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.

ObjectiveTo analyze the drug resistance and the molecular typing characteristics through pulsed field gel electrophoresis (PFGE) of Campylobacter spp. isolated from patients with infectious diarrhea in Baoshan District of Shanghai, and to provide a basis for Campylobacter spp. prevention and control and clinical medication. MethodsCampylobacter spp. was isolated, cultured and identified from stool samples of diarrheal patients collected from medical institutions at two monitoring sites in Baoshan District from 2019 to 2022. Antimicrobial susceptibility testing for 12 antibiotics was conducted on the isolated Campylobacter jejuni (C. jejuni) and Campylobacter. Coli (C. coli), and molecular typing was performed using PFGE. ResultsA total of 179 strains of Campylobacter spp. were isolated from 1 786 samples of diarrheal patients, with a positive rate of 10.02%. The highest resistance rate of C. jejuni was to ciprofloxacin (98.63%), followed by tetracycline (97.26%) and nalidixic acid (89.73%). C. coli was completely resistant to ciprofloxacin and nalidixic acid (100.00%), followed by tetracycline (90.91%). The multidrug resistance rates of C. jejuni and C. coli were 89.73% and 100.00%, respectively. 142 strains of C. jejuni produced 122 PFGE bands, while 33 strains of C. coli produced 33 PFGE bands, and the distribution of the bands was relatively dispersed. ConclusionFrom 2019 to 2022, the detection rate of Campylobacter in diarrheal patients was relatively high in Baoshan District of Shanghai, the multidrug resistance rate of Campylobacter isolates from diarrheal patients was relatively serious, in addition, the drug resistance pattern was complex, and the PFGE band pattern displayed a polymorphic distribution.

To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Background::Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.Methods::The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.Results::In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.Conclusions::In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Objective:To evaluate the safety and effectiveness of laparoscopic ventral mesh rectopexy (LVMR) +anal sphincter plasty for complete rectal prolapse.Methods:From Jan 1, 2018 to Dec 31, 2022, 45 patients with complete rectal prolapse diagnosed in Beijing Erlong Road Hospital received laparoscopic ventral mesh rectopexy +anal sphincter plasty were included in this study.Result:There was no mortality rate associated with LVMR in this study cohort. The follow-up period was 8-76 months, with a median follow-up period of 59 months. There were 2 cases of recurrence, with a recurrence rate of 4%. Patients with concomitant fecal incontinence symptoms had a preoperative Jorge Wexner fecal incontinence score of 13.8±2.0, and postoperative Jorge Wexner fecal incontinence scores of 7.5±1.5, 5.3±1.3, 4.3±1.1, 2.8±1.0, and 1.8±0.5 at 3, 6, 12, 36, and 60 months, respectively, all P<0.001. Patients with concomitant constipation had a preoperative Wexner constipation score of 15.7 ± 1.5, and a postoperative Wexner constipation score of 9.0±1.8, 6.8±1.5, 5.2±1.4, 4.1±0.7, 2.0±0.0 at 3, 6, 12, 36, and 60 months, respectively, all P<0.001. Conclusions:LVMR +anal Sphincter plasty is safe and effective for the treatment of complete rectal prolapse, and there are few complications related to biological patches. Anal sphincter plasty can effectively improve anal function.

Objective:To explore the clinical effect of a modified surgical procedure for replantation of severed digit-tips in Tamai zones I-II.Methods:From November 2019 to October 2022, the Department of Hand and Foot Microsurgery of the First Affiliated Hospital of Bengbu Medical College employed a modified procedure (to abandon the anatomically labelling of blood vessels and nerves after naked-eye debridement and fracture fixation, then perform the microscopic dissections and anastomoses of blood vessels and nerves, and the anastomosis of dorsal veins though an auxiliary small incision by the lateral nail fold of the severed digit-tip) to replant severed digit-tips in Tamai zones I-II of 26 patients (29 digits). The patients were 20 males (23 digits) and 6 females (6 digits), aged 3-66 years old, with mean age at 28 years old. Nineteen digit-tips were severed in Tamai zone I and 10 in Tamai zone II. The severed digit-tips were 7 of thumbs, 9 of index fingers, 5 of middle fingers, 5 of ring fingers and 3 of little fingers. Causes of injury were 12 of cut, 8 of crush and 6 of avulsion. Postoperative management included infection prevention, antispasmodic for 3 days and keeping in bed for 5 days. The time of surgery was recorded on all patients. Postoperative follow-ups were conducted at outpatient clinics for 6 to 12 months to observe the survival of digit-tips and the appearance, recovery of sensation and motor functions, strength of digits and patient satisfaction.Results:(1)The surgical time was about 1.0 hour for replantation of a severed digit-tip in Tamai zone I, while it took about 1.5 hours for those in Tamai zone II. (2)Survival rate and appearance: all 29 replanted digit-tips survived, except 2 in Tamai zone I which encountered venous occlusion and survived after small incision for bloodletting. Twenty-two digit-tips gained pulp fat pads with full digit pulps. Four avulsed digit-tips had mild atrophy of pulp. The 15 digit-tips severed in Tamai zone I were about 2 mm shorter than the healthy sides, but without deformity. One digit-tip had poor nail appearance due to preoperative fungal infection of nail bed. (3)Sensory recovery: with the British Medical Research Council (BMRC), 23 digit-tips recovered to S 3+, and 2 digit-tips of avulsion and 1 digit-tip of crush recovered to S 3. TPD of the replanted digit-tips were: 4-7 mm in those of cut injury; 6-8 mm in those of crush and 9-11 mm in those of avulsion. (4)Motion and digit strength: results of functional assessment according to the total active mobility standard promoted by China's Society for Surgery of the Hand were: 21 cases of excellent and 5 of good, without pain in digit pulp when pinching and griping. The mobility of the digits with replanted digit-tips of both Tamai zones I and II were close to that of the healthy sides. The motions of the digits with replanted digit-tips in Tamai zone I were close to the healthy sides and the 5 of those in Tamai zone II had 0° in extension and 2°-3° in flexion, due to the severed plane at distal interphalangeal joint. (5)Patient satisfaction: 25 patients were satisfied, however 1 patient was dissatisfied to the poor function of the distal interphalangeal joint due to the severed thumb-tip in Tamai zone II. Conclusion:Modified replantation procedure for severed digit-tip in Tamai zones I-II has significant achievement in cutting down the surgical time through a modified procedure of debridement and fracture fixation (tendon suture) by naked-eyes operation first, followed by dissections and anastomoses of the blood vessels and nerves under the surgical microscope. The auxiliary small incision by the lateral nail fold of digit-tip in Tamai zone I facilitates an exposure of a constant, healthy lateral nail fold vein. It enables the anastomosis with a high-quality vein, hence improves the success rate of replantation. The appearance and function of the replanted digit-tip are found better in the severed digit-tips of cut injury than those with injuries of avulsion and crush.