Objective To observe the effects of metformin on expression of Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK),nuclear factor-κB (NF-κB) and transforming growth factor β1 (TGF-β1) in cultured rat glomerular mesangial cells (MCs),and explore its renoprotective mechanisms.Methods MCs were cultured in the medium with normal glucose (group NG,5.6 mmol/L),high glucose (group HG,25mmol/L) and different concentrations of metformin (group M1,M2,M3).After 48 h exposure,the supernatants and MCs were collected.The expression of NF-κB and TGF-β1 mRNA was analyzed by real time-PCR.Total-AMPK,phospho-Thr-172 AMPK (p-AMPK),NF -κB p65 and TGF-β1 were visualized by Western blot.Results The real time-PCR and Western blot result showed MCs could express AMPK,NF-κB and TGF-β1 mRNA and protein.After stimulated by HG,the levels of intracellular NF-κB and TGF-β1 expressions were significantly increased compared with group NG (P ＜ 0.05); The levels of NF-κB and TGF-β1 were significantly decreased in group M1,M2 and group M3 compared with group HG in a dose-dependent manner.After stimulated by HG,the level of intracellular p-AMPK were down-regulated compared with group NG(all P ＜ 0.05); The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend (P ＜ 0.05),while the level of total-AMPK protein was unchanged with exposure to HG or different concentrations of mefformin(P ＞ 0.05).Conclusion Metformin can suppress the expression of NF-κB and TGF-β1 of glomerular MCs induced by HG via AMPK activation,which may partly contribute to its reno-protection.

Objective To investigate the method of the resectoscope combined with ureteroscope in seeking for the difficult ureteral orifice in glandular cystitis, which improved the success rate of double J stent insertion under endoscopy.Methods The clinical data of 8 patients with dififcult ureteral oriifce in glandular cystitis from March 2015 to May 2016 were retrospectively analyzed. All male patients, their age ranged from 38 to 64 years old, the average age was 44.3 years. The depth of the submucosa and muscle layer of the bladder lesion was treated by transurethral resection. The necrotic tissue of ureteral oriifce was excised, which revealed the changing of muscular layer of texture. Then, resected the muscle tissue, urine was seen through the thin layer of muscle tissue. Under the guidance of the guide wire was inserted, the ureteroscope observation was confirmed ureteral lumen and the double J stent was placed.Results All patients were successfully placed double J stent. The mean operation time was 83.2 min (range, 35.0~205.0 min). Intraoperative blood loss was range 20~50 ml. The catheter was removed in 3~5 d. The abdominal plain iflm was reviewed in 1 - 2 days and the position of the double J stent was good, there was no ectopic, distortion and so on. There was no complications occurred during the perioperative period.Conclusions Resectoscope combine with ureteroscope in seeking for the dififcult ureteral oriifce in glandular cystitis is an effective way of increasing the successful rate of ifnding dififcult ureteral oriifce. This method is safe,minimally invasive and avoiding open surgery.

Objective To evaluate the impact of aderent perirenal fat (APF) on retroperitoneal laparoscopic partial nephrectomy (RLPN). Methods Clinical data of 52 patients who underwent RLPN for a small renal tumor from October 2013 to December 2015 was analyzed retrospectively. All the patients were divided into two groups according to the presence of APF by preoperative computed tomography imaging. Clinical data was collected including patients' age, gender, BMI, history of hypertension, history of diabetes, American Society of Anesthesiologists score (ASA), intra-abdominal fat (IAF), tumor size, RENAL Nephrometry score (RNS), operative time, warm ischaemia time (WIT), estimated blood loss (EBL), and length of hospital stay. Results Between the two groups, the BMI, tumor size, WIT, length of hospital stay were similar [(26.70 ± 3.33) kg/m2 vs (25.65 ± 4.01) kg/m2, (3.53 ± 1.21) cm vs (3.64 ± 1.05) cm, (27.17 ± 7.55) min vs (25.21 ± 5.64) min, (12.54 ± 4.06) d vs (10.61 ± 3.70) d, P > 0.05)], as well as the ASA and RNS. APF patients were older [(59.25 ± 11.03) y vs (49.71 ± 11.86) y, P = 0.004]. There were a high proportion of men (75.0% vs 46.4%, P = 0.036), patients with hypertension (62.5% vs 28.6%, P = 0.014), and patients with diabetes (41.7% vs 14.3%, P = 0.026). In the APF group, IAF was more [(2.02 ± 0.47) cm vs (1.35 ± 0.66) cm, P = 0.000], operative time was longer [(146.08 ± 45.45) min vs (119.32 ± 28.83) min, P = 0.017], and EBL was higher [(82.92 ± 45.73) ml vs (51.79 ± 25.10) ml, P = 0.005]. Conclusion The adherent preirenal fat sticking renal results in a longer operative time and a higher EBL, but has no influences on the WIT and length of hospital stay. APF makes it difficult to expose the tumor, not to remove it.

Objective To explore the correlation between the variability of blood potassium level and risk of renal insufficiency(RI)in elderly heart failure(HF)patients with chronic systolic dys-function.Methods A total of 157 consecutive elderly patients with chronic HF admitted in De-partment of Cardiovascular Medicine of Wuhu First People's Hospital from January 2020 to No-vember 2022 were included,and according to whether RI occurred or not,they were divided into the RI group(36 cases)and the non-RI group(121 cases).Their general data and blood potassium variability was collected and recorded,and all of them were followed up for 6 months.Multivariate logistic regression analysis was applied for the correlation between blood potassium variability and RI in the elderly patients with chronic HF.Results The range of change,maximum fluctuation rate and coefficient of variation for blood potassium were significantly higher in the RI group than the non-RI group(P＜0.01).Multivariate logistic regression analysis showed that length of hospi-tal stay(OR=1.174,95％CI:1.067-1.292,P=0.001),age(OR=1.939,95％CI:1.309-2.872,P=0.001),albumin level(OR=0.866,95％CI:0.751-0.997,P=0.046),and range of change(OR=1.774,95％CI:1.519-2.071,P=0.016),maximum fluctuation rate(OR=1.631,95％CI:1.265-2.167,P=0.001)and coefficient of variation of blood potassium(OR=1.670,95％CI:1.212-2.230,P=0.002)were independent influencing factor for RI in the patients.Logistic re-gression analysis indicated that the range of serum potassium change≥0.80,the maximum fluctu-ation rate ≥0.40,and the coefficient of variation of serum potassium ≥8.20 were closely correla-ted with RI in elderly patients with chronic HF(P＜0.01).Conclusion High variability of blood potassium level is a risk factor for RI in elderly patients with chronic HF.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Objective To compare the clinical efficacy of peritoneolaparoscopic single position nephreteral total length resection(PSPNTLR)and posterior laparoscopic subabdominal incision technique(PLSIT)in the treatment of upper urothelial carcinoma(UTUC).Methods A total of 82 UTUC patients treated in our hospital during Jan.2018 and Feb.2021 were divided into the observation group(n=41,treated with PSPNTLR)and control group(n=41,treated with PLSIT)according to the random number table method.Perioperative indicators,pain degree,inflammatory factors,bladder recurrence and distant metastasis were compared between the two groups.Results The operation time[(122.15±15.14)min vs.(160.88±17.26)min],hospitalization time[(10.07±2.14)d vs.(12.22±3.13)d]and postoperative exhaust time[(1.46±0.57)d vs.(3.10±0.88)d]were significantly shorter,the intraoperative blood loss[(42.85±4.88)mL vs.(78.22±8.17)mL]and drainage volume[(53.61±9.74)mL vs.(81.56±11.06)mL]were significantly less in the observation group than in the control group(P＜0.05).The visual analogue score(VAS)of the observation group at 6,12 and 24 h after operation was significantly lower than that of the control group(P＜0.05).The levels of interleukin-6(IL-6)and C-reactive protein(CRP)were increased in both groups one day after surgery,but the indexes were increased more significantly in the control group(P＜0.05).During the 2-year follow-up after surgery,there were no statistical difference in bladder recurrence(12.20％vs.14.63％)and distant metastasis(9.76％vs.4.88％)between the two groups(P＞0.05).Conclusion Both PSPNTLR and PLSIT have good therapeutic safety,but PSPNTLR is more effective in improving perioperative indicators,reducing postoperative pain,and inhibiting inflammatory factors.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

BACKGROUNDThe renoprotective mechanisms of adenosine monophosphate (AMP)-activated protein kinase (AMPK) agonist - metformin have not been stated clearly. We hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines. The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta 1 (TGF-β1) induced by high glucose (HG) in cultured rat glomerular mesangial cells (MCs).

METHODSMCs were cultured in the medium with normal concentration glucose (group NG, 5.6 mmol/L), high concentration glucose (group HG, 25 mmol/L) and different concentrations of metformin (group M1, M2, M3). After 48-hour exposure, the supernatants and MCs were collected. The expression of NF-κB, MCP-1, ICAM-1, and TGF-β1 mRNA was analyzed by real time polymerase chain reaction. Western blotting was used to detect the expression of AMPK, phospho-Thr-172 AMPK (p-AMPK), NF-κB p65, MCP-1, ICAM-1, and TGF-β1 protein.

RESULTSAfter stimulated by HG, the expression of NF-κB, MCP-1, ICAM-1, TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG (P < 0.05). Both genes and protein expression of NF-κB, MCP-1, ICAM-1, TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner (P < 0.05). The expression of p-AMPK increased with the rising of metformin concentration, presenting the opposite trend, while the level of total-AMPK protein was unchanged with exposure to HG or metformin. Conlusion Metformin can suppress the expression of NF-κB, MCP-1, ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation, which may partly contribute to its reno-protection.

AMP-Activated Protein Kinases ; metabolism ; Animals ; Cells, Cultured ; Glomerular Mesangium ; cytology ; Glucose ; pharmacology ; Mesangial Cells ; drug effects ; metabolism ; Metformin ; pharmacology ; NF-kappa B ; metabolism ; Rats