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 investigate the therapeutic efficacy of Zhi Long Huoxue Tongyu Capsules combined with Edaravone in the treatment of patients with ischemic cerebrovascular disease(ICVD)of qi deficiency and blood stasis syndrome,and to explore their effect on serum levels of soluble cluster of differentiation 40 ligand(sCD40L),lipoprotein phospholipase A2(Lp-PLA2),and glycated albumin(GA).Methods A total of 117 patients with ICVD of qi deficiency and blood stasis syndrome were randomly divided into control group 1,control group 2,and study group,with 39 patients in each group.The three groups were all given basic treatment with agents of diuretic,lipid regulation,antiplatelet,and antihypertensive,and additionally,control group 1 was given Edaravone,control group 2 was given Zhi Long Huoxue Tongyu Capsules,and the study group was given Zhi Long Huoxue Tongyu Capsules combined with Edaravone.The course of treatment for the three groups covered 14 days.Before and after treatment,the three groups were observed in the changes of National Institutes of Health Stroke Scale(NIHSS)scores for neurological function,modified Barthel Index(MBI)scores for activities of daily living(ADL),cerebral hemodynamics indicators[peak systolic velocity(PSV),end-diastolic velocity(EDV),mean velocity(Vm),pulsatility index(PI),and resistance index(RI)],neurofactors[neuron-specific enolase(NSE),S100β protein(S100β),and myelin basic protein(MBP)],vascular endothelial function indicators[von Willebrand factor(VWF),endothelin 1(ET-1),and nitric oxide(NO)],and levels of serum sCD40L,Lp-PLA2,and GA.After treatment,the clinical efficacy and the incidence of adverse reactions among the three groups of patients were compared.Results(1)After 14 days of treatment,the total effective rate of the study group was 94.87%(37/39),which was significantly higher than that of control group 1[71.79%(28/39)]and control group 2[76.92%(30/39)],the differences being statistically significant(P<0.05).No statistically significant difference was shown between control group 1 and control group 2(P>0.05).(2)After treatment,the cerebral hemodynamics indicators of PSV,EDV,Vm,and PI of the middle cerebral artery(MCA)in the three groups were increased compared with those before treatment(P<0.05),and the RI was decreased compared with that before treatment(P<0.05).The increase of PSV,EDV,Vm,and PI of the MCA and the decrease of RI in the study group were significantly superior to those in control group 1 and control group 2(P<0.05).No statistically significant differences in PSV,EDV,Vm,PI,and RI of MCA were shown between control group 1 and control group 2 after treatment(P>0.05).(3)After treatment,the serum sCD40L,Lp-PLA2,and GA levels in the three groups were decreased compared with those before treatment(P<0.05),and the decrease in the study group was significantly superior to that in control group 1 and control group 2(P<0.05).However,the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(4)After treatment,the serum levels of neurofactors of NSE,S100β,and MBP in the three groups were all decreased compared with those before treatment(P<0.05),and the decrease of the serum levels in the study group was significantly superior to that in control group 1 and control group 2,while the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(5)After treatment,the vascular endothelial function indicators of serum vWF and ET-1 levels in the three groups were decreased compared with those before treatment(P<0.05),and the serum NO level was increased compared with that before treatment(P<0.05).The decrease of serum vWF and ET-1 levels and the increase of serum NO level in the study group were significantly superior to those in control group-1 and control group-2(P<0.05),while the difference of serum vWF,ET-1 and NO levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(6)After treatment,the NIHSS scores for neurological function in the three groups were decreased(P<0.05)and the MBI scores for ADL were increased(P<0.05)compared with those before treatment,and the decrease of the NIHSS scores and the increase of the MBI scores in the study group was significantly superior to those in control group 1 and control group 2(P<0.05),while and the differences of NIHSS and MBI scores after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(7)The incidence rate of adverse reactions was 15.38%(6/39)in the study group,7.69%(3/39)in the control group 1,and 12.82%(5/39)in the control group 2,and the pairwise comparison between groups showed that the difference was not statistically significant(P>0.05).Conclusion Zhi Long Huoxue Tongyu Capsules combined with Edaravone exert certain efficacy in the treatment of patients with ICVD of qi deficiency and blood stasis syndrome,and the combined therapy is effective on improving blood circulation,restoring neurological function,enhancing the ADL,with higher safety.Its therapeutic mechanism may be related to the improvement of the vascular endothelial function,and the down-regulation of serum levels of neurofactors of NSE,S100 β,MBP,and serum expression levels of sCD40L,Lp-PLA2,and GA.

Objective To explore the effect of Sanshen Shuxin Decoction combined with Huan-gqi Injection in the treatment of coronary heart disease(CHD)and its impacts on left ventricular function and Rho kinase(ROCK)expression.Methods A total of 120 CHD patients admitted to our hospital from August 2021 to August 2023 were selected as study subjects and randomly divided into three groups,with 40 patients in each group using a random number table method.All three groups received basic treatment.On this basis,control group 1 received Sanshen Shuxin Decoction,control group 2 received Huangqi Injection,and the combined group received both Sanshen Shuxin Decoction and Huangqi Injection.The treatment effects,occurrence of angina pectoris,hemorheo-logical parameters[fibrinogen(FIB),low-shear blood viscosity,erythrocyte aggregation index,high-shear blood viscosity],blood lipid indicators[total cholesterol(TG),triglycerides(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],car-diac function[stroke volume(SV),cardiac output(CO),left ventricular ejection fraction(LVEF)],ROCK activity,and occurrence of adverse reactions were compared among the three groups.Results The total effective rate of treatment in the combined group was higher than that in control group 1 and control group 2(P＜0.05).After 14 days of treatment,the frequency of angina pectoris episodes decreased and the duration of episodes shortened in all three groups compared with before treatment,and the combined group had a lower frequency and shorter duration of angina pec-toris episodes than control group 1 and control group 2(P＜0.05).There were no statistically sig-nificant differences in the frequency and duration of angina pectoris episodes between control group 1 and control group 2 after 14 days of treatment(P＞0.05).After 14 days of treatment,FIB level,e-rythrocyte aggregation index,low-shear blood viscosity,and high-shear blood viscosity decreased in all three groups compared with before treatment,and the combined group had lower values than con-trol group 1 and control group 2(P＜0.05).There were no statistically significant differences in these hemorheological parameters between control group 1 and control group 2 after 14 days of treat-ment(P＞0.05).After 14 days of treatment,TG,TC,and LDL-C levels decreased in all three groups compared with before treatment,and the combined group had lower levels than control group 1 and control group 2.HDL-C levels increased in all three groups compared with before treatment,and the combined group had higher HDL-C level than control group 1 and control group 2(P＜0.05).There were no statistically significant differences in TG,TC,LDL-C,and HDL-C levels be-tween control group 1 and control group 2 after 14 days of treatment(P＞0.05).After 14 days of treatment,LVEF,CO,and SV increased in all three groups compared with before treatment,and the combined group had higher values than control group 1 and control group 2(P＜0.05).There were no statistically significant differences in LVEF,CO,and SV between control group 1 and con-trol group 2 after 14 days of treatment(P＞0.05).Before treatment,ROCK activity was(61.28±7.15)％in the combined group,(60.85±5.93)％in control group 1,and(60.61±6.27)％in control group 2,with no statistically significant difference among the three groups(P＞0.05).After 14 days of treatment,ROCK activity decreased in all three groups compared with before treatment,and the combined group had lower ROCK activity than control group 1 and control group 2(P＜0.05).ROCK activity was(40.18±5.03)％in the combined group,(48.24±6.29)％in con-trol group 1,and(47.79±6.12)％in control group 2 after 14 days of treatment.There was no sta-tistically significant difference in ROCK activity between control group 1 and control group 2 after 14 days of treatment(P＞0.05).There was no statistically significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion Sanshen Shuxin Decoction combined with Huangqi Injection has a significant effect in the treatment of CHD patients.It can im-prove patients'prognosis and ensure treatment safety,demonstrating high clinical value.

Colorectal cancer (CRC), as one of the most common gastrointestinal malignancy, is original from the epithelial/endothelial cells of colorectal tissues. CRC is one of the highest incidence and mortality rates of any malignancy in humans today. Moving forward the early diagnosis window of colorectal cancer, dynamic monitoring of the risk of postoperative recurrence and metastasis, early intervention is of great value in improving the diagnosis and treatment outcome of colorectal cancer. The clinical diagnosis of CRC via circulating tumor cells (CTC) has been considered as one of the fast, noninvasive, reproducible liquid biopsy methods, and it has been widely used in the early diagnosis, treatment monitoring and prognosis evaluation of colorectal cancer. This review systematically expounded the applied research values of CTC counting, protein expression (phosphatase of regenerating liver-3, matrix metalloproteinase, etc), molecular characterization (adenomatous polyp of colon, erb-b2 receptor tyrosine kinase, etc), mRNA expression profile and single cell sequencing in the diagnosis and treatment of colorectal cancer, in order to assist clinical in rational use of CTC monitoring indicators and provide support for improving the prognosis of colorectal cancer.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Purpose To investigate the diagnostic criteria and value of angle parameters in female stress urinary incontinence (SUI),and to provide an objective basis for clinical diagnosis of SUI.Materials and Methods In retrospective analysis,138 patients with SUI diagnosed by clinic from December 2014 to December 2016 were selected as the study group,while 100 normal females receiving the routine medical examination were selected as the control group.All subjects in both groups were examined by pelvic floor ultrasound to observe the urethral inclination angle,urethral rotation angle (URA) and posterior urethrovesical angle (PUVA) to obtain the standard in diagnosis of female SUI.30 SUI patients from January to February 2017 were prospectively analyzed,and the above results were verified to evaluate their value in the diagnosis of SUI.Results There was no significant difference in age,body mass index,gravidity and parity history and resting state PUVA between the two groups (P＞0.05).There was significant difference in the resting state urethral inclination angle,Valsalva urethral inclination angle,PUVA and URA between the two groups (P＜0.05).The receiver operating characteristic curve was used to find the cut-off value of SUI:urethral inclination angle in resting state ＜14.5°,urethral inclination angle in Valsalva state ＞32.5 °,and URA ＞49.5 °,PUVA ＞154.5 °,with their sensitivity of 62％,73％,67％ and 57％,respectively;the specificity of 61％,84％,82％ and 70％,respectively;and the area under the curve of 0.633,0.809,0.768 and 0.658,respectively.By verification,when the urethral inclination angle was 14.5° in the resting state,the coincidence rate of the diagnosis of SUI was 63％;when the urethral inclination angle of Valsalva was 32.5°,83％;when the URA was 49.5°,77％;when the PUVA was 154.5 °,60％.Conclusion Pelvic floor ultrasound can clearly observe angle parameters of females,the determination of the cut-off value of ultrasound is helpful for clinical diagnosis and evaluation of SUI,and the urethral inclination angle in Valsalva state and URA are of high diagnostic value in the diagnosis of female SUI,providing an objective basis for clinical diagnosis of SUI.

OBJECTIVE: To evaluate the effectiveness of recombinant adenovirus p53 injection (rAd2p53) combined with cisplatin plus 5-fluorouracil regimen in treating laryngeal carcinoma. METHOD: Tumour animal models were established in the back of mice with Hep-2 cell line. Recombinant adenovirus p53 injection (rAd2p53) were transduced to tumor-bearing mouse by direct intratumoral injection combine with cisplatin plus 5-fluorouracil ivgtt. The control group 1 was given recombinant adenovirus p53 injection (rAd2p53) simplex. The control group 2 was administered with cisplatin plus 5-fluorouracil ivgtt simplex. Then compare the diameters of pro-treatment with that of post-treatment and test group with controls. RESULT: Tumor growth was significantly inhibited following combined rAd2p53 gene therapy with cisplatin plus 5-fluorouracil chemotherapy compared to single rAd2p53 gene therapy and cisplatin plus 5-fluorouracil chemotherapy controls. CONCLUSION Local injection of rAd2p53 combined with cisplatin plus 5-fluorouracil chemotherapy is a promising treatment to laryngeal cancer.
Adenoviridae ; genetics ; Animals ; Drug Evaluation, Preclinical ; Female ; Genes, p53 ; Genetic Therapy ; Genetic Vectors ; Laryngeal Neoplasms ; therapy ; Mice ; Mice, Inbred C3H ; Neoplasms, Experimental