Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective To predict the target of Atractylodes-Panxia-Poria in the treatment of pancreatic cancer, and to explore its potential molecular mechanism by using network pharmacology and molecular docking. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), PharmMapper, OMIM, GeneCards, STRING, DAVID and Cytoscape software were used to construct a series of network diagrams. The core targets and conduct GO analysis and KEGG pathway enrichment analyses of the target genes were selected. Finally, molecular docking verification of key active ingredients and potential targets were conducted by AutoDock software. Results A total of 35 active ingredients, 190 related targets, 1566 targets of pancreatic cancer and 76 intersection targets were screened for the treatment of pancreatic cancer with Atractylodes-Panxia-Poria. These intersection targets were mainly involved in several biological processes, including positive regulation of gene expression, cytokine-mediated signaling pathway and regulation of apoptotic process, etc, which were also related to pathways in cancer, hepatitis B, colorectal cancer, chemical carcinogenesis-receptor activation, pancreatic cancer, and MAPK signaling pathway, etc. Molecular docking results showed that the main active components of Atractylodes-Panxia-Poria had certain affinity with the potential targets of pancreatic cancer. Conclusion Atractylodes-Panxia-Poria mainly exerts a therapeutic effect on pancreatic cancer through multi-component, multi-target and multi-pathway, which provides a certain theoretical basis for the clinical application of Atractylodes -Panxia-Poria in the treatment of pancreatic cancer.

Objective To assess the efficacy and side effects of intravesical instillation of BCG after transurethral resection of the bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients.Methods The clinical data of patients treated with BCG 120 mg per course induced perfusion or more after TURBT from December 2013 to October 2016 in 18 hospitals of northeast China region,were analyzed retrospectively.The first part,data of 106 patients with moderate,high-risk NMIBC were collected.A total of 83 patients were male,while the other 23 patients were female.The average age was 66.7 years old.The clinical staging were T1 in 86(81.1％) cases,Ta in 20(18.9％) cases and carcinoma in situ in 6 (5.7％) patients.Intravesical instillation of BCG was executed after transurethral resection of the bladder tumor.The incidence rate of recurrence and progression during more than 6 months' follow-up time were observed.Multivariate analyses were done by using logistic analysis and Cox proportional hazards regression model with Kaplan-Meier method.The second part,treatment compliance of 276 patients with bladder cancer,including moderate/high-risk NMIBC in 263 cases,moderate/high-risk NMIBC followed with renal pelvis/ureteral carcinoma in 8 cases were and moderate/high-risk NMIBC with renal pelvis/ureteral carcinoma in 5 cases who treated with BCG after the surgeries,were observed.Patients consisted of 211 males and 65 females with average age of 68.3 years.Results With a median follow-up of 12 months,9 (8.5％) patients experienced tumor recurrence and 2 (1.9％) patients were found progression in the first part.The one-year cancer free recurrence rate of the patients was 91.5％.Statistically significant prognostic factors for recurrence identified by multivariable analyses were prior recurrence of the tumors (OR =3.214,95％CI0.804-12.845,P =0.099).In the second port,an incidence rate of adverse effects was 64.1％ (177/276).The Ⅲ/Ⅳ degree complications were occurred in 11 patients and satisfactory outcomes achieved with active treatment.A total of 36 patients withdrawal with the major causes were recurrence and progression of bladder tumor in 12 cases (4.4 ％),9 cases (3.3 ％) with economic reasons and 11 cases (4.0％) with serious complications.Conclusions NMIBC patients treated with intravesical BCG therapy have approving cancer free recurrence rates and acceptable adverse effects.Prior recurrence may be prognostic factor of recurrence after intravesical BCG therapy.

AIM:To investigate the effect of MK-2206, an inhibitor of protein kinase B (Akt), on the DNA damage of SGC-7901 cells.METHODS: SGC-7901 cells were treated with different concentrations of MK-2206, and phosphorylated histone H2AX (γ-H2AX) foci formation was detected by immunofluorescence staining .Western blot analy-sis was used to exam the levels of DNA damage-related protein.The expression of LC3-Ⅱ was determined to evaluate the change of autophagy .RESULTS:MK-2206 treatment increased the formation of γ-H2AX foci and histone H2AX phospho-rylation in the SGC-7901 cells.The levels of DNA damage response protein were also increased .In addition, MK-2206-treated SGC-7901 cells increased the expression of LC 3-II, a hallmark of autophagy .Inhibition of autophagy significantly enhanced MK-2206-mediated histone H2AX phosphorylation.CONCLUSION:MK-2206 induces DNA damage and auto-phagy in SGC-7901 cells.Blocking autophagy potentiates the response of MK-2206-induced DNA damage .

BACKGROUNDOveractive bladder (OAB) is a series of symptoms with high prevalence in elderly people. This study was conducted using the overactive bladder symptom score (OABSS) to evaluate the efficacy of solifenacin succinate for the treatment of OAB.

METHODSThis was a prospective, multicenter, single-arm, 12-week study that enrolled 241 OAB patients. The patients received 5-10 mg/day solifenacin. Changes in OABSS, symptoms from voiding diary, perception of bladder condition (PPBC) score, international prostate symptom score (IPSS) and quality of life (QOL) were evaluated at weeks 0, 4, and 12. The relationship between OABSS and PPBC score or parameters of voiding diary was also evaluated.

RESULTSAt baseline, the mean OABSS for all patients was 9.41 ± 2.40, and was reduced significantly at week 12 (-3.76 points; 61.21%, P < 0.0001). The OABSS subscore, PPBC score, IPSS, and QOL were also significantly reduced during the study (P < 0.0001). The overall incidence of adverse events was 19.91% (44 cases). The gastrointestinal system was the most commonly affected (11.31%). Around 5.88% of the cases had adverse events related to the genitourinary system. There was a strong correlation between OABSS and urinary symptoms that was recorded in the 3-day voiding dairy.

CONCLUSIONSWe showed that solifenacin was clinically effective for relieving OAB symptoms, considering the balance between efficacy, patients' well-being, and tolerability. OABSS integrates four OAB symptoms into a single score and can be a useful tool for research and clinical practice.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Muscarinic Antagonists ; therapeutic use ; Prospective Studies ; Quality of Life ; Quinuclidines ; therapeutic use ; Solifenacin Succinate ; Tetrahydroisoquinolines ; therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive ; drug therapy

Objective To summarize the treatment experience of the solitary kidney with renal artery aneurysm.Methods Clinical data of 1 solitary renal artery aneurysm patient treated in our hospital in May.2012 was retrospectively analyzed.The 48 yrs man with a history of hypertension for 10 years,but responded to medical treatment poorly.The highest blood pressure was up to 180/100 mmHg (1 mmHg =0.133 kPa).Preoperative check found that the serum creatinine was 64 μmol/L.Color Doppler ultrasound showed no detection of left kidney,the renal artery enlarged to the range of 21 mm× 14 mm.CT scan showed that the right renal artery locally enlarged,suggesting artery aneurysm.Renal computerized tomography angiography showed that left renal agenesis,right renal with artery aneurysm close to the renal hilum with size of 17.1 mm× 19.1 mm,was located on the distal renal artery bifurcation,involving 2 artery branches.The diagnosis was right solitary kidney with renal artery aneurysm.Renal aneurysm clip occlusion was performed under general anesthesia,blood pressure was controlled to 70/40 mmHg during the procedure.After exposing the renal artery,the renal artery was visible with a diameter of 25 mm and with a basement width about 19 mm,which located in the main renal artery and overrode the branches of the two renal arteries.After the clamp of the artery aneurysm from two sides to center and the middle part of it was overlapped,the artery aneurysm reduced obviously,and clipped the aneurysmal wall with noose suture.When loosen the clamp of main renal artery,the artery aneurysm was not enlarged,blood pressure up to 120/80 mmHg.Results The operation was successful,operation time was 75 min,intraoperative blocking time was 15 min,intraoperative blood loss was 50 ml,and there was no intraoperative and postoperative complication.Postoperatively immediate and the first postoperative day serum creatinine were 95 μmol/L and 150 μmol/L.2 week after surgery the index decreased to 74 μmol/L.After operation the blood pressure was control successful,and kept at 130/80 mmHg.Conclusions Solitary kidney with renal artery aneurysm is rare.Renal aneurysm clip occlusion is a safe,effective and feasible treatment option,especially for the patients with solitary kidney.

OBJECTIVETo investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM).

METHODSTwo hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics.

RESULTSThe comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (χ(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (χ(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (χ(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (χ(2) = 4.08, P < 0.05).

CONCLUSIONSDM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; complications ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Incidence ; Kidney Neoplasms ; complications ; Male ; Middle Aged ; Prognosis

Objective To evaluate the long-term therapeutic results and the safety of nephronsparing surgery(NSS) for the treatment of renal cell carcinoma. Methods Clinical data of 243 NSSfor renal cell carcinoma were retrospectively analysed. Of them, 159 were males and 84 were femaleswith average age of 58 years (range from 24 ?77 years). The average tumor size was 3. 4 cm (rangefrom 1.1 to 6. 7 cm). Three cases were solitary renal cell carcinoma, 11 were bilateral renal cell carcinoma; 237 cases were in stage T_(1a). and 6 cases were in stage T_(1b). No lymph node and distant metastasis, no renal vein cancer tumor embolus and inferior vena cava tumor embolus was found. Postoperative follow-up was carried out by ultrasound, CT and renal function. Cancer specific survival was estimated using Kaplan-Meier method and log-rank test. Results After a mean 31 months (1-147months) follow-up, long-term follow-up data were obtained in 232 cases because the other 11 did notlive in Dalian, 52 were treated with interferon. Four of the 232 patients treated with NSS had died:1died from lung cancer 16 months after lung cancer treatment, the other 3 died from cardiovascular diseases. The total survival rate and cancer specific survival rate were 98. 3% and 100. 0%, respectively.Local tumor recurrences were detected in 5 patients and tumor metastasis was detected in 1 patient.The recurrence rate was 2. 2%, and the metastasis rate was 0. 4%. The complications included temporary renal failure and urine leakage. The complication rate was 5. 6%. Conclusions NSS for renalcell carcinoma is a safe and feasible treatment option. It has the advantages of low local recurrence,good long-term survival rate and low complication rate. NSS can maximally reserve functional nephron, reduce the risk of chronic renal failure, preserve patient's quality of life and increase patient'ssatisfaction.

Objective To study the relationship between X-linked inhibitor of apoptosis protein (XIAP) expression and transitional cell carcinoma(TCC) development. Methods Forty-three TCC tissues and 12 normal transitional epithelial tissues were applied to detect XIAP expression by semi-quantitative RT-PCR, immunohistochemistry and western blot. The data were statistically analyzed by using SPSS11.5 according to the 2 groups (TCC and normal transitional epithelial) as well as the dif-ferent subgroups (tumor stage, grade, single or multiple tumor, primary or recurrence tumor). Results XIAP expression in TCC tissues was higher than in normal transitional epithelial tissues(im-munohistochemistry: 22±5 and 16±2, Western blot:1.21±0. 15 and 0. 61±0.24, mRNA: 1.17± 0. 30 and 0. 75±0. 17, P<0. 05). In the bladder tumors group, XIAP expression in recurrence tumors was higher than in primary tumors(immunohistochemistry: 24±3 and 20±3, Western blot: 1.66±0.28 and 1.10±0. 23, mRNA: 1.44±0. 27 and 1.05±0. 23, P<0. 05). However, there were no significant differences according to the tumor stage and tumor grade as well as tumor multi-plicity or not. Conclusion XIAP expression might serve as a biomarker in TCC diagnosis and recur-rence prediction.

Objective To investigate the clinical characteristics of postinfectious irritable bowel syndrome (PI-IBS) in Qingdao. Methods Two hundred and four PI-IBS and 2068 non-PI-IBS patients were investigated with questionnaire including general information, symptoms and quality of life scores with microecological study before and after therapy. Results (1) The morbidity rate of PI-IBS in female was 2. times of that in male, which was similar to that in non-PI-IBS. (2) Brainwork labors dominated in both PI-IBS and non-Pl-lBS patients. (3) As to the simultaneous presence of extra-gastrointestinal symptoms,there was no statistical difference between the rate of physical symptoms in PI-IBS and non-PI-IBS patients (X<'2>= 10. 5, P>0.05) ,but the rate of mental symptoms was higher in PI-IBS than in non-PI-IBS patients, and the difference was significant(X<'2>= 28.7, P<0.05). (4)The alteration of intestinal microflora rate in PI-IBS was obviously higher than that in non-PI-IBS patients. (5) The quality of life scores in PI-IBS was improved after treatment with Birid Triple Viable , and there was significant difference(t =3. 8, P<0.01),but there was no statistical difference in non-Pl-IBS (t = 1.5, P>0.05). Conclusion There was some difference in certain clinical characteristics between PI-IBS and non-PI-IBS patients in Qingdao.