Xiaomin Han

Experience in management of Fournier’s gangrene: A report of 24 cases

Fournier’s gangrene (FG) is an extremely aggressive and rapidly progressive polymicrobial soft tissue infection of the perineum, anal area or genitalial regions with a high mortality rate. The objectives of this study were to share our experience with the management of this serious infectious disease over the last 15 years. This retrospective study examined 24 patients diagnosed as having FG who were admitted to our hospital between March 1996 and December 2011. The gender, age, etiology, predisposing factors, laboratory findings, treatment modality, hospitalization time and spread of gangrene of the subjects were all recorded and analyzed. The results showed that the mean age of the patients was 48.33 years, the male-to-female ratio was 5:1 and the mortality rate was 20.8% (5/24). The most common predisposing factor was diabetes mellitus in 10 patients (41.6%), followed by alcohol abuse, obesity, neoplasms and immunosuppression. The most common etiology was peri-anal and peri-rectal abscesses (45.8%), followed by lesions of urogenital origin (33.3%) and cutaneous (8.3%) origin. No local pathologies could be identified in 3 (12.5%) patients. The most commonly isolated microorganisms were Escherichia coli (62.5%), followed by Enterococcus, Pseudomonas aeruginosa and Staphylococcus aureus. The median admission Fournier’s gangrene severity index (FGSI) score for survivors was 5.63±1.89 against 13.6±3.64 for non-survivors which was designed for predicting the disease severity in the series. Early diagnosis and immediate extensive surgical debridement were significant prognostic factors in the management of Fournier gangrene. Individualized reconstructive modalities for wound coverage were useful in that they repaired the tissue defect and improved the quality of life. We are led to conclude that Fournier’s gangrene is a severe condition with a high mortality. The Fournier’s gangrene severity index (FGSI) score at admission serves as a good predictor for the disease severity. Early diagnosis, surgical debridement and aggressive fluid therapy are significant prognostic factors in the management of Fournier gangrene. Individualized reconstructive surgery modalities for wound coverage are useful to correct the tissue defect and improve the quality of life.SummaryFournier’s gangrene (FG) is an extremely aggressive and rapidly progressive polymicrobial soft tissue infection of the perineum, anal area or genitalial regions with a high mortality rate. The objectives of this study were to share our experience with the management of this serious infectious disease over the last 15 years. This retrospective study examined 24 patients diagnosed as having FG who were admitted to our hospital between March 1996 and December 2011. The gender, age, etiology, predisposing factors, laboratory findings, treatment modality, hospitalization time and spread of gangrene of the subjects were all recorded and analyzed. The results showed that the mean age of the patients was 48.33 years, the male-to-female ratio was 5:1 and the mortality rate was 20.8% (5/24). The most common predisposing factor was diabetes mellitus in 10 patients (41.6%), followed by alcohol abuse, obesity, neoplasms and immunosuppression. The most common etiology was peri-anal and peri-rectal abscesses (45.8%), followed by lesions of urogenital origin (33.3%) and cutaneous (8.3%) origin. No local pathologies could be identified in 3 (12.5%) patients. The most commonly isolated microorganisms were Escherichia coli (62.5%), followed by Enterococcus, Pseudomonas aeruginosa and Staphylococcus aureus. The median admission Fournier’s gangrene severity index (FGSI) score for survivors was 5.63±1.89 against 13.6±3.64 for non-survivors which was designed for predicting the disease severity in the series. Early diagnosis and immediate extensive surgical debridement were significant prognostic factors in the management of Fournier gangrene. Individualized reconstructive modalities for wound coverage were useful in that they repaired the tissue defect and improved the quality of life. We are led to conclude that Fournier’s gangrene is a severe condition with a high mortality. The Fournier’s gangrene severity index (FGSI) score at admission serves as a good predictor for the disease severity. Early diagnosis, surgical debridement and aggressive fluid therapy are significant prognostic factors in the management of Fournier gangrene. Individualized reconstructive surgery modalities for wound coverage are useful to correct the tissue defect and improve the quality of life.

Musashi-2 promotes migration and invasion in bladder cancer via activation of the JAK2/STAT3 pathway.

Musashi-2 (Msi2) is considered to have a crucial role in regulating various key cellular functions. However, the clinical significance and biological role of Msi2 in bladder cancer remains unknown. We examined the expression of Msi2 in bladder cancer cell lines in 167 clinical samples and the biological role of Msi2 in bladder cancer cells. Western blotting was used to investigate the possible mechanism of Msi2-induced migration and invasion in bladder cancer. Msi2 was significantly upregulated in bladder cancer cells and tissues compared with normal bladder urothelial cells and tissues. Immunohistochemical analysis revealed high expression of Msi2 in 57 of 167 (34.1%) bladder cancer specimens. Statistical analysis showed a significant correlation of Msi2 expression with advanced clinical stage, lymph node metastasis, and poor prognosis. Overexpression and ablation of Msi2 promoted and inhibited, respectively, the migration and invasion of bladder cancer cells. Furthermore, we found that Msi2 activated the JAK2/STAT3 pathway and promoted expression of genes downstream of JAK2/STAT3 in bladder cancer. This study demonstrates that Msi2 can induce bladder cancer cell migration and invasion by activating the JAK2/STAT3 pathway, and that Msi2 may be a valuable prognostic biomarker for bladder cancer patients.

Intervention of Nicotine on MNU-Induced Bladder Cancer in Rats

SummaryThis study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.

Culture of motor neurons from newborn rat spinal cord

SummaryA protocol for the isolation, purification and culture of motor neurons from newborn rat spinal cord was described and the effect of glial cell line-derived neurotrophic factor (GDNF) on the growth of neurite of motor neurons was investigated in vitro. Spinal motor neurons (SMNs) were dissociated from ventral spinal cord of postnatal day 1 rats. The culture system for SMNs was established by density gradient centrifugation, differential adhesion, and use of serum-free defined media and addition of exogenous GDNF. After 72-h culture, the cells displayed the characteristic morphology of motor neurons, exhibited extensive neuritic processes and were positive for choline acetyltransferase (ChAT) expression. The neurite length of SMNs in GDNF groups was significantly longer than that in control group (P<0.05). This protocol can be adapted for various postnatal motor neurons studies.A protocol for the isolation, purification and culture of motor neurons from newborn rat spinal cord was described and the effect of glial cell line-derived neurotrophic factor (GDNF) on the growth of neurite of motor neurons was investigated in vitro. Spinal motor neurons (SMNs) were dissociated from ventral spinal cord of postnatal day 1 rats. The culture system for SMNs was established by density gradient centrifugation, differential adhesion, and use of serum-free defined media and addition of exogenous GDNF. After 72-h culture, the cells displayed the characteristic morphology of motor neurons, exhibited extensive neuritic processes and were positive for choline acetyltransferase (ChAT) expression. The neurite length of SMNs in GDNF groups was significantly longer than that in control group (P<0.05). This protocol can be adapted for various postnatal motor neurons studies.

HBO1 promotes cell proliferation in bladder cancer via activation of Wnt/β-catenin signaling.

Histone acetyltransferase binding to ORC1 (HBO1), a histone acetyltransferase, was recently identified as an oncoprotein; however, its role in bladder cancer remains unknown. In this study, we showed that HBO1 was highly expressed at both the mRNA and the protein levels in bladder cancer. HBO1 expression was associated with the clinical features of human bladder cancer, including tumor size (P = 0.018) and T (P = 0.007) classifications. Patients with higher HBO1 expression had shorter recurrence‐free survival time, whereas patients with lower HBO1 expression had better survival time. Moreover, we found that ectopic overexpression of HBO1 promoted, whereas HBO1 silencing inhibited tumor growth in bladder cancer cells both in vitro and in vivo. We further demonstrated that upregulation of HBO1 activated the Wnt/β‐catenin signaling pathway and led to nuclear localization of β‐catenin and upregulation of downstream targets of of Wnt/β‐catenin signaling. These findings suggest that HBO1 plays a key role in the progression of bladder cancer via the Wnt/β‐catenin pathway, and may serve as a potential therapeutic target for the treatment of bladder cancer.

Persistence of uropathogenic Escherichia Coli in the bladders of female patients with sterile urine after antibiotic therapies

This study aimed to provide evidence of persistent uropathogenic Escherichia coli (UPEC) in female patients with recurrent urinary tract infection (UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors (VFs) of UPEC were determined using polymerase chain reaction (PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities (IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies (18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.This study aimed to provide evidence of persistent uropathogenic Escherichia coli (UPEC) in female patients with recurrent urinary tract infection (UTI) after antibiotic therapy. We collected biopsies of the bladder, and clean-catch urine samples from 32 women who had episodes of recurrent UTI and were given antibiotic therapy. Urine samples and biopsies were analyzed by conventional bacteriological techniques. Phylogenetic group and 16 virulence factors (VFs) of UPEC were determined using polymerase chain reaction (PCR). The infection capability of UPEC was confirmed in a mouse model. Immunofluorescence and electron microscopy were used to detect intracellular bacterial communities (IBCs) in the mouse model. The results showed that all urine specimens were detected sterile. E. coli was found in 6 of 32 biopsies (18.75%), and was identified to be UPEC by PCR. Different VFs associated with the formation of IBCs were identified in all six UPEC isolates. Each UPEC isolate was capable of forming IBCs within the bladder epithelial cells of mice. In conclusion, UPEC with distinctive pathological traits and the capability of IBC formation was first found in the bladders of women after antibiotic therapy, suggesting that the IBC pathogenic pathway may occur in humans and it plays an important role in UTI recurrence.

Urodynamic characteristics of rats with detrusor instability

The purpose of the present study is to investigate urodynamic characteristics of rats with detrusor instability (DI) induced by different causes. Forty-eight adult female Sprague-Dawly rats were randomly divided into 4 groups: cyclophosphamide group, bladder outlet obstruction group, lipopolysaccharide group and control group. The BL-410 model bio-function experimental system was applied to monitor bladder pressure and a number of urodynamic parameters were recorded and calculated, including the frequency of detrusor instability, maximum voiding pressure (MVP), maximum cystometric capacity (MCC), intercontraction interval (ICI), voiding time (VT), postvoid residual (PVR) and bladder compliance (BC). The positive rates of DI in cyclophosphamide group, bladder outlet obstruction group and lipopolysaccharide group were 83.33%, 75.00% and 58.33%, respectively. And correspondingly the frequency of DI was 10.00±2.00, 4.87±1.24 and 3.50±1.00tmin(-1), which was significantly higher than those of the control group (P<0.05). Compared with the control group, the decrease of MVP, MCC, ICI, VT and BC was noted in the cyclophosphamide group and lipopolysaccharide group. Increased PVR, MVP, MCC, VT and BC were presented in the bladder outlet obstruction group. Therefore, we suggested that the urodynamic parameters could reflect the pathophysiological characteristics of DI induced by different causes, which could systematically benefit the diagnosis and treatment of overactive bladder.

Long-term versus short-term introvesical chemotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis of the published results of randomized clinical trials

In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several databases with words as mesh terms and free text words to find all eligible randomized clinical trials (RCTs) for the comparison of the two strategies of instillation durations. “Observed-Expected events research (O-E)” and “Variance (V)” for calculating hazard ratio (HR) were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were selected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were included in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI (0.89, 1.11), P=0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI (0.69, 1.00), P=0.05]. But patients were not suitable to receive long-term instillations with epirubicin (EPI) [HR=1.01, 95% CI (0.91, 1.13), P=0.78]. The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI (0.66, 1.39), P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.SummaryIn order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several databases with words as mesh terms and free text words to find all eligible randomized clinical trials (RCTs) for the comparison of the two strategies of instillation durations. “Observed-Expected events research (O-E)” and “Variance (V)” for calculating hazard ratio (HR) were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were selected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were included in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI (0.89, 1.11), P=0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI (0.69, 1.00), P=0.05]. But patients were not suitable to receive long-term instillations with epirubicin (EPI) [HR=1.01, 95% CI (0.91, 1.13), P=0.78]. The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI (0.66, 1.39), P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.