Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Objective : To investigate the effects of immunoglobulin gene superfamily 10 (IGSF10) on prolifera- tion，migration and invasion of lung adenocarcinoma cells． Methods : ioinformatics was applied to study the ex- pression levels of IGSF10 in tumor tissues and normal tissues． Western blot and quantitative real-time PCR ( qPCR) were used to detect the expression level of IGSF10 in lung adenocarcinoma cell lines and normal lung epi- thelial cells．Knockdown of IGSF10，the effect of knockdown of IGSF10 on proliferation，migration and invasion of lung adenocarcinoma A549 cells was examined using cell counting kit-8 ( CCK-8) ，Transwell migration and inva- sion assay，scratch assay and plate cloning assay．The effects of knockdown of IGSF10 on the expression of invasion and migration-related genes in A549 cells were examined by Western blot and qPCR assays. Results : IGSF10 ex- pression in lung adenocarcinoma tissues was lower than that in normal tissues (P ＜0. 05) ．IGSF10 expression in lung adenocarcinoma cell lines was lower than that in lung epithelial cells (P＜0. 05) ．Knockdown of IGSF10 pro- moted the ability of lung adenocarcinoma A549 cells to proliferate ，proliferation ，migration and invasion ( P < 0. 05) ．Knockdown of IGSF10 promoted the expression of regulatory epithelial-mesenchymal transition marker Neu- ral-cadherin (N-cadherin) and key transcription factors Snail family transcriptional repressor 1 (Snail) and Snail family transcriptional repressor 2 (Slug) (P＜0. 05) and inhibited the expression of Epithelial-cadherin (E-cad- herin) (P＜0. 05) ． Conclusion Knockdown of IGSF10 may promote proliferation，migration and invasion of lung adenocarcinoma cells through activation of Snail，Slug / E-cadherin signaling axis，and this result may provide a po- tential new target for clinical diagnosis and treatment of lung adenocarcinoma.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective This study aims to establish a non-puerperal mastitis (NPM) rat model by simulating hyperprolactinemia and immune-inflammatory states, and to evaluate its local inflammatory characteristics in the mammary gland, thereby laying the foundation for research on the diagnosis and treatment of this clinically challenging disease. Methods Twelve SPF-grade Wistar female rats were evenly divided into a control group and a model group. During the experiment, the control group received no experimental treatment or medication. The model group received daily subcutaneous injections of 100 mg/kg metoclopramide hydrochloride for 7 consecutive days. Serum prolactin (PRL) levels were measured using ELISA on the 10th, 20th, and 30th days after the first injection. After 7 days of injections, 200 μL of lactating SD rat milk was mixed with 200 μL of complete Freund's adjuvant to prepare an oil-in-water emulsion, which was administered by multiple subcutaneous injections into the back of the Wistar rats for the initial immunization. Seven days after the initial immunization, the emulsion was injected subcutaneously into the third, fourth, and fifth mammary glands for the final immunization. After the final immunization, the rats were observed for 28 days for changes in mammary gland appearance, and the size of mammary nodules was calculated. On the 3rd, 7th, 14th, and 28th days, hematoxylin-eosin (HE) staining was used to analyze mammary tissue morphology. Immunohistochemistry was employed to detect CD138 expression levels. ELISA was used to measure the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) in mammary tissue to comprehensively assess the model. Results Rats in the model group exhibited mammary skin ulceration and foul odor at the ulcer sites. Palpation and ultrasound revealed the formation of mammary nodules. HE staining showed that on the 3rd day after the final immunization, normal ductal and lobular structures in the mammary glands disappeared, with significant infiltration of plasma cells. On the 7th day, ductal dilation, epithelial necrosis and detachment, and pronounced periductal plasma cell and lymphocyte (predominantly T-lymphocytes) infiltration were observed. On the 14th day, there was a proliferation of fibrofatty tissue, small blood vessels, and granulation tissue, with scattered plasma cells in the interstitium. By the 28th day, inflammatory cell infiltration and fibrous tissue proliferation were reduced, with granuloma formation. Serum PRL levels in the model group were significantly increased on the 10th day (P<0.05) and the 20th day (P<0.001). IL-6 and TNF-α levels in mammary tissue were higher in the model group compared to the control group on the 3rd, 7th, 14th, and 28th days (P<0.05). IL-1β levels were higher on the 3rd, 7th, and 14th days compared with the control group (P<0.01) but lower than the control group on the 28th day (P>0.05). iNOS levels were significantly higher on the 7th day after the final immunization (P<0.001). Conclusion A successful NPM model was established in rats, which exhibited typical pathological features such as local mammary masses, abscesses, ulcers, ductal dilation and plasma cell infiltration. This model can serve as a foundation for further research into the diagnosis and treatment of this clinically challenging disease.

Objective:To evaluate the quality of test papers and to analyze students'mastery of knowledge through the analysis of test papers,so as to provide reference for the reform of test proposition and correction teaching.Methods:Using paper analysis software(Ver 2.0),the paper quality,the students'scores and the answers to the questions of the final exam paper of Physiology of grade 2021 students majoring in nursing were analyzed.Results:The composition of the test paper was consistent with the requirements of the teaching programme,the difficulty of subjective and objective test questions was moderate,the differentiation of subjective test questions was good,the differentiation of objective test questions was general,and the reliability and validity were good.The overall performance was basically normal distribution.The full score ratio of objective test questions was higher than that of subjective test questions,and the zero score test questions were mostly concentrated in chapter 10 and chapter 4.Conclusion:Test paper analysis can feedback the problems and shortcomings of test paper proposition and teaching process,promote the quality of test paper and teaching model innovation,and improve the quality of teaching.

Objective:To analyze the predictive value of ultrasound blood flow parameters for postoperative cervical lymph node metastasis in thyroid cancer.Methods:Fifty-three patients with thyroid cancer who received medical treatment in Guang′anmen Hospital of China Academy of Chinese Medical Sciences from August 2020 to December 2022 were selected as the observation group, and 53 healthy patients who received physical examination in the physical examination center during the same period were selected as the healthy group. All of them were given ultrasound examination. The ultrasonic blood flow parameters including peak systolic flow velocity (PSV), pulsation index (PI), resistance index (RI) of the two groups were compared. The patients with thyroid cancer were divided into metastatic group (33 cases) and non-metastatic group (20 cases) according to the presence or absence of lymph node metastasis. The ultrasonic blood flow parameters, blood flow grading and ultrasonographic characteristics of the two groups were compared.Results:The levels of PSV in the observation group was higher than that in the health group, PI and RI were lower than those in the health group: (25.56 ± 5.25) cm/s vs. (14.52 ± 2.85) cm/s, 0.51 ± 0.13 vs. 0.63 ± 0.16, 0.82 ± 0.11 vs. 1.15 ± 0.24, there were statistical differences ( P<0.05). The levels of PSV in the metastatic group was higher than that in non-metastatic group, PI and RI were lower than those in the non-metastatic group: (29.65 ± 3.76) cm/s vs. (19.20 ± 2.96) cm/s, 0.48 ± 0.10 vs. 0.56 ± 0.05, 0.76 ± 0.13 vs. 0.91 ± 0.19, there were statistical differences ( P<0.05). The blood grade between the metastatic group and non-metastatic group had statistical difference ( P<0.05). The rates of blood flow signal disjointed, blood flow abundant, micro-calcification boundary unclear, internal echo uneven and the length-width ratio <2 in the metastatic group were higher than those in the non-metastatic group: 54.55%(18/33) vs. 25.00%(5/20), 78.79%(26/33) vs. 50.00%(10/20), 57.58%(19/33) vs. 20.00%(4/20), 66.67%(22/33) vs. 35.00%(7/20), 63.64%(21/33) vs. 30.00%(6/20), 63.64%(21/33) vs. 25.00%(5/20), there were statistical differences ( P<0.05). Conclusions:Abnormal ultrasonic blood flow parameters in patients with thyroid cancer are closely related to lymph node metastasis. Quantitative detection of ultrasonic blood flow parameters can provide a reliable reference for the evaluation of thyroid cancer.

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) μg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.
Male ; Humans ; Prostate/surgery* ; Prostatectomy/adverse effects* ; Prostatic Neoplasms/pathology* ; Urinary Incontinence/etiology* ; Laparoscopy/methods* ; Magnetic Resonance Imaging/adverse effects* ; Recovery of Function ; Retrospective Studies