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.

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.

OBJECTIVE To establish the quality standard of Triadica cochinchinensis and to perform the acute toxicity study. METHODS Appearance properties, powder microscopic identification, and thin-layer chromatography(TLC) identification were researched. The specific chromatogram was established by HPLC. The content of cadmium(Cd), lead(Pb), arsenic(As), copper(Cu), and mercury(Hg) was determined by inductively coupled plasma-mass spectrometry(ICP-MS). Acute toxicity was studied by maximum dose. RESULTS The outer skin of herbs was dark brown, and the inner surface was light yellow brown and fibrous. Besides, crystal sheath fiber was common, and calcium oxalate clusters arranges in rows. In the TLC diagram of the test product, the fluorescent spots of the same color were displayed at the corresponding position of the control product(scopoletin, isofraxidin). Five common peaks were calibrated in the characteristic map and the three characteristic peaks(scopoletin, isofraxidin, dimethylfraxetin) were recognized. The content of the measured heavy metal elements was lower than the national limit standard. The linear correlation coefficient was R2 > 0.999. The precision, stability, repetitive RSD were < 10%. The average recovery rate of the added sample was 80%−120%, and the RSD was < 10%. The maximum dose of the acute toxicity test was 184.09 g·kg−1. The 14 d internal body mass, food intake, organ-body ratios, the serum glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, blood urea nitrogen, and creatinine were not significantly different by comparing with the normal controls. Therefore, no significant toxicity was observed. CONCLUSION The established standard can provide a reference for evaluating the quality of Triadica cochinchinensis. The heavy metal content of ten batches of medicinal materials is within the safe range. Acute toxicity test show that there is no obvious significant adverse teactions after oral administration, and the safe dose range is large, which can provide a reference for the subsequent development and utilization.

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

Objective:To investigate the expression of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1(lncRNA MALAT1) in bronchopulmonary dysplasia (BPD) of neonatal rats induced by hyperoxia and its effect on alveolar type 2 epithelial cells (AEC Ⅱ).Methods:The lung injury model of neonatal SD rats induced by hyperoxia(model group, n=50, inhaled oxygen concentration of 80%-85%) and the control group(inhaled air, n=50) were prepared.Lung tissue samples were taken and retained on days 1, 3, 7, 14 and 21, and the physiological and pathological changes of lung tissue were detected by paraffin-embedded sections and hematoxylin-eosin staining; The dynamic expression of lncRNA MALAT1 in lung tissue was detected by real-time fluorescent quantitative polymerase chain reaction; The dynamic expression of surfactant protein C(SPC) in lung tissue and AECⅡ was detected by Western blot.AECⅡ was extracted from lung tissue of normal newborn rats, and lncRNA MALAT1 was knocked down by siRNA.The cells were collected and Western blot as well as immunofluorescence were used to detect the changes of SPC. Results:The lung tissue of model group gradually became thickened with alveolar compartments, and the alveolar cavity was enlarged with the disappearance of alveolar spine and other pathological structural changes.Compared with the control group, there was no difference in the expression of lncRNA MALAT1 and SPC in the lung tissue from model group on days 1, 3( P>0.05), but the expression of lncRNA MALAT1 and SPC significantly increased on days 7, 14 and 21( P<0.05). When lncRNA MALAT1 was inhibited, SPC expression showed a decrease trend. Conclusion:Hyperoxia can lead to the stagnation of lung development in neonatal rats, and the structure and function of alveolar disorders are impaired.The expression of lncRNA MALAT1 is involved in the process of hyperoxia-induced BPD in neonatal rats.The increase of lncRNA MALAT1 may promote the proliferation of AECⅡ.

Objective:To investigate expression level of transcriptional co-activator with PDZ-binding motif(TAZ) in neonatal rats with chronic lung diseases induced by hyperoxia and explore its potential role in the disease.Methods:The model of high-oxygen-induced lung injury in neonatal rats was established by continuous inhalation of high-concentration oxygen.The rats in experimental group inhaled 85% oxygen, while the rats in control group inhaled air.The lung tissues were collected at the 1st, 3rd, 7th, 14th and 21st day, and the lung tissue sections were stained with hematoxylin and eosin staining to observe the pathological changes of the lung.In addition, the dynamic expressions of TAZ, surfactant protein C(SPC) and aquaporin-5(AQP5) in lung tissue were detected by real-time PCR, western blot and immunohistochemistry staining.Results:In the experimental group, with the prolongation of oxygen inhalation time, we found that the alveolar cavity increased, the number decreased, the alveolar septum thickened, and the alveolar structure was simplified.Compared with the control group, there was no difference in TAZ, SPC and AQP5 expression at 1st and 3rd days in the lung tissue in the experimental group( P>0.05). However, at 7, 14 and 21 days, the expression of TAZ in mRNA and protein level in lung tissue in experimental group decreased significantly, and the expression of SPC in mRNA and protein level increased significantly, while the expression of AQP5 in mRNA and protein level decreased, the differences were all statistically significant( P<0.05). Conclusion:Hyperoxia can cause alveolar structure disorder and pulmonary arrested development in neonatal rat.The expression levels of SPC and AQP5 show that the injury of type Ⅰ alveolar epithelial cells (AEC Ⅰ) is severe.Although the number of type Ⅱ alveolar epithelial cells (AEC Ⅱ) increased, but its differentiation capacity decreased obviously.The decrease of TAZ expression may cause AEC Ⅱ lose the function of differentiation into AEC Ⅰ.

Objective To investigate the pattern of lymph node metastasis and analyze prognostic factors of Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods The retrospective case-control study was conducted.The clinicopathological data of 368 patients with Siewert type Ⅱ AEG who were admitted to Tianjin Medical University Cancer Institute and Hospital from June 2010 and November 2015 were collected.There were 323 males and 45 females,aged from 35 to 80 years,with an average age of 64 years.Of 368 patients,209 underwent left transthoracic surgery,1 12 underwent thoracoabdominal surgery,and 47 underwent Ivor-Lewis surgery.Observation indicators:(1) total lymph node metastasis and metastasis of various lymph node stations;(2) follow-up and survival;(3) prognostic factors analysis;(4) influencing factors affecting thoracic lymph node metastasis.Follow-up using outpatient examination and telephone interview was performed to detect survival of patients up to November 2018.Measurement data with skewed distribution were represented as M (range).Count data were represented as absolute number or percentage.The survival time and rate were calculated using the Kaplan-Meier method.The univariate and multivariate analyses were done by the COX proportional hazard model.Results (1) Total lymph node metastasis and metastasis of various lymph node stations:the total lymph node metastasis rate was 66.58％ (245/368) in 368 patients.The metastasis rates of abdominal lymph nodes,thoracic lymph nodes,lower mediastinal lymph nodes,and upper mediastinal lymph nodes were 65.49％ (241/368),12.77％ (47/368),12.23％ (45/368),and 1.09％ (4/368),respectively.The order of metastasis rate of various lymph node stations from high to low was 51.99％(170/237) of No.7 left gastric artery,34.23％(89/260) of No.1 right paracardial region,33.88％ (83/245) of No.2 left paracardial region,28.91％ (85/294) of No.3 lesser curvature,27.10％(29/107) of No.1 1 splenic artery,19.75％(16/81) of No.9 celiac trunk,15.25％(36/236) of No.E8Lo lower paraesophageal region,11.94％ (16/134) of No.4 greater curvature,11.76％ (6/51) of No.E8M middle paraesophageal region,11.1 1％(10/90) of No.8 common hepatic artery,4.65％(4/86) of No.E9L left inferior pulmonary ligament and 3.39％ (2/59) of No.E7 subcarinal region.(2) Follow-up and survival:of the 368 patients,309 were followed up for 1-103 months,with a median follow-up time of 38 months.The survival time of 309 patients was 0.7-101.9 months,and the median survival time was 35.9 months.During the followup,the postoperative l-,2-,3-year overall survival rates were 85.9％,68.6％,and 58.7％,respectively.(3) Prognostic factors analysis.Results of univariate analysis showed that tumor differentiation degree,presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,tumor diameter,and length of esophageal invasion were associated factors affecting prognosis of patients (x2 =8.776,26.582,46.057,18.679,22.460,9.158,P＜0.05).Results of multivariate analysis showed that presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter were independent influencing factors for prognosis of patients [odds ratio (OR) =1.699,1.271,1.422,1.238,95％ confidence interval:1.102-2.621,1.019-1.481,1.090-1.856,0.971-1.481,P＜0.05].(4) Influencing factors affecting thoracic lymph node metastasis:results of univariate analysis showed that tumor diameter,length of esophageal invasion,number of lymph lodes harvested in thorax were related factors for thoracic lymph node metastasis (x2 =5.129,43.140,10.605,P＜0.05).Results of multivariate analysis showed that length of esophageal invasion ≥2 cm,number of lymph lodes harvested in thorax ≥ 4 were independent risk factors for thoracic lymph node metastasis (OR =6.321,1.097,95％ confidence interval:2.982-13.398,1.026-1.173,P＜0.05).Conclusion Lymph node metastasis of Siewert type Ⅱ AEG spreads two regions,mainly at abdominal lymph nodes,followed by the thoracic lymph nodes.Presence of thoracic lymph node metastasis,number of metastatic lymph nodes,T staging,and tumor diameter are independent influencing factors for prognosis of patients.Presence of thoracic lymph node metastasis indicates poor prognosis of patients.Length of esophageal invasion ≥ 2 cm and number of lymph lodes harvested in thorax ≥4 are independent risk factors for thoracic lymph node metastasis.