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 effect of low-dose aspirin combined with dydrogesterone in the treatment of patients with polycystic ovary syndrome (PCOS) complicated with infertility and its influence on hormones and helper T cytokines.Methods:300 PCOS patients with infertility in the Second Affiliated Hospital of Air Force Military Medical University were selected from January 2018 to October 2023. A prospective randomized controlled study was performed. The study subjects were divided into control group and observation group by random envelope method, with 150 cases in each group. The control group was treated with dydrogesterone on the basis of routine intervention, while the observation group was combined with low-dose aspirin on the basis of the control group. The efficacy, pregnancy rate, hormones, Th1 and Th2 cytokines and incidence of adverse reactions were compared in between groups. Measurement data with normal distribution was represented by xˉ± s. Comparison between groups was performed by two-sample t-test and paired t-test was used for comparison before and after treatment. Enumeration data was represented by n(%). Comparison between groups was performed by χ2 test. Results:After treatment, the total effective rate of treatment and pregnancy rate in observation group were higher than those in control group [86.00%(129/150) vs. 74.67% (112/150), 63.33% (95/150) vs. 47.33% (71/150)] ( χ2=6.10, P=0.014, χ2=6.73, P=0.010). Serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in both groups were lower after treatment than those before treatment, and the levels in observation group were lower than those in control group [(5.27±1.01) U/L vs. (6.40±1.13) U/L, (6.78±0.87) U/L vs. (7.16±0.91) U/L], and serum estradiol level was higher than that before treatment, and the level in observation group was higher compared to control group [(93.35±8.17) ng/L vs. (82.45±9.14) ng/L] ( t=9.13, 3.70, 10.89, all P<0.001). After treatment, serum γ-interferon, interleukin (IL-2), IL-4 and IL-6 levels were all lower in both groups than those before treatment, and the above levels were lower in observation group than those in control group [(56.96±4.64) ng/L vs. (61.36±4.41) ng/L, (38.74±7.43) ng/L vs.(45.63±8.64) ng/L, (41.03±7.06) ng/L vs. (43.36±8.12 ng/L), (23.14±4.33) ng/L vs. (27.14±5.14) ng/L] ( t=8.42, 7.40, 2.65, 7.29, P<0.001, <0.0 010.008, <0.001). There was no statistical significance in the total incidence rate of adverse reactions between observation group and control group [12.67%(22/150) vs. 9.33% (14/150), χ2=0.85, P=0.356]. Conclusions:Low-dose aspirin combined with dydrogesterone has a significant clinical effect in the treatment of PCOS with infertility, and it can improve 3-month pregnancy rate, and effectively regulate hormones levels and Th1 and Th2 cytokines, and it will not increase adverse reactions, with high safety.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To compare minimally invasive surgery with traditional open surgery, analyze the current application status of health economic evaluations in the treatment of digestive tract cancers, such as esophageal cancer, gastric cancer, and colorectal cancer by minimally invasive surgery and provide evidence for the rational selection of clinical treatment, alleviation of disease-related economic burdens, and rational allocation of healthcare resources.Methods:By using five databases, i.e. China National Knowledge Infrastructure, Wanfang data, Chinese Biomedical Literature Database, PubMed, and Embase, a database was established to retrieve all the papers about health economic studies of minimally invasive surgery for esophageal cancer, gastric cancer, and colorectal cancer published until December 31, 2023. Literature was analyzed by using software NoteExpress 3.8, and data were processed using Excel 2021. The quality of included papers was evaluated using the CHEERS 2022 checklist, and Meta-analysis was conducted by using software Stata 17.0.Results:A total of 10 919 relevant papers were retrieved, and 59 studies were included. Only 14 studies (23.7%) used standard health economic evaluation methods. Meta-analysis results revealed no significant differences in direct medical expenditure and total expenditure between minimally invasive surgery and open surgery. However, the expenditure for minimally invasive surgery exhibited a significant increase [mean difference ( MD)=5 973.12 yuan, P<0.001], while hospital stay and indirect expenditure significantly decreased ( MD: -4.85 days and -733.79 yuan, P<0.001). In China, for gastric cancer, the direct medical expenditure of endoscopic surgery was lower than that of open surgery ( MD=-33 000.00 yuan) with no significant difference ( P<0.001). In colorectal cancer cases, the direct medical and surgical expenditures for laparoscopic surgery were higher than those for open surgery ( MD: 4 277.94 yuan and 4 267.80 yuan, P<0.001), while the indirect and total medical expenditures decreased ( MD: -768.34 yuan and -159.10 yuan). Hospital stays in patients who had minimally invasive surgery for all three types of cancer were shorter than those who had open surgery ( P<0.001). Conclusions:In the treatment of gastrointestinal cancer, compared with open surgery, minimally invasive surgery shows higher expenditure, but has advantages, such as shorter hospital stay and lower indirect expenditure, and there were no significant differences in direct medical and total expenditures between the two approaches. When conducting health economic evaluation, factors such as postoperative complications, hospital stay, and patient's economic status should be considered for their impact on total medical expenditure. It is necessary to pay attention to the application of health economic evaluations in healthcare decision-making.

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.

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.