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 establish the reference interval of serum non-high-density lipoprotein cholesterol(n-HDL-C)in adults in Yan'an city of Shaanxi Province and analyze the influencing factors.Methods A total of 16 921 adults from 10 towns in Yan'an City of Shaanxi Province from January to September 2023 were selected by random sampling.Age,sex,smoking,drinking,exercise,hypertension,diabetes,dyslipidemia,chronic disease,residence,eating habits,marital status,education and monthly income were investigated.Height,weight,waist circumference and blood pressure were measured.Serum triglyceride(TG),total cholesterol(TCHO),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),Apolipoprotein A1(ApoA1),Apolipoprotein B(ApoB)and lipoprotein a[Lp(a)]levels were detected,and n-HDL-C levels were calculated:n-HDL-C(mmol/L)=TCHO(mmol/L)-HDL-C(mmol/L).The 95％reference interval(P25～P97 5)was calculated according to the percentile method recommended in WS/T402-2012 Health Industry Standard of the People's Republic of China.Multivariate logistic regression was used to analyze the influencing factors of serum n-HDL-C level.Results The serum n-HDL-C levels in both males and females were not normally distributed(S=2.119,2.091,all P＜0.001).There were significant differences in serum levels of n-HDL-C among males aged＞60 years old[2.98(2.50,3.37)mmol/L],18～30 years old[2.84(2.49,3.26)mmol/L],31～40 years old[2.98(2.62,3.42)mmol/L],41～50 years old[3.10(2.62,3.47)mmol/L]and 51～60 years old[3.05(2.64,3.46)mmol/L]contrast,and the differences were significant(H=3.618～5.680,all P＜0.05).There were significant differences in serum levels of n-HDL-C among women aged 51～60 years[3.08(2.71,3.44)mmol/L],18～30 years[2.64(2.29,3.07)mmol/L],31～40 years[2.67(2.31,3.08)mmol/L]and 41～50 years old[2.94(2.58,3.29)mmol/L]contrast(H=8.161～13.445,all P＜0.001).There were significant differences in serum n-HDL-C levels among patients aged＞60 years old[2.98(2.57,3.34)mmol/L],18～30 years old,31～40 years old and 41～50 years old contrast,and the differences were significant(H=7.985～14.018,all P＜0.001).The reference interval of serum n-HDL-C level in adult population was obtained by combining the age groups with no statistical significance:males aged 18～60 years old(1.97～3.97mmol/L),＞60 years old(1.86～3.91mmol/L);females aged 18～50 years(1.82～3.74 mmol/L),＞50 years old(1.94～3.88 mmol/L).A total of 16 921 adults were divided into normal n-HDL-C group and abnormal group,and the differences of serum TG(1.02±0.31 mmol/L vs 1.24±0.37mmol/L),TCHO(3.97±1.02 mmol/L vs 4.66±1.25 mmol/L),LDL-C(2.37±0.58mmol/L vs 2.59±0.67 mmol/L)levels and age(43.55±11.52 years vs 46.27±8.13 years)between the two groups were significant(t=2.041～3.151,all P＜0.05),in which the abnormal rate of serum n-HDL-C level was 42.50％.Multivariate Logistic regression analysis showed that males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors for serum n-HDL-C levels in adults in this region(all P＜0.05).Conclusion The reference interval of serum n-HDL-C level in adults in this area was preliminarily established.Males,lack of exercise,overweight or obesity,dyslipidemia,urban residents,and high school education or above were the influential factors of abnormal serum n-HDL-C levels in adults in this area.

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.

Gestational diabetes mellitus (GDM) is a serious threat to maternal and infant health. However, the unclear etiology and pathogenesis of GDM is the harrier of clinical intervention. In recent years, the relationship between inflammation and GDM has been widely concerned, but the conclusions are inconsistent. This paper summarizes the research progress on the association between inflammation-related indicators and GDM, in order to provide a basis for the diagnosis, treatment, or prophylaxis of GDM.

Objective To analyze the correlation between the prevalence of chronic non-communicable diseases (NCDs) and fall incidence among the elderly in urban and rural areas in Chongqing, and to provide evidence for targeted intervention. Methods In 2019, a questionnaire survey was conducted among the elderly aged 65 and over in four districts and counties using multistage stratified cluster random sampling. The difference of NCDs prevalence and fall incidence was compared by Chi-square test. The correlation between NCDs and fall incidence was analyzed by multivariate logistic regression. Results A total of 806 and 801 elderly people aged 65 and above in urban and rural areas，respectively, were investigated The fall incidence among the elderly in rural areas (12.98%) was higher than that in urban areas (7.94%) (χ2=10.916, P=0.001). The multivariable logistic regression analysis showed that the prevalence of heart disease (OR=2.988, 95%CI:1.544-5.785), osteoporosis (OR=2.696, 95%CI:1.527-4.760) and vestibular dysfunction or deafness (OR=3.180, 95%CI:1.142-8.861) was associated with fall incidence among urban elderly people. Factors including need for care (OR=2.315，95%CI：1.130-4.744), diabetes (OR=3.067，95%CI:1.634-5.756), osteoporosis (OR=1.972, 95%CI:1.210-3.214), and arthritis (OR=2.975, 95%CI:1.901-4.657) were associated with fall incidence among rural elderly people. Conclusion The fall incidence among the elderly in rural areas is higher than that in urban areas in Chongqing. The prevalence of NCD is high among the elderly. Timely treatment of NCDs should be provided to reduce fall incidence among the elderly.

Objective To investigate the current situation of animal injury among children in Chongqing, and to provide a scientific basis for relevant departments to formulate and implement strategies and measures to prevent and control animal injury to children. Methods According to the method of multi-stage stratified cluster sampling, 14,056 children in grades 4-12 in four districts of Chongqing were selected as the investigation subjects, and the occurrence of animal injuries in the past 6 months was investigated. Results The incidence of animal injury among school children in Chongqing was 0.35% and the incidence of person-time was 0.36%. The incidence rate in males (0.48%) was higher than that in females (0.31%). The incidence rate in urban children (0.43%) was higher than that in rural children (0.30%). The incidence of animal injury was the lowest in nuclear families (0.25%), and the highest in single-parent families (0.82%). There were statistically significant differences in the incidence of animal injuries in children among different fathers' occupational types, family types and parents' parenting styles (P<0.05).  The main place of child animal injury was home (57.14%). Recreational activities were the main cause of animal injury (51.02%). The main injuries were lower limbs (42.86%), upper limbs (24.49%) and head (10.20%). Conclusion The prevention and control of children's animal injury in Chongqing should focus on boys and families. It is suggested to take targeted and comprehensive interventions to prevent animal injuries in children.

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.