Objective To investigate the expression of DNA methyltransferase 1 (DNMT1)mRNA in tissue of human transitional cell carcinoma of bladder(TCCB)and its clinical significance.Methods DNMT1 mRNA expression in 35 tumor tissues and 10 normal bladder tissues was measured by real-time PCR.Results Higher expression of DNMT1 transcripts was detected in tumor(3.25±0.74)than in normal tissues(1.53±0.44,P＜0.001).The expression level of DNMT1 mRNA in stage Tis-T1,T2-T4 was 3.14±0.67,3.31±0.84;in grade Ⅰ,Ⅱ,Ⅲ was 3.13±0.59,3.25±0.64,3.43±0.55;in patients older tham 40 years and younger than 40 years was 3.34±0.50.3.01±0.27;in male and female group was 3.31±0.42,3.01±0.20;in primary and recurrence group was 3.21±0.63,3.45±0.33.mRNA levels did not correlate with grade.stage and recurrence (P＞0.05).Higher levels of expression were associated with advanced age(P＜0.05).Male group had significant higher levels of expression than female group(P＜0.05).Conclusions Over-expres-sion of DNMT1 may play an important role in TCCB.DNMT1 can be an important therapeutic target in TCCB.

@@

Objective: To determine the correlation of IgM deposition with clinic-pathological features and outcomes of IgA nephropathy patients. Methods: A total of 1060 patients, who were diagnosed as IgA nephropathy by renal biopsies between 2001 and 2007 in Guangxing Hospital were enrolled. According to immunofluorescent test, patients were divided into patients with mesangial IgM deposition and patients without IgM deposition. Renal survival curves were assessed by Kaplan-Meier method. The effect of IgM deposition on outcomes of IgA nephropathy patients was examined by univariate and multivariable Cox proportional-hazards regression. Results: Among 1060 IgA nephropathy patients, there were 750 patients with IgM deposition and 310 patients without IgM deposition. (1) Urinary protein and uric acid in patients with IgM deposition were significantly higher than those in patients without IgM deposition (all P<0.05). Other clinical indicators shown no statistical difference (all P>0.05). Moreover, IgM deposition patients had higher serum IgA, serum IgG and serum IgM (all P<0.05). (2) In pathological indicators, IgM deposition patients had more segmented sclerosis or adhesions (S1 of Oxford classification), activity lesions as inflammatory cell infiltration and mesangial proliferation, and chronic pathological changes as tubular atrophy, segmented glomerular damage than patients without IgM deposition (all P<0.05). (3) All patients were followed-up for a median of 89.7(61.8, 113.4) months, Kaplan-Meier analysis revealed that kidney survival rate was significantly lower in IgM deposition patients compared with patients without IgM deposition (Log-rank χ²=4.95, P=0.026). In a univariate Cox hazards regression mode, IgM deposition was a risk factor for poor prognosis of IgA nephropathy patients (HR=1.597, 95% CI 1.053-2.422, P=0.027). However, in a multivariable Cox analysis, IgM deposition shown no influence on outcomes of IgA nephropathy patients (HR=1.409, 95% CI 0.921-2.156, P=0.114). Conclusions IgA nephropathy patients with IgM deposition have higher urinary protein, and more serious pathological damage and immune fluorescence deposition. IgM deposition affects renal survival of IgA nephropathy, while IgM deposition is not an independent risk factor for prognosis of IgA nephropathy.

Objective To evaluate the feasibility and safety of 180W greenlight laser in the treatment of benign prostatic hyperplasia (BPH) in the day surgery mode.Methods A retrospective review included 65 patients with benign prostate hyperplasia who were treated with photoselective vaporization of the prostate (PVP) under 180W greenlight system from Jan 2017 to Jan 2018,was performed.The patients' age ranged from 54 to 75 years old and the prostatic volume ranged from 42 to 93 ml.All patients were classified into two groups [day sugery group (n =29) and inpatient surgery group(n =36)] based on the wishes of patients.In day sugery group,the admission,operation and discharge were completed in 24 hours.The preoperative clinic parameters such as prostate volume,IPSS,Qmax QOL and PVR were recorded in the two groups.The prostatic volume in two groups was (67.3 ± 15.9) ml and (70.4 ± 16.1) ml,respectively.The IPSS and QOL scores in two groups were (23.2±4.6 vs.23.9±4.5) and (4.7±0.9 vs.4.4± 0.8),respectively.The Q and PVR in two groups were [(6.7 ± 2.5) ml/s vs.(6.8 ± 2.8) ml/s] and [(133.9 ± 81.3) ml vs.(105.8 ± 76.3) ml],respectively.The time of catheterization and postoperative hospitalization,total cost,postoperative adverse events were recorded,too.All the clinic data of preoperation,intraoperation and postoperation were compared between two groups.Results The operations and follow-up were successfully executed in all patients.There were not statistical significance differences in preoperative parameters between the two groups (P ＞ 0.05).There were not statistical significance differences in operating time [(67.8 ± 9.8) min vs.(70.9 ± 12.8) min],laser time [(49.8 ± 8.3) min vs.(51.6±10.4) min],energy used [(295.7±112.6) kJ vs.(285.0±108.2) kJ],between the two groups,too (P ＞ 0.05).A significantly less mean catheter duration,hospital stay and hospital charges were observed in the day surgery group [(14.6 ±2.0)hours,(0.5 ±0) days and (23 279 ±511) yuan,respectively] than in the inpatient surgery group [(51.7 ± 1 1.8) hours,(3.0 ± 0.8) days and (27 452 ± 440)yuan,respectively,P ＜0.05].3 cases of urinary retention and 1 case of gross hematuria after the catheter removal were recorded in the day surgery group,2 cases of urinary retention were recorded in the inpatient surgery group,and all of these 6 cases were cured through indwelling catheter.After 3 months follow up,there were not statistical significant differences io IPSS(12.4 ± 3.3 vs.10.6 ± 4.2),Q [(17.4±2.1)ml/s vs.(17.1 ±1.8) ml/s],and QOL (2.1 ±0.7 vs.2.3±0.7)between the two groups (P ＞ 0.05).However,significant difference of those items could be noticed when compared with those items before surgery (P ＜ 0.05).Conclusions In the day surgery mode,180W greenlight laser vaporization of the prostate is safe and effective,without the increase of surgical complications.The length of stay and hospitalization expenses were much less.Thus,this strategy is worth promoting in clinical practice.

Objective:To evaluate the relationship between dyslipidemia and uric acid urolithiasis, and explore the risk factors of uric acid urolithiasis.Methods:93 patients with uric acid urolithiasis identified by stone composition analysis were retrospective analyzed from January 2014 to October 2019 were classified as uric acid urolithiasis group.Among them there were 77 men accounting for 82.8%, 16 women accounting for 17.2%, the median age is 64 years old.According to sex, age and other conditions, 321 patients with calcium oxalate urolithiasis in the same period were selected as calcium oxalate stone group. Among them there were 264 men accounting for 82.2%, 57 women accounting for 17.8%, the average age is 64 years old.While 306 non-stone people examined in hospital as control group in the same period who matched with age and gender. Among them there were 252 men accounting for 82.4%, 54 women accounting for 17.6%, the average age is 61 years old. There was no significant difference in age and sex ratio among the three groups. The body mass index (BMI) of uric acid urolithiasis group, calcium oxalate urolithiasis group and control group were significantly different( P<0.01). Serum uric acid, urine pH and blood lipids: triglyceride (TG), cholesterol (TC), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C) were recorded in the three groups, and the correlation between the above indexes and stone composition was analyzed.The uric acid urolithiasis group was divided into hyperuricemia(HUA) group (n=41) and Non HUA group (n=52) according to serum uric acid, and 66 cases with HUA were selected in the control group. The dyslipidemia and urine pH levels of the above three groups were compared. The multivariate Logistic regression analysis was used to identify the independent risk factors associated with uric acid urolithiasis formation. Results:There were significant differences in TG level, incidence of hypertrigly-ceridemia, low HDL-cholesterolemia, high LDL-cholesterolemia, serum uric acid and urine pH between uric acid urolithiasis group and calcium oxalate urolithiasis group( P<0.05). Significant differences were seen in TG level, HDL-C level, incidence of hypertriglyceridemia and low HDL-cholesterolemia, serum uric acid and urine pH between uric acid urolithiasis group and control group.There was significant difference in urine pH between uric acid urolithiasis with and Non HUA group. Significant difference in the incidence of hypertriglyceridemia and low HDL-cholesterolemia were seen between uric acid urolithiasis with HUA group and HUA group.Multivariate Logistic regression analysis showed that obesity(odds ratio=1.68, P<0.001), hypertriglyceridemia(odds ratio=7.37, P=0.002), low HDL-cholesterolemia(odds ratio=10.46, P=0.001) and low urinary pH(odds ratio=0.10, P<0.001) were independent risk factors for uric acid urolithiasis. Conclusions:Dyslipidemia was more likely associated with uric acid urolithiasis. Obesity, hypertriglyceridemia, low HDL-cholesterolemia and low urinary pH are closely related to the occurrence of uric acid urolithiasis.

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

ObjectiveTo study the efficacy of community rehabilitation combined with drug therapy on rehabilitation of patients with schizophrenia in rural communities， and to provide references for community rehabilitation of patients with schizophrenia in rural areas of our country. MethodA total of 81 patients in rural communities of three towns in Lanzhou new area who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） were randomly divided into study group （n=39） and control group （n=42）. Both groups received general drug treatment. On this basis， the study group received community rehabilitation intervention for 6 months. Before and after intervention， Positive and Negative Syndrome Scale （PANSS）， Activity of Daily Living Scale （ADL）， Social Disability Screening Schedule （SDSS） and Schizophrenia Quality of Life Scale （SQLS） were used to assess the psychotic symptoms， social function and quality of life in two groups. ResultsAfter intervention， the PANSS total score ［（55.54±14.75） vs. （63.52±13.95）， t=-2.504， P=0.014］， negative symptom factor score ［（15.64±4.50） vs. （18.38±5.13）， t=-2.547， P=0.013］ and general psychopathological factor score ［（25.67±7.39） vs. （30.35±6.60）， t=-3.015， P=0.003］ of the study group were lower than those of the control group. The SDSS score ［（8.21±3.78） vs. （10.21±4.67）， t=-2.118， P=0.037］ and SQLS score ［（18.97±6.23） vs. （22.43±8.04）， t=2.150， P=0.035］ of the study group were lower than those of the control group. ConclusionCommunity rehabilitation combined with drug therapy may help alleviate psychotic symptoms， improve social function and improve quality of life in patients with schizophrenia in rural communities.

Objective:To investigate the effects of hyperuricemia on the prognosis of IgA nephropathy (IgAN) using propensity score matching (PSM) method.Methods:IgAN patients proven by biopsy were included. PSM was used to match patients. Kaplan-Meier method was used for survival analysis, and Cox regression analysis was used to analyze the effects of hyperuricemia on IgAN prognosis. Primary outcome events were defined as death, or end-stage renal disease (dialysis, transplantation), or a decrease in estimated glomerular filtration rate (eGFR) greater than 40%. Renal outcome was defined as end-stage renal disease (dialysis, transplantation), or a decrease in eGFR greater than 40%.Results:A total of 1 454 IgAN patients were included in this study, including 850 females and 604 males. Uric acid level was (368.26±92.87) μmol/L in the males, and (277.23±92.71) μmol/L in the females. The median follow-up time was 85.00(56.10, 106.33) months. During the follow-up period, a total of 134 patients reached the primary outcome events, including 5 deaths, 24 dialysis patients, 5 kidney transplant patients, and 100 patients with eGFR decreased by more than 40%. After 1∶1 matching, 131 males and 159 females in the hyperuricemia group were successfully matched with 131 males and 159 females in the normal uric acid group, and there was no significant statistical difference in each parameter in baseline between the hyperuricemia group and normal uric acid group after matching. Kaplan-Meier survival analysis showed that either before or after matching, the incidence of primary outcome events in male or female patients with hyperuricemia was higher than those with normal uric acid, but there was no statistically significant difference in incidence of primary outcome events between female hyperuricemia group and female normal uric acid group after matching (Log-rank test, χ2=3.586, P=0.058). Cox proportional hazard regression model showed that, in the pre-match fully adjusted model, the hazard ratio ( HR) of entering primary outcome events was 2.29-fold (95% CI 1.27-4.11, P=0.006) for men with hyperuricemia and 1.85-fold (95% CI 1.01-3.37, P=0.045) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering primary outcome events was 2.41-fold (95% CI 1.18-4.93, P=0.016) for men with hyperuricemia and 1.83-fold (95% CI 0.91-3.67, P=0.091) for women with hyperuricemia compared with those with normal uric acid. In the pre-match fully adjusted model, the HR of entering renal outcome events was 2.68-fold (95% CI 1.47-4.88, P=0.001) for men with hyperuricemia and 1.81-fold (95% CI 0.99-3.33, P=0.056) for women with hyperuricemia compared with those with normal uric acid. In the post-match fully adjusted model, the HR of entering renal outcome events was 2.89-fold (95% CI 1.36-6.15, P=0.006) for men with hyperuricemia and 1.81-fold (95% CI 0.88-3.72, P=0.106) for women with hyperuricemia compared with those with normal uric acid. Conclusion:Hyperuricemia may be associated with IgAN progression, and it has a more significant effect on male IgAN patients.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.