Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To investigate the correlation between basilar artery (BA) dolichosis and clinical outcome of patients with acute isolated pontine infarction.Methods:Consecutive patients with acute isolated pontine infarction within 7 d after onset admitted to the Department of Neurology, the Affiliated Hefei Hospital of Anhui Medical University were enrolled. The demographic, clinical and MRI data were collected. The modified Rankin Scale was used to evaluate the clinical outcome at 3 months after the onset. 0-2 was defined as good outcome, and >2 was defined as poor outcome. A binary multivariate logistic regression model was used to analyze the correlation between BA dolichosis and clinical outcome of the patients. Results:A total of 116 patients with acute isolated pontine infarction were enrolled. There were 69 (59.5%) males and 47 (40.5%) females, with a median age of 65 years (interquartile range: 57-76 years). There were 39 patients (33.6%) in BA dolichosis group and 77 (66.4%) in non-BA dolichosis group. The BA diameter ( P=0.021), theoretical length (basilar artery length, BAL) ( P<0.001), bending length (BL) ( P<0.001) and the proportion of patients with BA bending ( P<0.001) in the BA dolichosis group were significantly higher than those of the non-BA dolichosis group. There were 93 (80.2%) patients in good outcome group and 23 (19.8%) in poor outcome group. The baseline National Institute of Health stroke scale (NIHSS) score ( P<0.001), approximate length of BA ( P=0.007), BAL ( P=0.020), BL ( P=0.005) and the proportion of patients with BA dolichosis ( P=0.002) and bending ( P=0.008) in the poor outcome group were significantly higher than those in the good outcome group. Spearman correlation analysis showed that the approximate length of BA was significantly positively correlated with BL ( r=0.597, P<0001). Multivariate logistic regression analysis showed that BA dolichosis (odds ratio 5.441, 95% confidence interval 1.814-16.320; P=0.003) and the higher baseline NIHSS score (odds ratio 1.696, 95% confidence interval 1.291-2.228; P<0.001) were the independent risk factors for poor outcomes in patients with acute isolated pontine infarction. Conclusion:BA dolichosis is common in patients with acute isolated pontine infarction. BA dolichosis may be an independent risk factor for poor outcome in patients with acute isolated pontine infarction at 3 months after onset.

Aim To observe the effect of total flavonoid from Mori folium(TFMF) on renal interstitial fibrosis in type 1 diabetic mice and its possible mechanism.Methods Diabetic mice were induced by intraperitoneal injection of streptozotocin(STZ) dissolved in 0.01 mol·L-1 citrate buffer(pH 4.5) at 150 mg·kg-1 body weight after 12 h of food deprivation.Forty model mice were divided randomly into four groups: model group, and low-(0.25 g·kg-1), moderate-(0.5 g·kg-1), high-dose groups(1 g·kg-1) fed with TFMF once daily.In addition, eight normal mice were used as normal group.After 12 weeks, the fasting blood glucose(FBG), serum creatinine(Cr), blood urea nitrogen(BUN) and microalbuminuria(mAlb) were measured.Masson staining, Sirius red staining and collagen type Ⅳ immunohistochemical staining were used to detect the expression of collagen protein in the cortex, while laminin staining to assess the degree of glomerular and renal tubular basement membrane thickening.The protein expressions related to epithelial-mesenchymal transition and PI3K/Akt/mTOR in the renal cortex of mice were detected by Western blot.Results The moderate and high dose of TFMF could significantly decrease the levels of FBG, Cr, BUN and mAlb in diabetic mice, meanwhile decreasing the expression of α-SMA protein by inhibiting the activation of PI3K/Akt/mTOR signaling pathway, which led to the amelioration of the pathological alterations of renal tissue.Conclusions The moderate and high dose of TFMF can reduce the level of renal interstitial fibrosis in type 1 diabetic mice, and its mechanism may be related to the inhibition of activation of PI3K/Akt/mTOR signaling pathway.

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7–36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7–36) (10, 20, 40 µg/kg i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7–36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7–36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7–36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.
Animals ; Blood Glucose ; Brain ; Diet, High-Fat ; Hypoglycemic Agents ; Infarction ; Infarction, Middle Cerebral Artery ; Malondialdehyde ; Neurons ; Neuroprotective Agents ; Phosphotransferases ; Rats* ; Reperfusion ; Reperfusion Injury* ; Streptozocin ; Superoxide Dismutase

ObjectiveTo investigate the effect and safety of endoscopic injection of cyanoacrylate in the treatment of esophageal and gastric variceal bleeding (EGVB) in children. MethodsThe clinical data of 35 children with acute EGVB who were treated with endoscopic injection of cyanoacrylate in Children′s Hospital of Baoji Maternal and Child Health Care Hospital from August 2010 to August 2015 were analyzed retrospectively. The emergency response rate, rebleeding rate, and incidence of complications after the treatment were analyzed statistically. ResultsThirty-five patients received 46 times of endoscopic injection of cyanoacrylate in total. The response rate to the initial injection was 95.6% (44/46). The volume of cyanoacrylate injected was 0.2-0.6 ml, with a mean volume of 0.4±0.2 ml. The emergency hemostasis rate was 93.4% (43/46), the rebleeding rate was 11.4% (4/35), and the cycle for 4 patients with the recurrence of bleeding to be cured was 1.2-23.0 months (mean 121±10.9 months). One patient experienced abdominal pain, and no patients experienced ectopic embolism. Two patients died after injection. ConclusionFrequent, small-volume endoscopic injection of cyanoacrylate is an effective and convenient therapeutic method for EGVB in children, has few complications, and holds promise for clinical application.

Objective To compared the efficacy of hyaluronan combined with eperisone hy-drochloride or simple application of hyaluronan or eperisone hydrochloride in the treatment of pa-tients with knee osteoarthritis (OA).Methods 99 patients with knee OA were randomly divided into hyaluronan group,eperisone hydrochloride group and combined group (hyaluronan combined with eperisone hydrochloride),33 cases in each group.Efficacy was compared among 3 groups. Rsults 5 weeks after treatment,WOMAC score of combined group was significantly higher than hyaluronan group and eperisone hydrochloride group.The CTX-Ⅱ content of urine in combined group was significantly lower than the other two groups (P <0.05).Conclusion Combination of hyaluronan and eperisone hydrochloride can significantly improve the clinical symptoms of patients with knee OA,and its efficacy is obviously better than simple application of hyaluronan or eperisone hydrochloride.

Objective To investigate the influence of comprehensive nursing intervention in elderly diabetic patients with acute cerebral infarction .Methods 84 elderly cerebral infarction patients were randomly divided into observation group (n =42)and control group (n =42),the control group was gave conventional nursing method,and the observation group was given the comprehensive nursing intervention.Symptoms of the patients was improved and healthy levels were observed.Results The overall effective rate of the observation group was much higher than the control group,the difference in the overall effective rate of two groups was statistically signifi-cant (P <0.05).The NIHSS score of observation group after nursing was significantly lower than in the control group,the difference was statistically significant(P <0.05).The ADL score of ob-servation group after nursing was significantly higher than the in the control group,the result re-vealed that the difference was statistically significant (P <0.05).Conclusion The systematic nursing intervention can help to improve the prognosis of patients with cerebral infarction and the life quality.

Objective To compared the efficacy of hyaluronan combined with eperisone hy-drochloride or simple application of hyaluronan or eperisone hydrochloride in the treatment of pa-tients with knee osteoarthritis (OA).Methods 99 patients with knee OA were randomly divided into hyaluronan group,eperisone hydrochloride group and combined group (hyaluronan combined with eperisone hydrochloride),33 cases in each group.Efficacy was compared among 3 groups. Rsults 5 weeks after treatment,WOMAC score of combined group was significantly higher than hyaluronan group and eperisone hydrochloride group.The CTX-Ⅱ content of urine in combined group was significantly lower than the other two groups (P <0.05).Conclusion Combination of hyaluronan and eperisone hydrochloride can significantly improve the clinical symptoms of patients with knee OA,and its efficacy is obviously better than simple application of hyaluronan or eperisone hydrochloride.