Objective To investigate the influence of fasudil on the epithelialmesenchymal transdifferentiation of renal tubular epithelial cells in diabetic rats and to explore the mechanism. Methods Wistar mts were randomly divided into three groups:control,diabetes and fasudil-treatment.All the rots were sacrificed after three months of feeding with or without fasudil.Pathological changes of the glomeruli and renal interstitium were studied by periodic acidSchiff'S staining and Masson staining,respectively.Expression of ROCKI,α-SMA,E-cadherin and the distribution of β-catenin was examined by immunohistochemistry.Changes in the MYPT1 phosphorylation profile and α-SMA,E-cadherin and membrane β-catenin expression were detected bv Western blot.Changes in the levels of ROCKI,E-cadherin and total β-eatenin mRNA expression were analyzed by real-time PCR. Results Fasudil treatment notably attenuated renal interstitial fibrosis in diabetic rats.Compared to the control rats.diabetic rats showed an elevated phosphorylation of MYFF1(P<0.01),increased expression of α-SMA(P<0.01),decreased expression of E-cadherin and membrane β-catenin(P<0.01,respectively)and increased expression of ROCKI,total β-catenin mRNA(P<0.01,respectively),decreased expression of E-cadherin mRNA(P<0.01 ). Fasudil treatment for diabetic rats attenuated MYPT1 phosphorylation (P<0.01), decreased α-SMA expression (P<0.01), increased E-cadherin and membrane (β-catenin expression (P<0.01, respectively), and reduced ROCKI, total β-catenin mRNA expression (P <0.01, respectively), increased expression of E-cadherin mRNA (P<0.01). Conclusions Fasudil may reduce the epithelial-mesenchymal transdifferentiation and renal interstitial fibrosis in diabetic rats through the inhibition of ROCK activity. Such effect further facilitates the recovery of the cell-cell adhesion among renal tubular epithelial cells and the formation of adhesion complex.

Objective To investigate whether erythropoietin (EPO) can inhibit the proapoptotic effect of high glucose on rat proximal tubular epithelial cells, and the possible mechanisms in which EPO exerts its anti-apoptotic role. Methods Rat proximal tubular epithelial cells (NRK-52E) were divided into 5 groups: normal control group, osmolarity control group, high glucose group, high glucose with EPO (50 U/ml) group and high glucose with EPO (100 U/ml) group. The expression of EPO receptor (EPOR) in NRK-52E cells was examined by immunocytochemistry. The effect of high glucose on the expression of EPOR was detected by Western blotting. The rate of apoptosis was evaluated by flow cytometry Annexin V-FITC/PI double stains. The intracellular ROS was detected using fluorescent probe CM-H2DCFDA. The expression of bcl-2, bax and caspase-3 mRNA were examined by RT-PCR. Results The expression of EPOR was demonstrated in NRK-52E cells, and high glucose could up-regulate the expression of EPOR. High glucose could induce oxidative stress in NRK-52E cells, and up-regulate the mRNA expression of bax and caspase-3, down-regulate the mRNA expression of bcl-2. These effects of high glucose on NRK-52E cells could be reversed by EPO. Conclusion EPO inhibits NRK-52E cells apoptosis induced by high glucose through attenuating oxidative stress,up-regulating theexpression of bcl-2 mRNA and down-regulating the expression of bax and caspase-3 mRNA, which may be mediated by EPOR.

Objective To investigate the renoprotective effect of erythropoietin(EPO) in streptozotocin-induced diabetic rats and to explore the possible mechanism.Methods The SD rats were randomly divided into there groups: normal control rats, diabetic, diabetic treated with EPO(NC, DM, DE groups).The rats were sacrificed after 8 weeks treatment.Renal morphology was observed by light microscopy.The expression of erythropoietin receptor(EPOR) in kidney was detected by immunofluorescence and Western blotting.The expression of p47phox, transforming growthfactor (TGF)β1andfibronectin (FN)proteininkidneywasdetectedby immunohistochemistry and Western blotting.The activity of antioxidants including total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the level of malondialdehyde(MDA) in kidney were also measured.Results EPO treatment notably attenuated renal pathologic and functional changes.The expression of EPOR was found in kidney,but there was no difference among groups(P＞0.05).Compared with normal rats, diabetic rats showed an elevated expression of p47phox, TGF-β1, FN proteins and MDA levels in kidney as well as reduced activities of SOD, GSH-Px and T-AOC (all P＜0.01).Compared with diabetic rats, EPO could decrease the protein expression of p47phox,TGF-β1and FN in kidney (all P＜0.05).Meanwhile, elevated MDA level in the kidney was decreased as well as decreased SOD, GSH-Px,T-AOC activities were significantly remitted in DE group(all P＜0.01).Conclusion EPO can amelioraterenaldamagevia theinhibition of oxidativestressandTGF-β1andFNprotein expression in streptozotocin-induced diabetic rats.

Objective To explore the application effect of the adult education theory in the nursing round. Methods 340 trainee nurses, who were trained at our surgical department between June 2008 and December 2009, were randomly divided into the experimental group(178 cases)and the control group(162cases). The adult education theory was adopted in the experimental group, whereas the traditional education method was used in the control group, a questionnaire was carried out after the nursing visit. Results The experimental group was more satisfied with the round visit than the control group. Conclusions The application of the adult education theory in the round visit is beneficial not only to the students' selection of the topics of nursing visit, but also to the improvement of the students' understanding and communicating capacity, the students' studying interests and the students' creative thinking, finally the degree of satisfaction to the round visit is increased by the adoption of this theory.

Objective:To investigate the effect of interleukin (IL)-7 receptor α (IL-7Rα) antibody on the immune inflammation and renal injury in MRL/lpr lupus mice.Methods:Fifteen 3-4-week-old female MRL/lpr lupus mice (specific pathogen free) weighing 15-16 g were bred to 14-week-old and randomly divided into three groups: IL-7Rα antibody intervention group, isotype antibody (positive control) group and normal saline (negative control) group. The mice in the threc groups were intraperitoneally injected with IL-7Rα antibody, isotype antibody and normal saline respectively, with 100 μg three times a week for 4 weeks. At the age of 18-week old, the mice were sacrificed. Twenty-four-hour urinary protein was detected by Coomassie brilliant blue method, serum creatinine was detected by peroxidase method, and the expression of autoantibody (anti-double strand DNA antibody) and inflammatory factors such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-21 was detected by enzyme-linked immunosorbent assay method. Renal pathology was detected by PAS and Sirius red staining, and CD3 and F4/80 in renal tissues were detected by immunohistochemistry method. Regulatory T cells, follicullar helper T cells (Tfh) and follicular regulatory T cells (Tfr) were detected by flow cytometry.Results:The 24-hour urinary protein, serum creatinine, serum anti-double strand DNA antibody and serum IFN-γ and IL-21 in the IL-7Rα antibody intervention group were significantly lower than those in the control groups (all P<0.01). However, there was no significant difference in serum TNF-α among the three groups ( F=0.39, P>0.05). The positive infiltrating cells of CD3 and F4/F80, and the ratio of type Ⅰ/Ⅲ collagen fibers ( F=41.11, P<0.01) of renal tissues in the IL-7Rα antibody intervention group were lower than those in the other two groups. Compared with the control groups, the ratio of regulatory T cells (CD4 +CD25 +Foxp3 +)/effector T cells (CD4 +CD25 +) in blood of IL-7Rα antibody intervention group increased ( F=21.64, P<0.01), while the ratio of Tfr (CD4 +CXCR5 +Foxp3 +)/Tfh (CD4 +CXCR5 +) in peripheral blood and spleen increased ( F=38.95, P<0.01; F=12.90, P<0.01). Conclusion:IL-7Rα antibody can reduce the production of autoantibodies such as anti-double strand DNA antibody and inflammatory factors by increasing the ratio of regulatory T cells and Tfr/Tfh, thus alleviating immune inflammation and renal damage in MRL/lpr lupus mice.

Objective To evaluate the correlation between intracranial vertebral artery (VA) stenotic lesions at different locations and posterior circulation ischemia (PCI) symptoms.Methods The present study included 362 cases of patients with unilateral VA severe stenosis or occlusion confirmed by carotid Doppler ultrasonography,CT angiography and (or) digital subtraction angiography.According to the relationship between the location of stenotic lesion and posterior inferior cerebellar artery (PICA),all cases were divided into pre-PICA group (n=73) and post-PICA group (n=289).According to presentation of PCI symptoms,all cases were divided into symptomatic group (n=133) and asymptomatic group (n=229).On CDFI,hemodynamic parameters were analyzed and recorded,which included the peak systolic velocity (PSV),end diastolic velocity (EDV),resistance index (RI) and VA diameter (VAD) and spectrum shape.And the correlation between location of intracranial VA stenosis / occlusion and PCI symptoms was evaluated.The hemodynamic parameters of bilateral intervertebral segments were compared in patient with unilateral intracranial VA stenosis by paired t test.The ipsilateral intervertebral segment hemodynamic changes were compared among patents with different locations of unilateral intracranial VA stenosis by using independent sample t test.Using 2 × 2 crosstables and Pearson 22 test,the correlation between the location of VA stenosis and PCI symptoms was analyszed.Results Hemodynamic parameters of VA were associated with its stenotic location to PICA.The comparison of the ipsilateral and contralateral VA showed that PSV,EDV and RI,VAD had significant difference (43.97± 1.22 vs 55.82± 1.08,6.35±0.23 vs 19.41 ±0.48,0.850±0.004 vs 0.640± 0.005,2.75 ± 0.04 vs 4.00± 0.03),difference was statistically significan (t=-7.086,-23.754,-32.603,23.842,all P ＜ 0.001).The intervertebral segment PSV,EDV and RI of ipsilateral VA were significantly related to the stenotic location to PICA (t=-6.665,-17.459,22.143,P＜0.001),but not for VAD (P＞0.05).In pre-PICA group,the intervertebral segment spectrum of ipsilateral VA was unimodal-style,while in post-PICA group the spetrum was high-resistance-style.VA intracranial severe stenosis at different locations was not associated with the symptoms of PCI (r=0.023,P=0.782),while VA intracranial occlusion at different locations was associated with the symptoms of PCI significantly (r=0.792,P ＜ 0.05).Conclusions CDU is a non-invasive,real-time and dynamic assessment tool for VA intracranial lesions in different locations,which can provide reliable information for clinical treatment and prognosis prediction.

Objective:To investigate the nutritional risk, incidence of malnutrition, and intake of three major energy-supplying nutrients, analyze changes in their body composition and the possible influencing factors in patients with stomach neoplasms during perioperative period in order to provide a theoretical basis for the nutritional management of patients with stomach neoplasms during perioperative period.Methods:This was a cross-sectional study. A total of 105 patients who underwent gastric cancer radical surgery in the Gastrointestinal Department of Zhongshan Hospital Affiliated to Xiamen University from June 2021 to May 2023 were taken as the research subjects using fixed-point continuous sampling method. They were recruited for screening and assessment using Nutritional Risk Screening 2002 (NRS 2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Nutrients intake during the perioperative period were investigated using the 24-h recall method and dietary diary method, etc. Body compositions were measured using the bioelectrical resistance method.Results:Among the 105 patients, there were 78 males and 27 females, with an average age of (61.5 ± 10.3) years. About 83.8% (88/105) gastric cancer patients were at nutritional risk and 82.9% (87/105) were malnourished. The preoperative and postoperative energy intake were (1 646.1 ± 321.5) and (1 317.2 ± 365.8) kcal (1 kcal=4.184 kJ), respectively, which were significantly lower than the target amount of (1 896.7 ± 262.9) kcal, the difference was statistically significant ( t=6.23, 8.29, both P<0.05).The preoperative body mass, muscle mass, skeletal muscle, fat mass, and skeletal muscle index were (51.5 ± 9.6), (40.8 ± 6.0), (23.6 ± 4.0), (8.3 ± 4.9) kg, and 6.7 ± 0.8 respectively, while the postoperative values were (50.0 ± 9.1), (39.8 ± 6.0), (22.8 ± 3.6), (7.8 ± 5.2) kg, and 6.5 ± 0.8 respectively, with statistically significant differences between the two groups ( t values were 2.89-10.61, all P<0.05). Logistic multivariate regression analysis showed that the operation time ( OR=3.984, 95% CI 1.433-11.080, P<0.05) and energy satisfaction ( OR=0.053, 95% CI 0.005-0.610, P<0.05) were independent influencing factors for the degree of skeletal muscle loss. Conclusions:During perioperative period, the gastric cancer patients had poor nutritional status with insufficient nutrient intake and accelerated loss of body muscle and fat. Therefore, it was necessary to conduct a comprehensive nutritional evaluation for patients with stomach neoplasms during perioperative period in time and take steps to promote recovery by providing individualized nutritional therapy.

Objective To develop a model for predicting cryptogenic stroke(CS)in patients with right to left shunt(RLS)through the patent foramen ovale(PFO).Methods We consecutively included 66 patients with CS confirmed by cranial magnetic resonance imaging and PFO-related RLS verified by contrast-enhanced transcranial Doppler ultrasonogra-phy and transesophageal echocardiography who were admitted to the Department of Neurology of The First Affiliated Hospi-tal of Soochow University from January 2020 to October 2022.83 patients diagnosed with PFO-RLS without stroke during the same period were included in the non-stroke(NCI)group.We analyzed the clinical data,anatomical parameters of PFO,and PFO-RLS status of patients;explored factors affecting the risk of CS in patients with PFO-RLS through a multi-variable logistic regression analysis;and built a combined prediction model,and evaluated its performance using the area under the receiver operating characteristic curve(AUC)in comparison with those of individual indicators with the use of the Delong test.Results At baseline,the CS group had significantly higher systolic and diastolic blood pressure levels and D-dimer levels as well as significantly greater PFO diameter and length than the control group(all P<0.05).The mul-tivariable logistic regression analysis revealed that hypertension,higher D-dimer levels,larger PFO diameter,and longer PFO length were factors affecting the risk of CS in patients with PFO-RLS,with the odds ratios[95%confidence intervals(CI)]being 4.16(1.31-13.15),1.01(1.00-1.01),2.29(1.14-4.61),and 1.19(1.03-1.36),respectively(all P<0.05).The AUCs(95%CI)of the combined prediction model,hypertension,D-dimer,PFO diameter,and PFO length were 0.79(0.71-0.86),0.64(0.55-0.73),0.62(0.53-0.71),0.67(0.58-0.75),and 0.65(0.56-0.74),respectively.According to the Delong test,the AUC of the combined prediction model differed sig-nificantly from those of individual indices(all P<0.05).At the optimal cut-off value,the sensitivity and specificity of the combined prediction model were 0.73 and 0.76,respectively.Conclusion Hyperten-sion,increased D-dimer levels,larger PFO diameter,and longer PFO length were factors associated with CS in patients with PFO-RLS.The combined prediction model is effec-tive in predicting the risk of CS for patients with PFO-RLS.

Objective To explore the dynamic changes in cerebral hemodynamics in patients with unilateral middle cerebral artery(MCA)occlusion after superficial temporal artery(STA)-MCA bypass surgery.Methods One hundred and nine patients diagnosed with unilateral MCA occlusion by DSA who underwent STA-MCA bypass surgery were retrospectively included in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University.Clinical data of patients were collected within 24 hours after admission,including age,sex,body mass index,stroke risk factors including hypertension,hyperlipidemia,diabetes,smoking,drinking history and atrial fibrillation,clinical manifestations(within the last 6 months;nonspecific symptoms[dizziness,memory loss,unresponsiveness,etc.],transient ischemic attack,and stroke),blood biochemical markers(low density lipoprotein cholesterol,high density lipoprotein cholesterol,triglyceride,total cholesterol,fasting blood glucose,and hypersensitive C-reactive protein),and National Institutes of Health stroke scale(NIHSS)score at admission.Color Doppler ultrasound(CDU)and transcranial color coded Doppler(TCCD)ultrasound were used to evaluate the hemodynamic parameters of STA before and at different periods after surgery(4-7 days and 1,3,6,12 months after surgery)to analyze the patency of bypass arteries and intracranial hemodynamic changes,and to check the consistency of the results of the bridge artery patency at 12 months postoperatively by CDU and DSA,consistency test was performed.According to the results of the DSA examination 12months after surgery,the patients were divided into the bypass artery patency group and the non-patency group(stenosis or occlusion).The hemodynamic parameters at the trunk of STA,namely the extracranial segment,transcranial,and intracranial part of the bypass arteries,were compared between the two groups.It included inner diameter(D),peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),pulsation index(PI),time-averaged mean velocity(TAMV),time-averaged peak velocity(TAPV),and calculated flow of the STA trunk including TAMV flow and TAPV flow.Head CT,CT angiography(CTA)above the aortic arch,and CT perfusion(CTP)of the whole brain were performed 1 to 3 days before surgery and 12 and 18 months after surgery to observe the changes in cerebral perfusion.Head CT was performed 1 to 2 days after the operation to observe whether there were new hemorrhagic and ischemic lesions in the operative area.the CTP parameters of the two groups were compared including 12 and 18 months after the operation with 1 to 3 days before the surgery,and the differences in CTP parameters between the two groups were compared.The modified Rankin scale(mRS)was used to evaluate the neurological function prognosis of the patients at 12 and 18 months after surgery.The mRS score 2 was divided into a good prognosis and mRS score≥3 was a poor prognosis.NIHSS score of the patients was recorded 7 days,12,and 18 months after surgery.Results(1)Consistency analysis of CDU and DSA:the consistency of the assessment of bypass artery patency was excellent at 12 months after surgery,and the Kappa value was 0.94(95％CI 0.81-1.00,P＜0.01).According to DSA,101 cases(92.7％)were in bypass artery patency group,while 8 cases(7.3％)in the non-patency group(no case of occluded bridge vessel was found),and the sites of stenosis in the bypass arteries were all located in the transcranial segment.(2)Hemodynamic parameters:compared with the preoperative results,the D of the extracranial segment increased on 4-7 days and 1,3,6,and 12 months after the operation(Wald x2=30.438).Hemodynamic parameters included increased blood velocity such as PSV,EDV,TAMV,and TAPV(Waldx2 was 12.117,29.310,31.075 and 17.525,respectively)and blood flow including TAMV flow and TAPV flow(Wald x2 was 54.503 and 34.986,respectively)increased,while RI and PI values were decreased(Waldx2 was 112.568 and 103.629,respectively),and the differences were statistically significant(all P＜0.05).However,there was no significant difference in hemodynamic parameters in the non-patency group at 12 months after operation(all P＞0.05).Compared with 4-7 days after surgery,PSV(252.0[206.8,315.3]cm/s vs.102.5[84.0,119.0]cm/s)and EDV(119.5[106.3,159.8]cm/s vs.43.5[36.8,52.0]cm/s)in the non-patency group were significantly higher at the cranial entrance 12 months after surgery(both P＜0.05),but there was no significant difference in RI and PI values(both P＞0.05).Compared with 4-7 days after surgery,the blood flow parameters of STA intracranial segment,including PSV(29.4[24.8,41.4]cm/s vs.111.5[63.3,120.0]cm/s),EDV(19.7[15.2,22.2]cm/s vs.58.5[28.3,70.0]cm/s)and PI(0.55[0.42,0.63]vs.0.83[0.61,0.90])values in the non-patency group at 12 months after surgery were significantly decreased(all P＜0.05).(3)CTP parameters:the relative cerebral blood flow(rCBF)of the patency group increased at 12 and 18 months after surgery compared to preoperative levels,while relative cerebral blood volume(rCBV),relative peak time(rTTP)and relative mean transit time(rMTT)decreased,with statistical significance(all P＜0.05).At 12 and 18 months after operation,rCBF increased,while rMTT decreased in the non-patency group(both P＜0.05),but there was no significant difference as for rCBV and rTTP.The rTTP of the patency group at 12 and 1 8 months was lower than that of the non-patency group(12 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.024;1 8 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.023),but there was no statistical significance for other parameters between the two groups(all P＞0.05).(4)NIHSS score and prognosis:clinical follow-up results 18 months after the operation showed that no new stroke occurred during the follow-up period.The NIHSS scores in the patency group and the non-patency group were remarkably lower at 7 days,12,and 18 months after surgery than at admission(patency group:2[0,4],1[0,2],0[0,2]vs.3[0,6],respectively;the non-patency group:3[1,5],3[1,6],2[1,6]vs.4[1,7],respectively),with significant differences(all P＜0.05);However,the NIHSS scores in the patency group were significantly lower than that in the non-patency group at 12 and 18 months after surgery,and the proportion of patients with good prognosis in the patency group was substantially higher than that in the non-patency group(12months:87.1％[88/101]vs.4/8,P=0.039;18 months:90.1％[91/101]vs.4/8,P=0.025).Conclusion CDU can quantitatively evaluate the hemodynamic changes of bypass arteries after the STA-MCA bypass procedure,which can be applied to the long-term dynamic follow-up after the surgery.

Objective:To assess the efficacy and safety of cinepazide maleate injection in the treatment of patients with acute ischemic stroke.Methods:A multicenter, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial, led by Peking Union Medical College Hospital, was conducted in 65 Hospitals in China. The efficacy of cinepazide maleate injection in patients with acute anterior circulation cerebral infarction with onset time of ≤48 hours, 7≤National Institute of Health stroke scale (NIHSS) score ≤25 was assessed from August 2016 to February 2019, using the proportion of modified Rankin scale (mRS) score≤1 and Barthel index (BI) score≤95 on day 14 as efficacy endpoint. The patients were divided into treatment group who were treated with cinepazide maleate injection and control group who were treated with placebo.Results:A total 937 patients were involved in the final efficacy analysis (466 in treatment group and 471 in control group). The proportion of subjects with mRS score≤1 on day 14 after treatment were higher in the treatment group than that in the control group (102/466(21.89%) vs76/471(16.14%)). Logistic regression analysis showed that patients treated with cinepazide maleate were significantly more likely to have a favorable outcome (mRS score≤1) than patients treated with placebo on day 14 ( OR=0.677, 95% CI 0.484-0.948 , P=0.023), and patients treated with cinepazide maleate were more likely to reach independence in activities of daily living (Barthel Index ≥95) than those treated with placebo on day 14 (125/466(26.82%) vs 91/471(19.32%); OR=0.632, 95% CI0.459-0.869, P=0.005). The rate of adverse events was similar between the treatment and control groups. Conclusion:The 14-day treatment with cinepazide maleate injection could reduce the degree of disability whereas did not increase the risk of adverse events.