeks. During the pandemic, influenza seasonality shifted, with an increase in semi-annual periodicity and an approximate one month delay in annual peaks. However, after the pandemic, the annual amplitude of influenza increased compared with that before the pandemic, and the epidemic duration extended by about one month. Although the annual peak largely reverted to the pre-pandemic levels, the annual peaks for different influenza subtypes/lineages had not fully recovered. ConclusionInfluenza seasonality in Kunming City underwent substantial alterations following the COVID-19 pandemic and has not yet fully reverted to pre-pandemic levels. Continuous surveillance on different subtypes/lineages of influenza viruses remains essential, and prevention and control strategies should be adjusted and optimized in a timely manner based on current epidemic trends.

Astragaloside Ⅳ （AS-Ⅳ） is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally， and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism， exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect， and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways， such as AMPK， NLRP3， NF-κB， JAK2/STAT3， and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.

OBJECTIVE To investigate the relationship between azimuth direction,angular intervals,and the accuracy of azimuthal sound source localization.METHODS Fifteen young subjects with normal hearing were tested using nine azimuth settings.The test results were presented as root mean square error and percentage confusion.RESULTS The confusion rate under high-frequency narrowband noise was significantly higher than that under broadband noise and three-syllable words.In the frontal direction,statistically significant differences were observed between the 20° and 10° intervals,as well as between the 20° and 15° intervals(P<0.05),but no significant difference was found between the 10° and 15° intervals(P>0.05).In the lateral and rear directions,statistically significant differences were found between the 30° and 15° intervals,as well as between the 30° and 20° intervals(P<0.05),but no significant difference was found between the 15° and 20° intervals(P>0.05).Statistically significant differences were observed between the frontal direction and both the lateral and rear directions(P<0.05),but no significant difference was found between the lateral and rear directions(P>0.05).CONCLUSION Using stimuli that contain broader bandwidth cues can more accurately reflect the subject's horizontal localization ability.For source azimuth identification tests using broadband noise and three-syllable words,it is recommended to use a 15° interval in the frontal direction,and a 20° interval in the lateral and rear directions.The frontal and lateral directions can be preferred for testing.

Objective:To analyze the differentially expressed messenger RNA(mRNA), microRNA(miRNA), and long non-coding RNA(lncRNA)during the browning of mouse subcutaneous adipose tissue, construct a competitive endogenous RNA(ceRNA)network, and provide a theoretical basis for investigating the regulatory mechanisms of white adipose tissue browning.Methods:A cold-stimulated mouse model was established for transcriptome sequencing.Bioinformatics tools were employed to screen for differentially expressed mRNAs, miRNAs, and lncRNAs.An integrated mRNA-miRNA-lncRNA analysis was performed to construct a ceRNA network.Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Gene Set Enrichment Analysis(GSEA)were conducted on the differentially expressed mRNAs and ceRNA networks to explore transcriptional regulation during the cold-induced browning of subcutaneous adipose tissue.Results:Transcriptomic analysis of the cold-stimulated model identified 4, 256 differentially expressed RNAs, which include 3, 600 mRNAs, 588 lncRNAs, and 68 miRNAs.GO and KEGG analyses revealed that the browning of white adipose tissue involves immune-related processes, such as immune system processes, immune responses, adaptive and innate immune responses, and the positive regulation of T-cell activation.A ceRNA network associated with browning regulation was constructed, comprising 233 nodes(188 mRNAs, 34 miRNAs, and 11 lncRNAs)and 351 edges.Protein-protein interaction(PPI)analysis of the mRNAs within the ceRNA network highlighted pathways including apoptosis, intracellular signaling transduction, hypoxia-inducible factor-1(HIF-1), AMP-activated protein kinase(AMPK), Janus kinase-signal transducer and activators of transcription(JAK-STAT)signaling, carbon metabolism, glycolysis, and thyroid hormone pathways, all of which regulate lipid metabolism, hypoxia, and glycolysis.Cytohubba analysis identified the top 10 hub genes: Bcl2, Src, Cebpb, Creb1, Runx1, Foxo3, Ets1, Socs3, Slc2 a4, and Pkm. Conclusions:The ceRNA network that regulates the browning of white adipose tissue is involved in various pathways, including carbon metabolism, glycolysis, thyroid hormone signaling, growth hormone signaling, prolactin signaling, as well as the HIF-1, AMPK, and JAK-STAT pathways.Key regulatory miRNAs in this context include miR-30e-5p, miR-182-5p, miR-20b-5p, miR-144-3p, miR-363-3p, miR-141-3p, miR-203-3p, and miR-107-3p.These miRNAs may serve as critical targets for inducing browning in response to cold exposure.

Objective:To observe the characteristics of multi-muscle surface electromyography (sEMG) network indices during static standing among hemiplegic stroke survivors, and to evaluate the value of the indices in assessing neuromuscular dysfunction.Methods:Ten male stroke survivors with hemiplegia were recruited into the hemiplegia group, and 10 age-matched healthy males were chosen as the control group. Both groups were required to perform 30s static standing tasks with their eyes open and closed. The sEMG signals from the bilateral gluteus maximus (GM), rectus femoris (RF) and biceps femoris (BF) muscles were synchronously collected. Linear time-frequency domain indices were then calculated from the sEMG signals, including the root mean square (RMS) and median frequency (MF). Network indices were extracted from the multiplex recurrence network and weighted networks were constructed from the sEMG signals, including the average interlayer mutual information (I), average edge overlap (ω), clustering coefficient (C), average shortest path length (L) and degree of centrality (DC).Results:With the eyes closed, the RMS values of the bilateral GMs of the hemiplegia group, as well as the values for the RF and BF on the unaffected side were significantly higher than the control group′s values. In the hemiplegia group, the RMS values of the RF and BF muscles on the unaffected side were significantly higher than on the affected side during standing with the eyes closed. For the RF muscles the RMS values on the unaffected side were, on average, significantly higher than with the eyes open. The MF of the GM muscles on the unaffected side in the hemiplegia group was significantly lower than the average MF values of the bilateral GM muscles in the control group with the eyes open or closed. With the eyes closed, the MF of the unaffected-side GM was significantly lower than that of the affected-side GM in the hemiplegia group. Compared with the control group, the hemiplegia group showed a significant increase in I and ω values, but a significant decrease in L values with the eyes open or closed. The DC values of the bilateral GM, RF and BF muscles in the hemiplegia group were significantly higher than among the control group with the eyes open, which was also true of the bilateral GM and RF muscles with the eyes closed. With the BF muscles it was true only of the unaffected side. In the hemiplegia group, the DC values of the unaffected-side GM with the eyes open or closed, and of the unaffected-side BF with the eyes closed.Conclusions:When standing still, hemiplegic stroke survivors exhibit increased overall synchronous muscle adjustment with involvement of unaffected-side muscles, especially the GM. sEMG network indices such as I, ω, L and DC can assess multi-muscle synchronous adaptability and the involvement of single muscles. sEMG network algorithms thus have potential as a new method for localizing and quantitatively assessing neuromuscular dysfunction among such patients.

Objective:This study evaluates the horizontal sound localization ability of young and middle-aged individuals with symmetric sensorineural hearing loss (SNHL) in noisy environments. It also examines the impact of hearing loss severity and signal-to-noise ratio (SNR) on localization accuracy.Methods:In this cross-sectional study, conducted from April 2023 to April 2024, 135 young and middle-aged patients (73 males and 62 females, aged 18-60 years) with SNHL who sought care at Beijing Chaoyang Hospital, were categorized into mild, moderate, and moderate-to-severe hearing loss groups (45 per group), with 45 normal-hearing controls (23 males and 22 females, aged 20-60 years). Participants completed localization tasks in quiet and noisy environments with SNR levels of 5 dB, 0 dB, -5 dB, and-10 dB. Root mean square error (RMSE) was used to measure localization accuracy. Repeated measures ANOVA assessed the effects of hearing loss and SNR on RMSE, while, Pearson correlation evaluated the relationship between binaural 4-frequency pure-tone average (4fPTA) and RMSE. Multiple linear regression analyzed the predictive role of 4fPTA and age.Results:(1) Two-way repeated measures ANOVA showed that both hearing loss severity and SNR significantly affected RMSE ( F=92.67, P<0.01; F=430.29, P<0.01), with a significant interaction between the two factors( F=92.67, P<0.01). (2) RMSE increased with hearing loss severity. At SNRs of 5 dB, 0 dB, and-5 dB, the moderate-to-severe group had significantly higher RMSE than the mild and moderate groups ( P<0.01). No significant differences were found between mild and moderate groups ( P=0.53, 0.57, 0.22). At-10 dB SNR, significant differences were observed across all groups ( P<0.01). (3) RMSE increased non-linearly as SNR decreased. Mean RMSE values under quiet conditions and at SNRs of 5 dB, 0 dB, -5 dB, and-10 dB were (7.43±5.01)°, (9.80±5.74)°, (11.60±6.22)°, (14.56±7.07)°, and (18.74±8.02)°, respectively. (4) RMSE was significantly positively correlated with binaural 4fPTA ( r=0.54-0.58, P<0.01). Multiple linear regression analysis indicated that the binaural average 4fPTA significantly predicted RMSE ( P<0.01), explaining 30.5%-34.1% of RMSE variance. Age did not significantly contribute to RMSE variation. Conclusions:The degree of hearing loss and background noise SNR significantly affect horizontal sound localization in young and middle-aged SNHL patients. RMSE increases with hearing loss severity and decreases with higher SNR. The interaction between hearing loss and SNR is significant, and RMSE correlates with binaural 4fPTA. However, the regression model based on 4fPTA and age explains only part of the RMSE variance, suggesting other contributing factors.

Objective:To analyze the epidemiological and clinical characteristics of pertussis cases identified through active surveillance.Methods:Active surveillance for pertussis was conducted in three sentinel hospitals in Yiwu, Zhejiang Province, and Yongcheng, Henan Province. The study population included cases that met the surveillance case definition and sought medical care at outpatient/emergency departments or were hospitalized between June 1, 2021, and May 31, 2022. Samples were collected for bacterial culture and PCR detection. Case information and clinical data were collected. Differences in rates were assessed using the chi-square test or Fisher's exact probability test, and the differences in cough time were compared using the Mann-Whitney U test. Results:Among 1 423 cases of pertussis surveillance, the positive rate of pertussis was 28.11% (400/1 423), with a median age of 5 years (interquartile range: 2, 8). The positive rate in Yongcheng, Henan Province, and Yiwu, Zhejiang Province were 39.27% (216/550) and 21.08% (184/873), respectively; the positive rate of pertussis was highest in July 2021, and the highest positive rate of pertussis was among those aged 10-14. The positive rate of pertussis in hospitalized cases was higher than in outpatient/emergency cases (26.68%) ( χ2=4.16, P=0.041). Among the 400 laboratory test-positive cases, the highest proportion of atypical symptom cases was in adults aged 20-59 (43.33%, 13/30). The specificity rates of apnea and worsening nocturnal cough in monitored cases under 3 months of age were 100.00% and 73.81%, respectively. Among monitored cases aged 3 months to 9 years, the proportions of symptoms including worsening nighttime cough (63.00%) and night sweats (4.59%) in test-positive cases were significantly higher than those in the test-negative group (47.77% and 0.56%, respectively), with statistically significant differences (both P<0.05). The specificity rates of worsened nighttime coughing and night sweats were 52.23% and 99.44%, respectively. Conclusions:The active surveillance results for pertussis showed that the 10-14 age group exhibited the highest positivity rate. Active surveillance enhanced the detection rate of pertussis. Among laboratory-confirmed cases, the proportion of atypical symptoms was the highest in adults, suggesting that laboratory testing should be combined to diagnose programs of pertussis. For infants under 3 months, worsening nighttime cough and apnea increase the diagnostic specificity, while for individuals aged 3 to 9 years old, worsening nighttime cough and night sweats increase the diagnostic specificity.

Objective:To explore the relationship between serum human epididymal secretory potein 4(HE4),carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199)levels with clinicopathological characteristics and prognosis of uterine fibroid patients.Methods:87 patients who were diagnosed with uterine fibroids in Xiamen Maternal and Child Health Hospital during the period of January 2019 to January 2024 were selected as the observation group,and 87 women who underwent health checkups during the same period were selected as the control group.The serum HE4,CEA and CA199 levels were detected and compared between the two groups before and 1 month after surgery.The relationship between serum HE4,CEA and CA199 levels before surgery and their clinicopathological characteristics was analyzed.The patients with uterine fibroids were followed up for 1 year after surgery,and they were divided into recurrence group and non-recurrence group according to the recurrence status,influencing factors of postoperative recurrence were analyzed by multiple logistic regression model,the predictive value of CEA,HE4,and CA199 for postoperative recurrence was analyzed by receiver operating characteristic(ROC)curves.Results:Serum HE4,CEA and CA199 levels before surgery in the observation group were significantly higher than those in the control group(P＜0.05).Serum HE4,CEA and CA199 levels before surgery in uterine fibroids patients were significantly correlated with breast hyperplasia,the location of the fibroids,the number of tumors and the maximum diameter of the fibroids(P＜0.05).87 patients with uterine fibroids were followed up for 1 year after surgery,with a recurrence rate of 26.44％.Serum HE4,CEA and CA199 levels at 1 month after surgery in the recurrence group were significantly higher than those in the non-recurrence group(P＜0.05).Elevated HE4,elevated CEA and elevatedCA199 were independent risk factors for postoperative recurrence in uterine fibroids patients(P＜0.05).The area under the curve(AUC)of combined prediction of CEA,HE4,and CA199 for predicting postoperative recurrence of uterine fibroma patients was 0.880.Conclusion:Serum HE4,CEA,and CA199 in uterine fibroids patients are abnormally elevated,and closely related to their clinicopathological characteristics.Serum HE4,CEA,and CA199 levles are influencing factors for postoperative recurrence in uterine fibroids patients and have good predictive value for postoperative recurrence.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.