Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Objective: To explore the network structure of eating behaviors with anxiety, depression and perceived stress in adolescents, so as to provide a basis for effective prevention and intervention of eating behavior problems and negative emotions in adolescents. Methods: Based on the Psychology and Behavior Investigation of Chinese Residents (2021) database, the study was conducted among 3 087 adolescents. Sakata Eating Behavior Scale Short From(EBS-SF) was used to investigate their eating behaviors. The Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder Scale-7 Item(GAD-7), and Perceived Stress Questionnaire-3 Item (PSQ-3) were used to evaluate their depression, anxiety and perceived stress. Network analysis method was applied to construct a network of eating behaviors and negative emotional symptoms among adolescents, so as to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total scores of eating behaviors, depression,anxiety and stress perception in adolescents were 17.41±4.53,6.95±6.08,4.86±5.03,9.34±3.80,respectively. The symptom with the highest intensity and expected impact was "I am only satisfied when I buy more food than I need", with a node intensity and expected impact value of 4.37. The nodes Depression and Anxiety were the most closely connected(weight=0.87). There were no statistically significant differences in the network structure( M =0.13,0.11) and network connection strength(female and male:4.16,4.06, s =0.10;urban and rural areas:4.08,4.07, s =0.01) between different sexes and residents ( P >0.05). Conclusion The negative impact of comorbidities such as anxiety, depression, perceived stress and eating behaviors among adolescents can be reduced through targeted prevention and intervention of core symptoms and bridging symptoms.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.

Objective:To investigate the characteristics of weight gain in the mid and late pregnancy of women with early pregnancy weight loss, and the relationship between weight gain and weight gain rate before the diagnosis of gestational diabetes mellitus (GDM) and GDM.Methods:A retrospective study was conducted on 2 614 singleton pregnant women who underwent prenatal care and delivered at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, from January 2014 to December 2021, and whose weight decreased compared to pre-pregnancy weight by 16 weeks of gestation. The rate of weight gain in mid and late pregnancy, also weight gain and weight gain rate at each stage were analyzed. Multivariate logistic regression was used to analyze the impact of total weight gain and weight gain rate at each stage before the diagnosis of GDM on the risk of GDM.Results:The rates of weight gain in mid and late pregnancy for women with early pregnancy weight loss who were underweight, normal weight, overweight, and obese before pregnancy were (0.60±0.15), (0.59±0.18), (0.53±0.20), and (0.42±0.20) kg/week, respectively, all higher than the "Chinese Recommended Standards for Weight Gain During Pregnancy" [which are (0.37-0.56), (0.26-0.48), (0.22-0.37), and (0.15-0.30) kg/week, respectively]. The weight gain rates at each stage of mid and late pregnancy in women with early pregnancy weight loss showed a "bimodal" trend, with the first peak in weight gain rate occurring at 16-20 or 20-24 weeks of gestation [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.75 kg/week (0.44-1.00 kg/week), 0.74 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.39-0.86 kg/week), and 0.50 kg/week (0.25-0.74 kg/week), respectively] and the second peak occurring at 28-32 weeks [weight gain rates for underweight, normal weight, overweight, and obese women before pregnancy were 0.63 kg/week (0.50-1.00 kg/week), 0.63 kg/week (0.38- 0.88 kg/week), 0.60 kg/week (0.25-0.88 kg/week), and 0.50 kg/week (0.22-0.75 kg/week). As of 28 weeks and 36 weeks of gestation, 53.7% (1 404/2 614) and 77.4% (1 946/2 512) of pregnant women, respectively, reached the lower limit of the recommended weight gain for the corresponding gestational weeks. No association was found between insufficient weight gain ( aOR=0.828, 95% CI: 0.639-1.071, P=0.151) or excessive weight gain ( aOR=0.936, 95% CI: 0.598-1.465, P=0.773) before the diagnosis of GDM and the risk of GDM. However, obese women with a weight loss greater than 5% of their pre-pregnancy weight in early pregnancy and a rapid weight gain rate (> P 75) between 16-20 weeks of gestation had an increased risk of developing GDM ( aOR=32.870, 95% CI: 1.625-664.775, P=0.023). Conclusions:In clinical practice, dynamic monitoring of weight changes at various stages of pregnancy in women who lose weight in early pregnancy is recommended. Targeted weight management during mid-pregnancy for women who are obese before pregnancy and experience significant weight loss in early pregnancy may help prevent excessive gestational weight gain and decrease the risk of GDM.

Objective:To describe the clinical manifestations, genetic mutation site, diagnosis, and treatment of a patient with multisystem proteinopathy type 1 (MSP1) caused by valosin-containing protein ( VCP) gene mutation, and to improve clinicians′ understanding of this disease. Methods:A retrospective analysis was performed on clinical and genetic data from a confirmed VCP gene missense mutation-associated MSP1 case diagnosed at the Department of Neurology, Affiliated Zhongda Hospital, School of Medicine, Southeast University in January 2024. A 12-month follow-up and systematic literature review were performed for comprehensive analysis. Results:The 53-year-old male patient presented with progressive limb weakness over 7 months. Neurological examination demonstrated tongue fasciculations, asymmetric proximal muscle weakness in all four limbs, left patellar hyperreflexia, positive right Chaddock sign, and bilateral Hoffmann signs. Electrophysiological studies demonstrated extensive neurogenic damage. Lower-limb muscle magnetic resonance imaging (MRI) showed selective fatty infiltration in specific muscle groups. Biceps brachii biopsy pathology revealed rimmed vacuoles and grouped atrophy of typeⅡfibers. Immunofluorescence confirmed aberrant aggregation of VCP within atrophic myofibers, showing co-localization with p62 and transactive response DNA binding protein 43 (TDP-43). Whole-genome sequencing identified a heterozygous c.463C>T (p.Arg155Cys) missense mutation in exon 5 of the VCP gene, classified as a likely pathogenic mutation according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The patient was diagnosed with MSP1 with amyotrophic lateral sclerosis and inclusion body myopathy as the main clinical manifestation based on clinical manifestations, electrophysiology, imaging, histopathology, and genetic findings. After 12 months of riluzole therapy, disease progression remained relatively slow. Literature review identified 67 relevant articles, revealing 87 VCP mutation genotypes and 19 clinical phenotypes. Conclusions:MSP1 is a genetically and phenotypically heterogeneous spectrum of multisystem degenerative disorders. This case represents the first reported VCP-related MSP1 in China, characterized by amyotrophic lateral sclerosis combined with inclusion body myopathy. Riluzole treatment demonstrates slowed disease progression over 1 year.

Objective:To investigate the relationship between the early pregnancy triglyceride-glucose (TyG) index and gestational diabetes mellitus (GDM) in twin pregnancies.Methods:This retrospective study involved twin-pregnant women who visited Beijing Obstetrics and Gynecology Hospital, Capital Medical University from October 2015 to February 2021. Based on the results of the 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks of gestation, the women were divided into the GDM and the control groups. The groups were further stratified based on maternal age (<35 years or ≥35 years), pre-pregnancy body mass index (BMI) (<24.0 or ≥24.0 kg/m2), and conception method [assisted reproductive technology (ART) or natural conception]. The correlation between early pregnancy TyG index and GDM, as well as the predictive value of the early pregnancy TyG index for the risk of GDM in twin pregnancies, were analyzed. The TyG index in early pregnancy was then divided into tertiles, and the risks of GDM in low, medium, and high TyG index groups were analyzed. Statistical analyses were performed using independent sample t-test, non-parametric test, Chi-square test, and binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the early pregnancy TyG index for GDM in twin pregnancies. Results:(1) A total of 1 684 twin-pregnant women were included, with an average age of 32.3 years (29.8-34.9 years) and a pre-pregnancy BMI of 22.0 kg/m2 (20.0-24.3 kg/m2). Among them, 319 (18.9%) were multiparas, 982 (58.3%) conceived through ART, and 357 (21.2%) were monochorionic twins. Of the 1 684 women, 367 (21.8%) were diagnosed with GDM (GDM group), whereas the remaining 1 317 were classified as the control group. (2) Compared to the control group, the GDM group had older maternal age [(32.2±3.7) years vs. (33.3±3.8) years, t=－4.92], higher pre-pregnancy weight, and BMI [57.5 kg (52.0-65.0 kg) vs. 60.0 kg (55.0-67.3 kg), U=279 901.50; 21.8 kg/m2 (19.8-24.0 kg/m2) vs. 22.9 kg/m2 (20.9-25.5 kg/m2), U=288 435.00]. The proportions of a family history of diabetes, history of GDM and polycystic ovary syndrome (PCOS) were all higher in the GDM group compared to the control group [9.6% (127/1 317) vs. 19.1% (70/367), χ 2=24.71; 0.8% (2/1 317) vs. 10.8% (8/367), χ 2=20.00; 9.1% (120/1 317) vs. 15.3% (56/367), χ 2=11.59] (all P<0.001). The GDM group had higher early pregnancy fasting blood glucose, triglyceride, and TyG indices compared to the control group [4.51 mmol/L (4.28-4.75 mmol/L) vs. 4.68 mmol/L (4.42-4.97 mmol/L), U=7.14; 1.23 mmol/L (0.93-1.57 mmol/L) vs. 1.43 mmol/L (1.09-1.89 mmol/L), U=4.81; 8.39±0.41 vs. 8.59±0.43, t=6.46]. The incidence of gestational anemia and weight gain were lower in the GDM group compared to the control group [39.2% (516/1 317) vs. 33.0% (121/367), χ 2=4.71; 17.0 kg (13.7-20.5 kg) vs. 15.0 kg (12.0-18.3 kg), U=187 966.00] (all P<0.05). The proportion of male newborns in the GDM group was higher than in the control group [52.5% (1 384/2 634) vs. 46.7% (343/734), χ 2=7.77, P=0.005]. (3) Early pregnancy TyG index was associated with GDM in twin pregnancies ( OR=3.164, 95% CI: 2.371-4.220, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, history of macrosomia, and family history of diabetes, the early pregnancy TyG index remained associated with GDM ( OR=2.560, 95% CI: 1.884-3.478, P<0.001). Analysis of the early pregnancy TyG index divided into tertiles (corresponding TyG indices of 8.25 and 8.59) revealed that, compared to those with a low TyG index, those with a mid TyG index had a 0.555-fold increased risk of GDM ( OR=1.555, 95% CI: 1.119-2.159, P=0.008), and those with a high TyG index had a 1.564-fold increased risk of GDM ( OR=2.564, 95% CI: 1.836-3.530, P<0.001). Stratified analysis by age, BMI, and mode of conception showed that the early pregnancy TyG index was associated with GDM in twin pregnancies (all P<0.001). (4) The threshold value for the early pregnancy TyG index to predict GDM in twin pregnancies was 8.33, with an area under the curve (AUC) of 0.632, 95% CI: 0.600-0.665, sensitivity of 0.744, and specificity of 0.436. The AUC in twin pregnancies for those who conceived via ART was 0.635 (95% CI: 0.593-0.676, P<0.001), slightly higher than in those who conceived naturally (AUC=0.628, 95% CI: 0.576-0.681, P<0.001). After adjusting for maternal age, pre-pregnancy BMI, history of GDM, and family history of diabetes, the AUC for the early pregnancy TyG index to predict GDM in twin pregnancies was 0.675 (95% CI: 0.644-0.707). For those who conceived via ART, the AUC (95% CI) was 0.675 (0.634-0.717), slightly lower than for those who conceived naturally [0.682 (0.632-0.733)] (all P<0.001). Conclusion:A high TyG index in the first trimester is a risk factor for GDM in twin pregnancies, but its predictive value for GDM in twin pregnancies needs further research to be confirmed.