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

By combining the origin and research progress of the combination of disease and syndrome, the core pathogenesis, this article explored the research ideas and methods of the core pathogenesis of TCM. It is found that modern TCM is mostly guided by the idea of classification-staging-syndrome differentiation, the main prescription of the main disease, the special prescription of the special disease, and the idea of "dynamic-fixed sequential". The tongue image syndrome differentiation method, clustering analysis method, drug test syndrome method, compound pathogenesis method, "evidence-based pathogenesis-syndrome treatment system" research model, and the integration of traditional Chinese and Western medicine theory were used to explore the core pathogenesis of TCM under the condition of disease. Combined with the advantages of modern medical disease differentiation and TCM syndrome differentiation, the individualized diagnosis and treatment methods of integrated traditional Chinese and Western medicine have been continuously improved, in order to solve the stage contradictions of different clinical stages, effectively delay the progression of the disease and improve the prognosis of the disease.

Objective To explore the mechanism by which curcumin improves behavioral deficits in mice with Parkinson's disease(PD)through fecal microbiota transplantation.Methods A subacute model of PD in mice was induced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Fecal microbiota from both the model group and the curcumin(Cur)-treated group(80 m g/kg)were collected and analyzed.The experiment involving fecal microbiota transplantation was structured into four distinct groups,fecal microbiota solvent transplantation group(FMTcon),model fecal microbiota transplantation group(FMTmodel),MPTP-induced model group(model),and model group subjected to fecal microbiota transplantation following curcumin treatment(model+FMTCur).The motor skills of the mice were assessed by using rod rotation,pole climbing experiment,and open field tests.Immunofluorescence techniques were employed to observe the expression tyrosine hydroxylase(TH)-positive neurons in the substantia nigra of the brain.Additionally,the gene expression of tumor necrosis factor-α(TNF-α)in the midbrain of mice was analyzed,alongside the protein expression of nuclear factor-κB(NF-κB)and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3).Results The subacute PD animal model in mice was successfully established,and fecal microbiota were separated and gathered.The model group exhibited significant motor impairment,as evidenced by a shortened rod rotation time(P＜0.05),prolonged pole climbing time(P＜0.05),significantly reduced total movement distance within the open field(P＜0.001),and decreased time spent in the central zone(P＜0.01).The relative expression level of TH+neurons in the substantia nigra was significantly reduced(P＜0.01).Moreover,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with significant elevations in protein expression of NF-κB(P＜0.001),phosphorylated NF-κB(p-NF-κB)(P＜0.01),NLRP3(P＜0.001),and Caspase-1(P＜0.01).The transplanted model microbial group(FMTmodel)also exhibited motor impairment,manifested by a trend of shortened rod rotation time,prolonged pole climbing time,a significant decrease in total movement distance within the open field(P＜0.01),and a trend of shortened time spent in the central zone.The relative expression level of TH+neurons in the substantia nigra decreased significantly(P＜0.05).Additionally,mRNA expression of TNF-α in the midbrain increased significantly(P＜0.01),along with notable elevations in the protein expression of NF-κB(P＜0.05),and Caspase-1(P＜0.01).Treatment with curcumin in the fecal microbiota transplantation group of mice(model+FMTCur)showed improvements in motor abilities,evidenced by shortened pole climbing time(P＜0.05),significantly prolonged rod rotation time(P＜0.01),and extended time spent in the central zone(P＜0.05).The relative expression level of TH+dopaminergic neurons in the substantia nigra increased significantly(P＜0.05).Moreover,mRNA expression of TNF-α in the midbrain decreased significantly(P＜0.01),along with notable reductions in the protein expression of NF-κB(P＜0.001),p-NF-κB(P＜0.01),NLRP3(P＜0.05),and Caspase-1(P＜0.01).Conclusion Fecal microbiota transplantation in PD model mice can induce behavioral deficits,damage TH+neurons in the substantia nigra,and trigger neuroinflammation in the brain.Subsequent curcumin treatment can ameliorate these deficits,reverse damage to TH+neurons,reduce neuroinflammatory factors,and decrease the expression of NF-κB and NLRP3 pathways.This preliminary evidence suggests that curcumin may improve Parkinsonian behavioral deficits in mice by modulating the gut microbiota.

Objective To establish a three-dimensional(3-D)structural mode-based nursing quality evaluation index system for the bleeding risk care in patients with deep venous thrombosis(DVT)of lower extremity receiving catheter-directed thrombolysis(CDT),so as to provide a reference for the normalization and standardization of bleeding risk care.Methods Based on the 3-D structural mode,through literature review,clinical practice research and group discussion,the first draft of nursing quality evaluation index system for CDT bleeding risk care was formulated.Using Delphi method,two rounds of letter inquiry were conducted,and the index content and index weighting were determined.Results The nursing quality evaluation index system included 3 level-Ⅰ indicators,11 level-Ⅱ indicators and 58 level-Ⅲ indicators.Two rounds of expert consultation were conducted,with 30 questionnaires for each round.The valid recovery rate of the questionnaire was 100.00％,indicating that expert's enthusiasm was higher.In the first round of letter inquiry,28 experts(93.3％)submitted suggestions for modification,and in the second round of letter inquiry,15 experts(50.0％)submitted suggestions for draft modification.The level of expert authority was as follows:the basis coefficient of expert judgment(Ca)was 0.93,the coefficient of expert familiarity with items(Cs)was 0.90,and the authority coefficient was 0.92.The degree of expert opinion coordination assessed by Kendall's harmony coefficient(Kendall's W)was 0.18-0.26(P＜0.05),and the coefficient of variation of each dimension was less than 0.15.Conclusion The nursing quality evaluation index system established in this study is scientific,reliable and practical.It can provide certain useful reference for the evaluation of CDT bleeding risk care quality.

Neuroscience is a significant frontier discipline within the natural sciences and has become an important interdisciplinary frontier scientific field. Brain is one of the most complex organs in the human body, and its structural and functional analysis is considered the “ultimate frontier” of human self-awareness and exploration of nature. Driven by the strategic layout of “China Brain Project”, Chinese scientists have conducted systematic research focusing on “understanding the brain, simulating the brain, and protecting the brain”. They have made breakthrough progress in areas such as the principles of brain cognition, mechanisms and interventions for brain diseases, brain-like computation, and applications of brain-machine intelligence technology, aiming to enhance brain health through biomedical technology and improve the quality of human life. Due to limited understanding and comprehension of neuroscience, there are still many important unresolved issues in the field of neuroscience, resulting in a lack of effective measures to prevent and protect brain health. Therefore, in addition to actively developing new generation drugs, exploring non pharmacological treatment strategies with better health benefits and higher safety is particularly important. Epidemiological data shows that, exercise is not only an indispensable part of daily life but also an important non-pharmacological approach for protecting brain health and preventing neurodegenerative diseases, forming an emerging research field known as motor neuroscience. Basic research in motor neuroscience primarily focuses on analyzing the dynamic coding mechanisms of neural circuits involved in motor control, breakthroughs in motor neuroscience research depend on the construction of dynamic monitoring systems across temporal and spatial scales. Therefore, high spatiotemporal resolution detection of movement processes and movement-induced changes in brain structure and neural activity signals is an important technical foundation for conducting motor neuroscience research and has developed a set of tools based on traditional neuroscience methods combined with novel motor behavior decoding technologies, providing an innovative technical platform for motor neuroscience research. The protective effect of exercise in neurodegenerative diseases provides broad application prospects for its clinical translation. Applied research in motor neuroscience centers on deciphering the regulatory networks of neuroprotective molecules mediated by exercise. From the perspectives of exercise promoting neurogenesis and regeneration, enhancing synaptic plasticity, modulating neuronal functional activity, and remodeling the molecular homeostasis of the neuronal microenvironment, it aims to improve cognitive function and reduce the incidence of Parkinson’s disease and Alzheimer’s disease. This has also advanced research into the molecular regulatory networks mediating exercise-induced neuroprotection and facilitated the clinical application and promotion of exercise rehabilitation strategies. Multidimensional analysis of exercise-regulated neural plasticity is the theoretical basis for elucidating the brain-protective mechanisms mediated by exercise and developing intervention strategies for neurological diseases. Thus,real-time analysis of different neural signals during active exercise is needed to study the health effects of exercise throughout the entire life cycle and enhance lifelong sports awareness. Therefore, this article will systematically summarize the innovative technological developments in motor neuroscience research, review the mechanisms of neural plasticity that exercise utilizes to protect the brain, and explore the role of exercise in the prevention and treatment of major neurodegenerative diseases. This aims to provide new ideas for future theoretical innovations and clinical applications in the field of exercise-induced brain protection.

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 preliminarily assess the horizontal sound localization and its influencing factors in patients with unilateral sudden sensorineural hearing loss during the acute phase.METHODS The azimuth discrimination test and azimuth identification test were completed,with the speech sound(65 dB SPL)as the stimulus.The minimum audible angle(MAA)and root-mean-square error(RMSE)were obtained,and the RMSE of the affected side and the healthy side were calculated respectively.According to the WHO(2021)hearing loss classification criteria,the data were analyzed based on the pure-tone average(PTA)of the affected ear.And the best resident hearing at each frequency of the affected ear was recorded.RESULTS The performance of the unilateral sudden sensorineural hearing loss patients in the sound localization varied greatly.Some performed close to the normal level,while others completely lost the ability to localize sound.The RMSE of the moderate hearing loss group(≥35 dB HL)was significantly higher than that of the normal hearing group(P<0.01),the MAA of the moderate to severe hearing loss group(≥50 dB HL)showed statistically significant differencescompared with normal hearing group(P<0.001).The RMSE of the affected side of patients in the severe and above hearing loss group was significantly larger than that of the healthy side.Regression analysis showed that the best resident hearing at each frequency of the affected ear was the most significant factor affecting MAA(R2=0.572,P<0.001)and RMSE(R2=0.768,P<0.001).CONCLUSION The horizontal sound localization of unilateral sudden sensorineural hearing loss patients in the acute phase varies greatly.When the PTA of the affected side reaches moderate hearing loss,the localization ability is significantly lower than that of normal-hearing individuals.The best resident hearing at each frequency of the affected ear is the key factor affecting the localization ability.

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 explore the role of PTPN11 gene polymorphisms in Noonan syndrome (NS) and other related diseases and to evaluate the association between PTPN11 gene variants and various disease phenotypes.Methods:This study first described a case of 7-year-old girl diagnosed with Nonan symdrome who visited our department in Februay 2024 presented to our department six months ago and was diagnosed with Noonan syndrome. Whole-exome sequencing revealed a heterozygous variant in her PTPN11 gene, with the single nucleotide polymorphism (SNP) locus identified as rs121918457. Due to limited phenotypic data associated with rs121918457 in available databases, the cis-expression quantitative trait locus (cis-eQTL) rs12425405, located near the PTPN11 gene, was used as a proxy to further investigate the impact of PTPN11 gene expression regulation on various disease phenotypes. A PheWAS analysis was conducted to assess the statistical association between PTPN11 polymorphism and diverse phenotypic traits. All data were analyzed using the PheWeb online tool, and statistical significance was tested using the P-value. Bonferroni correction was applied for multiple comparisons to ensure the reliability of the results. The significance level was set at P<0.05, and the Bonferroni-corrected significance threshold was P=3.52×10 -5. Results:This case demonstrated that, in addition to the typical clinical features of Noonan syndrome, the child also presented with significant hypertension and autoimmune symptoms (such as joint pain, peripheral nerve damage, and positive antinuclear antibodies). The PheWAS analysis revealed significant statistical associations between the rs12425405 polymorphism and the following disease phenotypes: myocardial infarction ( P=1.90×10 -5), coronary atherosclerosis ( P=7.40×10 -5), ischemic heart disease ( P=2.30×10 -5), and hypertension ( P=8.8×10 -5). Additionally, rs12425405 showed statistical associations with some autoimmune symptoms (such as rheumatoid arthritis) ( P=0.027), but did not reach the corrected significance threshold ( P>3.52×10 -5). Conclusion:PTPN11 gene mutations are not only pathogenic factors in Noonan syndrome but may also play a critical role in the development of cardiovascular diseases and are associated with autoimmune symptoms. However, further research is needed to elucidate the functional mechanisms of the PTPN11 gene across multiple diseases and determine whether common genetic drivers are present.

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.