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 evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

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 investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.

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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore the predictive value of the geriatric nutritional risk index (GNRI) for anesthesia related adverse reaction (ARAR) in elderly patients undergoing radical resection of colorectal cancer.Methods:The clinical data of 178 elderly patients undergoing radical resection of colorectal cancer from March 2020 to October 2023 in Mianyang Central Hospital were retrospectively analyzed. Among them, 48 cases had ARAR (ARAR group), and 130 cases did not experience ARAR (control group). The gender, age, body mass index, smoking history, alcoholism history, hypertension, diabetes, hyperlipidemia, tumor location, TNM stage, pathological type, preoperative intestinal obstruction, preoperative chemotherapy, operation mode, operation time, intraoperative bleeding, American Society of Anesthesiologists (ASA) grade, number of lymph node dissection and GNRI were recorded. The prognostic analysis indexes were recorded, including length of hospital stay, unplanned ICU transfer and in-hospital death. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of GNRI for ARAR in elderly patients undergoing radical resection of colorectal cancer. Multifactor Logistic regression analysis was used to analyze the independent risk factors of ARAR in elderly patients undergoing radical resection of colorectal cancer.Results:The age, ASA grade Ⅱ proportion and preoperative chemotherapy proportion in ARAR group were significantly higher than those in control group: (75.35 ± 6.43) years vs. (70.12 ± 5.94) years, 41.67% (20/48) vs. 22.31% (29/130) and 20.83% (10/48) vs. 4.62% (6/130), the GNRI was significantly lower than that in control group: 96.73 ± 6.23 vs. 106.21 ± 6.95, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in other indexes between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of GNRI for predicting ARAR in elderly patients undergoing radical resection of colorectal cancer was 0.832 (95% CI 0.770 to 0.894, P<0.01), with an optimal cutoff value of 100.5, sensitivity of 70.80%, and specificity of 75.00%. Multifactor Logistic regression analysis result showed that GNRI<98, age ≥80 years, preoperative chemotherapy and ASA grade Ⅱ were independent risk factors for ARAR in elderly patients undergoing radical resection of colorectal cancer ( OR = 2.372, 2.144, 2.708 and 3.280; 95% CI 1.108 to 5.069, 1.072 to 4.382, 1.180 to 6.136 and 1.072 to 9.882; P<0.01 or <0.05). The length of hospital stay and unplanned ICU transfer rate in ARAR group were significantly higher than those in control group: (14.58 ± 3.82) d vs. (11.94 ± 3.66) d and 22.92% (11/48) vs. 10.77% (14/130), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in in-hospital mortality between the two groups ( P>0.05). Conclusions:The GNRI is a predictive index of ARAR in elderly patients undergoing radical resection of colorectal cancer. For patients with nutritional risk, preoperative nutritional support should be strengthened to reduce the occurrence of ARAR.

Objective:To explore the predictive value of the geriatric nutritional risk index (GNRI) for anesthesia related adverse reaction (ARAR) in elderly patients undergoing radical resection of colorectal cancer.Methods:The clinical data of 178 elderly patients undergoing radical resection of colorectal cancer from March 2020 to October 2023 in Mianyang Central Hospital were retrospectively analyzed. Among them, 48 cases had ARAR (ARAR group), and 130 cases did not experience ARAR (control group). The gender, age, body mass index, smoking history, alcoholism history, hypertension, diabetes, hyperlipidemia, tumor location, TNM stage, pathological type, preoperative intestinal obstruction, preoperative chemotherapy, operation mode, operation time, intraoperative bleeding, American Society of Anesthesiologists (ASA) grade, number of lymph node dissection and GNRI were recorded. The prognostic analysis indexes were recorded, including length of hospital stay, unplanned ICU transfer and in-hospital death. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of GNRI for ARAR in elderly patients undergoing radical resection of colorectal cancer. Multifactor Logistic regression analysis was used to analyze the independent risk factors of ARAR in elderly patients undergoing radical resection of colorectal cancer.Results:The age, ASA grade Ⅱ proportion and preoperative chemotherapy proportion in ARAR group were significantly higher than those in control group: (75.35 ± 6.43) years vs. (70.12 ± 5.94) years, 41.67% (20/48) vs. 22.31% (29/130) and 20.83% (10/48) vs. 4.62% (6/130), the GNRI was significantly lower than that in control group: 96.73 ± 6.23 vs. 106.21 ± 6.95, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in other indexes between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of GNRI for predicting ARAR in elderly patients undergoing radical resection of colorectal cancer was 0.832 (95% CI 0.770 to 0.894, P<0.01), with an optimal cutoff value of 100.5, sensitivity of 70.80%, and specificity of 75.00%. Multifactor Logistic regression analysis result showed that GNRI<98, age ≥80 years, preoperative chemotherapy and ASA grade Ⅱ were independent risk factors for ARAR in elderly patients undergoing radical resection of colorectal cancer ( OR = 2.372, 2.144, 2.708 and 3.280; 95% CI 1.108 to 5.069, 1.072 to 4.382, 1.180 to 6.136 and 1.072 to 9.882; P<0.01 or <0.05). The length of hospital stay and unplanned ICU transfer rate in ARAR group were significantly higher than those in control group: (14.58 ± 3.82) d vs. (11.94 ± 3.66) d and 22.92% (11/48) vs. 10.77% (14/130), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in in-hospital mortality between the two groups ( P>0.05). Conclusions:The GNRI is a predictive index of ARAR in elderly patients undergoing radical resection of colorectal cancer. For patients with nutritional risk, preoperative nutritional support should be strengthened to reduce the occurrence of ARAR.

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 investigate the feasibility of simultaneous multi-slice(SMS)acquisition combined with single-shot echo-planar imaging(SSEPI)multi-model diffusion weighted imaging(DWI)for breast lesions.Methods Totally 108 cases of breast lesions were retrospectively enrolled and divided into malignant group(n=66)and benign group(n=42)based on pathology.3.0T MR scanner was used to acquire SSEPI and SMS-SSEPI multi-b values DWI,7 derived parameters were obtained through post-processing with mono-exponential,fractional-order calculus(FROC)and continuous-time random walk(CTRW)models.Then the imaging quality and derived parameters of SMS-SSEPI and SSEPI DWI were compared between groups.Spearman correlation analysis was performed to explore the relationships of corresponding parameters between SMS-SSEPI DWI and SSEPI DWI.Diagnostic performance of each parameter for distinguishing malignant and benign lesions was evaluated according to the area under the receiver operating characteristic curve(AUC).Results Background noise score of SMS-SSEPI DWI was lower than that of SSEPI DWI(P＜0.05),whereas no significant difference of overall imaging quality,normal anatomical structure depiction,lesion conspicuity,geometric distortion,signal-to-noise ratio(SNR)nor contrast-to-noise ratio(CNR)was found between SMS-SSEPI DWI and SSEPI DWI(all P＞0.05).Parameters derived from SMS-SSEPI DWI were all moderately to highly positively correlated with those from SSEPI DWI(rs=0.66-0.98).Malignant lesions exhibited significantly lower apparent diffusion coefficient(ADC),diffusion coefficient based on FROC(DFROC),fractional order derivative in space(βFROC),diffusion coefficient based on CTRW(DCTRW),temporal diffusion heterogeneity index(αCTRW)and spatial diffusion heterogeneity index(βCTRW)values,but higher spatial parameter(μFROC)value than benign lesions(all P＜0.05).AUC of SMS-SSEPI DWI derived parameters for differentiating malignant from benign lesions were 0.699-0.900,of those from SSEPI DWI were 0.654-0.887,while in both SMS-SSEPI DWI and SSEPI DWI,DFROC had the highest diagnostic efficacy(AUC=0.900,0.887).Conclusion SMS-SSEPI DWI could be used to effectively differentiate malignant and benign breast lesions.