Objective:To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods:This prospective, multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria: Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC), recurrent acute episodes of urinary tract infection(rUTI), and non-febrile complicated urinary tract infection(cUTI) with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine. Exclusion criteria: ①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h. ②Fever (>37.3℃) or symptoms of upper urinary tract infection such as low back pain, tapping pain in the kidney area, etc. ③Indwelling urinary catheter. At the first visit, clean midstream urine samples were taken for bacterial culture, and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed. Extended spectrum β-lactamases (ESBLs) were measured for Gram-negative bacteria. The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method. Drug resistance rate, sensitivity rate were analyzed between different disease groups.Results:There were 404 enrolled patients from 9 hospitals, including 364 (90.1%) females and 40 (9.9%) males. A total of 177 strains of pathogenic bacteria were isolated, among which the highest proportion of Escherichia coli was 66.1% (117/177).Klebsiella pneumoniae was followed by 6.8% (12/177) and Streptococcus agalactis 5.1% (9/177). The bacterial spectrum distribution of AUC and rUTI were similar, and the proportions of Escherichia coli were 70.6% (85/119) and 65.9% (29/44), respectively. However, the proportions of Escherichia coli isolated from cUTI patients were only 28.6% (4/14) and Enterococcus faecalis 7.1%(1/14). The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139). The sensitivity rate of nenoxacin was 74.6%(91/122), and the resistance rate was 25.4%(31/122). The overall sensitivity rate of levofloxacin was 44.9%(70/156) and the resistance rate was 36.5%(57/156). The rate of resistance of urinary tract pathogens to levofloxacin was 48.2% (27/56) in patients with previous urinary tract infection history, and 30.0% (30/100) in patients with no previous urinary tract infection history, the difference was statistically significant( P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7% (65/92) and that to levofloxacin was 50.0% (46/92, P<0.001). The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0% (16/20), and that to levofloxacin was 70.0% (14/20, P=0.009). Conclusions:The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases. The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI. The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin. The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.

Objective:To investigate the clinical efficacy and safety of Pseudomonas aeruginosa injection in preventing reurrent urinary tract infection in women. Methods:This was a multicenter, randomized, open, positive-controlled, non-inferiority trial involving female patients with recurrent urinary tract infections (rUTIs) who were admitted to 11 medical centers in China. Inclusion criteria: ①Aged 18-70 years, with verifiable clinical data showing at least 3 episodes of acute UTIs within 1 year and at least 2 episodes within 6 months, and cured by antimicrobial therapy; ② At the time of enrollment, the patients had no obvious symptoms of urinary tract irritation, normal white blood cell count in midstream urine routine (within the normal range of laboratory standards of each unit) or ≤3HP by centrifuge microscopy, negative leucocyte esterase and nitrite, and negative urine culture; ③No abnormal urinary anatomic function (such as urinary obstruction, calculus or congenital urinary malformation) and residual urine volume ≤50 ml were detected by B-ultrasound of urinary system; ④Informed consent signed by the person or agent; ⑤Clear consciousness, able to answer questions independently, according to the requirements of the test plan to complete the research questionnaire. Exclusion criteria: ①Patients allergic to the above drugs; ②Any complex signs of urinary tract infection or pyelonephritis (manifested as low back pain, fever ≥37.3℃, systemic symptoms); ③Drugs affecting immune function were used within 7 days before randomization; ④Patients with basic diseases of urinary system such as obstruction, calculus, urinary stenosis, vesicoureteral reflux or other functional abnormalities, urine diversion, indwelling catheter or stent tube or intermittent catheterization; ⑤Combined with or existing systemic lupus erythematosus, AIDS and other diseases that can lead to systemic immune function abnormalities; ⑥Patients who are known or suspected to be pregnant, breastfeeding, or planning a pregnancy within 3 months of stopping the drug; ⑦Patients with malignant tumors and mental patients; ⑧Persons who have received any other investigational drug treatment or participated in another interventional clinical trial within 4 weeks prior to screening; ⑨Failure to comply with the trial protocol or other conditions deemed unsuitable for enrollment by the investigator. Patients were randomly divided into 2 groups. The experimental group was given Pseudomonas aeruginosa injection for 5 times, 0.5 ml for the first time, and 1 ml/ time per week for the following 4 weeks. The control group was given fosfomycin aminotriol 3g orally, once every 10 days, for 9 consecutive times. The patients were followed up for 6 to 8 months, during which urinary tract symptoms developed and routine urine tests showed abnormally elevated white blood cells, which was defined as recurrent UTIs. Urine routine, liver and kidney function, and urinary secretory immunoglobulin A(SIgA) were reviewed 0-2 days (V2) after the 5th administration of the experimental group and the 4th administration of the control group. Urine routine and urine SIgA were reviewed at (90±10) d (V3) and (180±10) d (V4) after treatment. At (270±10) d (V5) after treatment, the recurrence (re-infection caused by the same species of bacteria) or re-infection (re-infection caused by non-same species of bacteria) of the two groups were compared, and non-inferiority analysis was performed, and the non-inferiority threshold was set at 0.2. Results:From March 2021 to May 2022, a total of 152 rUTIs patients were enrolled in this study, including 80 patients in the experimental group, 71 patients in the intention-to-analysis set (ITT) and 66 patients in the protocol analysis set (PPS). In the control group, 72 cases met ITT in 69 cases and PPS in 67 cases. There were no significant differences in age, body mass index, marital status, duration of urinary tract infection, history of diabetes, history of previous major surgery, history of infection, and urinary SIgA between the two groups (all P>0.05). The recurrence rates of the experimental group and the control group at V5 time point were 44.78% (30/67) and 42.65% (29/68), respectively ( P=0.803) (ITT data set analysis results showed that the difference in recurrence rates between the two groups was 0.0213(95% CI-0.1460-0.1886, P=0.0048). PPS data set analysis showed that the difference of recurrence rate between the two groups was -0.0021(95%CI -0.1711-0.1670, P=0.0109), and the recurrence rate of the experimental group was not worse than that of the control group. At V2 time points, there were no significant differences in liver and kidney function indexes between test group and control group ( P>0.05). At V2 to V4 time points, urinary SIgA of test group and control group were 0.90 (0.37, 2.89) mg/L and 1.32 (0.34, 3.08) mg/L, 1.54 (0.44, 3.23) mg/L and 1.71 (0.27, 2.92) mg/L, 1.11 (0.65, 3.42) mg/L and 2.18 (0.43, 3.26) mg/L, there was no statistical significance ( P>0.05). The incidence of adverse events in the experimental group was 30.0% (24/80), including 14 cases of redness, pain and discomfort at the injection site, 5 cases of fever, 2 cases of allergic rash, and 1 case of urticaria, headache and constipation each. The incidence of adverse events in the control group was 5.6% (4/72), all of which were diarrhea, and the difference between the two groups was statistically significant ( P<0.01). No life-threatening serious adverse events occurred in both groups, and all adverse events were self-healing without additional intervention. Conclusions:Compared with fosfomycin aminotriol, Pseudomonas aeruginosa injection has the same clinical effect in preventing rUTI and has good safety.

Objective:To investigate the clinical efficacy and safety of Pseudomonas aeruginosa injection in preventing reurrent urinary tract infection in women. Methods:This was a multicenter, randomized, open, positive-controlled, non-inferiority trial involving female patients with recurrent urinary tract infections (rUTIs) who were admitted to 11 medical centers in China. Inclusion criteria: ①Aged 18-70 years, with verifiable clinical data showing at least 3 episodes of acute UTIs within 1 year and at least 2 episodes within 6 months, and cured by antimicrobial therapy; ② At the time of enrollment, the patients had no obvious symptoms of urinary tract irritation, normal white blood cell count in midstream urine routine (within the normal range of laboratory standards of each unit) or ≤3HP by centrifuge microscopy, negative leucocyte esterase and nitrite, and negative urine culture; ③No abnormal urinary anatomic function (such as urinary obstruction, calculus or congenital urinary malformation) and residual urine volume ≤50 ml were detected by B-ultrasound of urinary system; ④Informed consent signed by the person or agent; ⑤Clear consciousness, able to answer questions independently, according to the requirements of the test plan to complete the research questionnaire. Exclusion criteria: ①Patients allergic to the above drugs; ②Any complex signs of urinary tract infection or pyelonephritis (manifested as low back pain, fever ≥37.3℃, systemic symptoms); ③Drugs affecting immune function were used within 7 days before randomization; ④Patients with basic diseases of urinary system such as obstruction, calculus, urinary stenosis, vesicoureteral reflux or other functional abnormalities, urine diversion, indwelling catheter or stent tube or intermittent catheterization; ⑤Combined with or existing systemic lupus erythematosus, AIDS and other diseases that can lead to systemic immune function abnormalities; ⑥Patients who are known or suspected to be pregnant, breastfeeding, or planning a pregnancy within 3 months of stopping the drug; ⑦Patients with malignant tumors and mental patients; ⑧Persons who have received any other investigational drug treatment or participated in another interventional clinical trial within 4 weeks prior to screening; ⑨Failure to comply with the trial protocol or other conditions deemed unsuitable for enrollment by the investigator. Patients were randomly divided into 2 groups. The experimental group was given Pseudomonas aeruginosa injection for 5 times, 0.5 ml for the first time, and 1 ml/ time per week for the following 4 weeks. The control group was given fosfomycin aminotriol 3g orally, once every 10 days, for 9 consecutive times. The patients were followed up for 6 to 8 months, during which urinary tract symptoms developed and routine urine tests showed abnormally elevated white blood cells, which was defined as recurrent UTIs. Urine routine, liver and kidney function, and urinary secretory immunoglobulin A(SIgA) were reviewed 0-2 days (V2) after the 5th administration of the experimental group and the 4th administration of the control group. Urine routine and urine SIgA were reviewed at (90±10) d (V3) and (180±10) d (V4) after treatment. At (270±10) d (V5) after treatment, the recurrence (re-infection caused by the same species of bacteria) or re-infection (re-infection caused by non-same species of bacteria) of the two groups were compared, and non-inferiority analysis was performed, and the non-inferiority threshold was set at 0.2. Results:From March 2021 to May 2022, a total of 152 rUTIs patients were enrolled in this study, including 80 patients in the experimental group, 71 patients in the intention-to-analysis set (ITT) and 66 patients in the protocol analysis set (PPS). In the control group, 72 cases met ITT in 69 cases and PPS in 67 cases. There were no significant differences in age, body mass index, marital status, duration of urinary tract infection, history of diabetes, history of previous major surgery, history of infection, and urinary SIgA between the two groups (all P>0.05). The recurrence rates of the experimental group and the control group at V5 time point were 44.78% (30/67) and 42.65% (29/68), respectively ( P=0.803) (ITT data set analysis results showed that the difference in recurrence rates between the two groups was 0.0213(95% CI-0.1460-0.1886, P=0.0048). PPS data set analysis showed that the difference of recurrence rate between the two groups was -0.0021(95%CI -0.1711-0.1670, P=0.0109), and the recurrence rate of the experimental group was not worse than that of the control group. At V2 time points, there were no significant differences in liver and kidney function indexes between test group and control group ( P>0.05). At V2 to V4 time points, urinary SIgA of test group and control group were 0.90 (0.37, 2.89) mg/L and 1.32 (0.34, 3.08) mg/L, 1.54 (0.44, 3.23) mg/L and 1.71 (0.27, 2.92) mg/L, 1.11 (0.65, 3.42) mg/L and 2.18 (0.43, 3.26) mg/L, there was no statistical significance ( P>0.05). The incidence of adverse events in the experimental group was 30.0% (24/80), including 14 cases of redness, pain and discomfort at the injection site, 5 cases of fever, 2 cases of allergic rash, and 1 case of urticaria, headache and constipation each. The incidence of adverse events in the control group was 5.6% (4/72), all of which were diarrhea, and the difference between the two groups was statistically significant ( P<0.01). No life-threatening serious adverse events occurred in both groups, and all adverse events were self-healing without additional intervention. Conclusions:Compared with fosfomycin aminotriol, Pseudomonas aeruginosa injection has the same clinical effect in preventing rUTI and has good safety.

Objective To study the effect of Pioglitazone(PIO) on intimal hyperplasia after vein graft and its potential mechanism.Methods 32 male Sprague-Dawley rats were randomly divieded into two groups,one admisnistrated with PIO(3 mg· kg-1 · d-1) and the other with saline.A week later,the right common carotid arteries were reconstructed using homolateral external jugular veins in rats.The drugs treatment was continued after surgery for 2 or 4 weeks until grafted veins were harvested.The neointima thickness was measured by Computer image analysis software.To observe the activation of ERK1/2 pathway,the western blot were performed.In vitro,human great saphenous vein smooth muscle cells were co-cultured with PIO,and cells proliferation was detected by the CCK-8 assay.The TUNEL staining was performed to determine apoptosis.Results PIO treatment significantly attenuated intimal thickening compared with the the control group both at second [(8.56 ± 1.64) μm vs (25.44 ± 0.89) μm,P ＜ 0.01] and fourth week [(10.51 ± 1.47) μm vs (35.69 ± 1.07) μm,P ＜ 0.01)] after veins graft.Also PIO inhibited the ERK1/2 activation in grafted veins.In vitro,PIO significantly reduced PDGF-induced cells proliferation and increased cells apoptosis.Conclusion PIO effectively improved intimal hyperplasia in grafted veins perhaps associated with its ability to suppress vascular smooth muscle cells proliferation and enhance cell apoptosis,and might be related to the down regulation of ERK1/2 activity.

Objective To compare epididymis-sparing orchiectomy (group A) with traditional orchiectomy (group B ) in patients with advanced prostate cancer,and to evaluate which procedure is better.Methods A total of 60 cases of advanced prostate cancer patients were enrolled,with 30 cases in group A and 30 cases in group B.They were given oral anti-androgen from 1 day after castration.Serum level of testosterone and prostatic specific antigen (PSA) was detected before castration,and 1 week,1,3,6,9 and 12 months after castration.Patient satisfaction was also evaluated.Results On time point of 12 months after castration,the average level of serum testosterone was 0.2 nmol/L (95 ％ confidence interval,0.1 ～ 0.9 nmol/L) in group A and 0.3 nmol/L (95％ confidence interval,0.2 ～ 0.9 nmol/L) in group B (P ＞0.05 ) ; the average value of PSA was 0.22 ng/ml in group A and 0.27 ng/ml in group B (P ＞0.05 ) ; patient satisfaction rate was 96.7％ (29/30) in group A and 53.3％ (16/30) in group B.Conclusions No significant difference of testosterone level and PSA is found between the 2 groups.However,epididymis-sparing orchiectomy meets the psychological needs better because it helps to maintain the appearance of the scrotum through epididymis preservation and epididymoplasty.