Therapeutic effects of sacral neuromodulation on detrusor underactivity / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effects of sacral neuromodulation (SNM) on detrusor underactivity (DUA).@*METHODS@#From December 2019 to April 2020, 6 patients with DUA who had been treated with SNM were assessed retrospectively. The average age was 58 years (46-65 years), with 3 males and 3 females. All the patients were diagnosed with DUA by urodynamics examination. Obstruction of bladder outlet was excluded through the cystoscopy. No patient had the history of neurological disease. All the patients were placed with the bladder colostomy tube before SNM. One female patient accepted the trans-urethral resection of bladder neck. Two male patients accepted the trans-urethral resection of prostate. All the 3 patients had no improvement of void symptom after the urethral operation. Before SNM, the average 24 h times of voiding was 23.8 (18-33), average volume of every voiding was 34.2 mL (10-50 mL), average residual volume was 421.7 mL (350-520 mL). The preoperative and postoperative 24 h urine frequency, average voided volume, and average residual urine volume were compared respectively.@*RESULTS@#Totally 6 patients underwent SNM with stage Ⅰ procedure. The operation time for stage Ⅰ procedure was 62-135 min (average 90 min). After an average follow-up of two weeks, stage Ⅱ procedure was performed on responders. Four patients accepted stage Ⅱ procedure (conversion rate 66.7%), the other two patients refused the stage Ⅱ procedure because the urine frequency did not reach the satisfied level. But all the patients had the improvement of residual urine volume. For the 4 patients at the follow-up of 10-15 months, the improvement of void was still obvious. For the all patients after stage Ⅰ procedure, the average 24 h urine frequency reduced to 13.5 times (9-18 times, P < 0.001), the average voided volume increased to 192.5 mL (150-255 mL, P < 0.001), and the average residual urine volume reduced to 97.5 mL (60-145 mL, P < 0.001). No adverse events, such as wound infection or electrode translocation were detected during an average follow-up of 11.3 months. Only one of the 4 patients who received the stage Ⅱ procedure did the intermittent catheterization for one time each day.@*CONCLUSION@#SNM provides a minimal invasive approach for the management of DUA.

Research Progress of the Roles of Ubiquitination/Deubiquitination in Androgen Receptor Abnormalities and Prostate Cancer / 中国医学科学院学报

Ubiquitin is a small molecule protein consisting of 76 amino acids,widely found in eukaryotic cells. The process by which ubiquitin binding to a specific protein is called ubiquitination. Deubiquitination is the reversed process of ubiquitination. Ubiquitination stimulates downstream signal,including complex assembly,protein conformation and activity changes,proteolysis,autophagy,guilt,chromatin remodeling,and DNA repair. More than 80% of eukaryotic protein degradation is mediated by the ubiquitination system,and ubiquitin-dependent proteolysis is an extremely complex process involving many biomolecular processes. By regulating protein homeostasis,ubiquitination can also regulate a variety of biological processes including cell cycle,cell proliferation,and apoptosis,which are closely related to tumorigenesis and progression. Many abnormalities of androgen receptor (AR) including AR gene amplification,mutation,shear mutation,and AR activity enhancement are closely related to prostate cancer progression. In particular,prostate cancer progression is regulated by the ubiquitination/deubiquitination processes. This article summarizes the recent research advances in the roles of ubiquitination/deubiquitination in AR abnormalities and prostate cancer.

Primary development of visual uroflow scale / 北京大学学报(医学版)

OBJECTIVE@#To develop the visual uroflow scale (VUS), analyze the relationship of VUS score and index of free uroflowmetry, assess urination function preliminarily and improve the work efficiency in the clinic.@*METHODS@#Male lower urinary tract symptoms (LUTS) patients, who attended the Department of Urology in Peking University People's Hospital from March 2016 to March 2017, were assessed for their urination function according to the Visual Uroflow Scale without help from clinicians before undertaking a free uroflowmetry test. And afterwards, a free uroflowmetry was undertaken, and variables including maximal flow rate (Qmax), the average flow rate (Qave) and voiding volume (VV) was obtained. During the study, 124 cases were collected and 53 cases met the inclusion and exclusion criteria and were included in the study cohort. The Spearman correlation analysis was used for analyzing the correlation of VUS scores with free uroflowmetry variables and age. The validity of VUS was evaluated.@*RESULTS@#Most of the patients could choose the very figure matched with self-condition by first instinct without any help from the clinician. The data were analyzed by Spearman correlation analysis. In the present study, voiding time was positively correlated with the VUS score (correlation coefficient, 0.62, P < 0.05). In the present cohort, the patients chose the third and fourth figures to take longer time to urinate, implying worse LUTS situation. Flow time and VUS scores were positively correlated (correlation coefficient, 0.61, P < 0.05). The patients with higher VUS scores would spend more time on urinate, no matter how long urinary hesitation was. Both Qmax and Qave were negatively correlated with the VUS score (correlation coefficient －0.54, －0.62, P < 0.05). The study illustrated that the VUS score suggested that the Qmax basically and further reflected the urination function. And its relationship to age revealed the decreased urination function of aging male, which had reached a consensus.@*CONCLUSION@#Development of VUS has helped the clinician assess the urination function preliminarily at the first time. Patients are assessed for a VUS score before getting surgery or receiving the drug for treatment, and can be re-assessed after. The VUS score can provide an objective quantitative basis to evaluate the treatment efficacy. In addition, considering that it is convenient, timesaving and easy to understand, the VUS is available for follow-up.

Outcome of surgical management and pathogenesis of female primary bladder neck obstruction / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effect of transurethral resection of bladder neck on primary female bladder neck obstruction and to analyze the expression of three kinds of sex hormone receptor (SR) in female bladder neck tissues diagnosed as primary bladder neck obstruction by the immunochemistry and statistics.@*METHODS@#The clinical data of 40 female patients, admitted into Peking University People's Hospital for difficulty of voiding during Oct.2008 and Dec.2013 and eventually diagnosed as bladder outlet obstruction (BOO) by urodynamics, were retrospectively reviewed. BOO was defined as a maximum flow rate (Qmax) less than 12 mL/s together with a detrusor pressure at maximum flow rate (Pdet Qmax) more than 25 cmH2O in urodynamic study in the absence of neurological disorders. Diagnosis was confirmed by the cystoscopy. Preoperative and postoperative AUASS scores were recorded and analyzed for observation of curative effects and complications. The immunochemical expression of SR of primary female bladder neck obstruction (PBNO) tissues and normal control was examined and applied to statistical analysis.@*RESULTS@#There were significant changes postoperatively in voiding scores, storage scores and total scores (P<0.001). Postoperatively, 1 patient newly presented with overactive bladder (OAB), 4 patients newly presented with hematuria, and 1 patient underwent cystostomy. The symptoms of urinary retention with overflow incontinence in 2 patients disappeared after the surgery, and 3 patients complicated with OAB complained without urgency. In addition, pre-hydronephrosis improved postoperatively in six patients. The subjective satisfactory rate to the surgery of TURBN was 77.5% (31/40). Sex hormone receptor, including androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR), expressed in both bladder neck tissues of normal control and PBNO patients. In PBNO group, the expression of PR was significantly lower than that of control group (P<0.05), while the other 2 SRs expressed with no significantly statistical difference. PBNO patients were divided into 2 groups, according to their symptoms scores, and the expression of SRs showed no significant differences among the mild, moderate and severe groups (P>0.05).@*CONCLUSION@#The transurethral bladder neck resection is valid in treating with female PBNO patients, with rarely occurrence of complications. PR expressed less in the female bladder neck tissues, and is possibly correlated with the occurrence of female PBNO.

Urodynamic classification of male patients with symptoms of overactive bladder and the outcome classification / 北京大学学报(医学版)

OBJECTIVE@#To introduce a urodynamic classification of male patients with symptoms of overactive bladder (OAB) and discuss its clinical significance in practice.@*METHODS@#From January 2015 to January 2017, there were 181 male patients from Peking University People's Hospital who were diagnosed clinically with OAB and underwent preoperative urodynamic test. Finally 126 male patients were enrolled in the research. Male OAB patients could be stratified into four groups based on the chief complaints (whether or not presenting urgency) and the results of urodynamic test (whether or not presenting detrusor overactivity and the ability to stop the involuntary contraction). The contents of this follow-up study included the basic information, the preoperative and postoperative scores of the OAB symptom score (OABSS), the preoperative and postoperative scores of the international prostate symptom score (IPSS), and the amount of the concomitant diseases.@*RESULTS@#According to the classification, the amounts of the four types of OAB patients were 32 (25.40%) for type I, 27 (21.43%) for type II, 59 (46.83%) for type III, and 8 (6.35%) for type IV, respectively. The data of their heights showed no statistical significance (P>0.05). The ages, weights and the amount of the concomitant diseases of type IV were obviously higher than those of the other three types (P<0.05). And the ages, weights and the amount of the concomitant diseases of the other three types had shown no statistical significance (P>0.05). The improvement of the OABSS and IPSS scores of the type IV were obviously inferior to the other three types (P<0.05). The improvements of the OABSS and IPSS scores of type III were obviously higher than those of the other three (P<0.05). The discrepancy of the OABSS and IPSS scores of type I and type II had shown no statistical significance (P>0.05).@*CONCLUSION@#Type IV has the worst outcome and type III has the best among the four types of OAB. And this classification system will certainly have a profound significance in guiding and directing our clinical diagnosis and treatments, and evaluating the prognosis of the patients with OAB.

Analysis of urodynamic study of female outpatients with lower urinary tract symptoms and follow-up of the patients with detrusor underactive / 北京大学学报(医学版)

OBJECTIVE@#To find out the prevalence of lower urinary tract symptoms (LUTS) and analyze the characteristics of the urodynamics diagnosis in female outpatients. To study the natural history of detrusor underactive (DU) by the followed up.@*METHODS@#A retrospective study of the female LUTS outpatients in Peking University People's Hospital from Jan. 2005 to Dec. 2015 was performed. The basic information and the urodynamic results of a total of 656 female outpatients were collected. The distribution of storage symptoms, voiding symptoms, complications and urodynamic diagnosis were analyzed. The symptoms and urodynamic results were compared among the groups, which were divided according to age, urodynamic diagnosis and diabetes mellitus. A follow-up of 163 female DU outpatients was performed, including the treatments and the American Urological Association symptoms scores (AUAss).@*RESULTS@#Frequency (25.03%) is the most common symptom in female outpatients, followed by stress urinary incontinence (20.04%), urgency (19.97%), and difficulty of voiding (17.32%). Stress urinary incontinence (SUI) accounted for the first (36.04%) of the whole outpatients, followed by the DU (24.08%), and bladder outlet obstruction (17.58%). The patients aged 51-60 years occupied the peak of almost all the diagnosis. There was a higher proportion of the young female patients than that of the middle and old patients diagnosed with no abnormal after the urodynamic study. The first, strong, urge and maximum bladder capacity were significantly larger in DU patients with diabetes than without diabetes. Follow-up results of the DU patients showed there was no significantly difference of the AUAss scores in both the two groups before and after the follow-up, but the quality of life decreased significantly.@*CONCLUSION@#Female LUTS outpatients showed a main complaint of storage symptoms. SUI ranked the first in female patients with LUTS. With the increase of age, bladder sensation and detrusor function decrease. In elderly patients, DU became the first ranked disease instead of SUI. Diabetes can affect the sensory function of bladder in patients with DU, and then increase the difficulty of voiding. The patients with DU, absent from treatment, experienced a lower quality of life.

Long-term follow-up of the efficacy of tension-free vaginal tape and trans-obturator tape for different types of stress urinary incontinence / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the long-term efficacy of tension-free vaginal tape (TVT)and trans-obturator tape (TOT)for different types of female stress urinary incontinence (FSUI).@*METHODS@#The clinical data of all female patients with stress urinary incontinence (SUI) who underwent mid-urethral slings (MUS) in Peking University People's Hospital from January 2008 to June 2016 were retrospectively analyzed, and all the patients were followed up. Based on the level of abdominal leak point pressure (ALPP), the patients with ALPP lower than or equal to 60 cmH2O (1 cmH2O=0.74 mmHg) were regarded as intrinsic sphincter deficiency (ISD) type, and the patients with ALPP higher than 60 cmH2O were regarded as non-ISD type. According to the degree of remission of leakage of urine by using the International Consultation on Incontinence Questionnaire Short Form (ICI-Q-SF), the surgical outcomes were divided into three categories: cured, improved or failed. The efficacy of TVT and TOT for different types of FSUI was evaluated by comparing the cure rate of TVT with the cure rate of TOT in ISD type and non-ISD type separately.@*RESULTS@#A total of 170 patients were included in this study. The patients were among 30-78 years, and the follow-up period were among 12-110 months. In the study, 117 patients belonged to non-ISD type. Of whom 30 underwent TVT with a cure rate of 86.7% (26/30), and the other 87 underwent TOT with a cure rate of 69.0% (60/87). The cure rate of TVT was higher than that of TOT in non-ISD type, however, Chi-square test showed that there was no significant difference (χ2=3.589, P>0.05). In addition, 53 patients belonged to ISD type, of whom 16 underwent TVT with a cure rate of 87.5% (14/16), and the other 37 underwent TOT with a cure rate of 51.4% (19/37). The cure rate of TVT was higher than that of TOT in ISD type, and Chi-square test showed that the difference was statistically significant (χ2=6.212, P<0.05).@*CONCLUSION@#For the treatment of FSUI, MUS can achieve satisfactory long-term efficacy. For non-ISD type, the cure rates of TVT and TOT are similar, while for ISD type, the cure rate of TVT is higher than that of TOT.

Comparison of effectiveness and complications between two different methods of augmentation cystoplasty / 北京大学学报(医学版)

OBJECTIVE@#To compare the effectiveness and complications between enterocystoplasty and small intestinal submucosa (SIS) cystoplasty through follow-ups of patients with augmentation cystoplasty in Peking University People's Hospital, offering alternative approach for future treatment.@*METHODS@#In this study, retrospective analyses were carried out in 10 patients who underwent enterocystoplasty or SIS cystoplasty in Peking University People's Hospital from November 2011 to December 2016. Clinical data were collected including medical history, surgical procedures, laboratory examinations and complications. And then regular follow-ups were developed. Ten patients were separated into groups of enterocystoplasty (n=6) and SIS cystoplasty (n=4), to compare their outcomes.@*RESULTS@#Ten patients all completed the follow-up interview. Five cases underwent augmentation cystoplasty with sigmoid colon, one with ileum and four with SIS cystoplasty successfully. The mean operative time was (302.0±66.6) min, and blood loss was (167.0±135.0) mL. The outcomes of the group of SIS cystoplasty were better in respects of the time of operation, intestinal function recovery, postoperative hospitalization duration and drainage removal. The average scores of American Urological Association symptom score (AUASS), overactive bladder syndrome score (OABSS), International Consultation on Incontinence questionnaire short form (ICI-Q-SF), and O'Leary-Sant Questionnaire were all improved in two groups. Two cases carried clean intermittent self catheterazion and two used long-term indwelling catheter. There were three patients with dilations of renal pelvises and ureters consistently or during bladder was filling preoperatively, and the situations were not going bad after the operations. The short-term complications included two cases of postoperative infection, one case of mild intestinal obstruction and one case of metabolic acidosis. The long-term complications included one case of ureteroinstestinal anastomosis strictures, three of urinary tract infection and one of long-term metabolic acidosis.@*CONCLUSION@#Enterocystoplasty and SIS cystoplasty are both effective operations to improve symptoms and protect upper urinary function, with no severe complications. Cystoscopic results showed satisfactory mucosa regeneration after SIS cystoplaty in refractory interstitial cystitis/painful bladder syndrome. But the number of patients included were quite small and the follow-up period was not long enough. Prospective control study of larger number of patients with longer follow-ups are expected to find out the effectiveness and safety of SIS cystoplasty.

Clinical Features and Diagnosis of Encrusted Bladder Cancer / 中国医学科学院学报

Bladder cancer is a urological malignant tumor with high morbidity and mortality. Masses protruding into the bladder cavity is an important feature for clinical diagnosis of bladder cancer. However,patients with encrusted bladder cancer(EBC)do not present with masses protruding into the bladder cavity and thus this malignancy is often misdiagnosed. Four patients were admitted in Peking University People's Hospital from July 2015 to February 2017. All of them were males aged 40 to 77 years(mean:58 years). Patients were mainly manifested as frequent urination,urgency,nocturia,and decreased bladder capacity,with or without difficulty of voiding.Although the bladder walls were markedly thickened,there was no obvious mass on imaging scans. Three patients received urodynamic test,which showed the maximum capacity of the bladder was 41 to 128 ml(mean:91 ml). One patient presented with gross hematuria,two patients presented with microscopic hematuria,and the remaining one patient had no hematuria. No mass was observed by cystoscopy. All of the patients were diagnosed with bladder cancer by repeated biopsy or intraoperative frozen section analysis.

Relationship of EpCAM expression and DNA copy number alteration in colorectal carcinoma cells / 临床与实验病理学杂志

Purpose To investigate the clinical pathology significance of epithelial cellular adhesion molecule (EpCAM, CD326) expression in colorectal carcinoma cells. Methods Flow cytometry and immunofluorescence assay were used to detect EpCAM expression in 55 cases of fresh colorectal cancer tissues and adjacent normal mucosa. The percentage of positive cells (PPC) and mean fluorescence index (MFI) were calculated. Correlation of EpCAM expression with DNA ploidy change and its value were investigated in the early diagnosis of colorectal cancer. Results The values of PPC and MFI were significantly higher in colorectal carcinoma tissue than that in the normal colorectal tissue [(PPC: (83.48 ± 7.07)％ vs (43.56±5.29)％, t =39.22, P＜0.001. MFI: 28.90(19.60-45.89) vs4.89(3.79-6.28), Z=-6.45, P＜0.001) ]. There were also significant differences (P＜0.01) in the values of PPC and MFI between invasive type and ulcer types, between well-and moderately-differentiated and poorly-differentiated cancers, between Dukes stages A + B and C + D, (between pTNM stages I+ II and III + IV, between pTl + T2 and pT3 + T4, and between pNO and pNl. DNA content analysis showed that DNA polyploid was detected in 39 of 55 colorectal carcinoma (70.90％ ). The DNA index (DI) and ploid were correlated with differentiation degree and Dukes stages, but uncorrelated with lymph node metastasis. At the same time, in the EpCAM positive cases, DI was increased with increased expression of EpCAM (r = 0.668, P =0.000) and the proliferation index of cells in S phase ratio(Sphase fraction, SPF) (r1 =0.664, P1 =0.000, r2 =0.651, P2 = 0.000 ). Conclusion EpCAM expression is obviously upregulated in colorectal carcinoma, and it is closely correlated with the invasion, metastasis and proliferation of tumor cells. The combination of EpCAM expression and DNA content analysis provides references to the early diagnosis and prognosis evaluation in colorectal carcinoma.

Clinical application of partial cystectomy with augmentation cystoplasty for invasive bladder cancer in elderly patients / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical effect and safety of biological patch applied in elderly patients with invasive bladder cancer who underwent massive partial cystectomy with augmentation cystoplasty.@*METHODS@#The clinical data of 2 patients with invasive bladder cancer from October 2016 to March 2017, who underwent the massive partial cystectomy with augmentation cystoplasty were retrospectively reviewed. Case one was an 87-year-old man, with tumor located on the bladder anterior wall, ranging from 5.5 cm×2.5 cm, and the grade of American Society of Anesthesiologists (ASA) being III. Case two was a 77-year-old female, whose lesion was located on the right anterior wall, ranging from 5.2 cm×4.0 cm, and the grade of ASA being II. Both of the patients received a massive partial cystectomy with augmentation cystoplasty. The operative time, estimated blood loss, perioperative and postoperative data and follow-up data, including cystoscopy and urodynamics were recorded and compared. When the P value was less than 0.05, it was statistically significant.@*RESULTS@#All the operations were successfully performed. The average operative time was (155.0+35.4) min, mean estimated intraoperative blood loss was 20 to 100 mL, and the mean postoperatively hospital stay was eight days. During the 10 to 14 months' follow-up periods, no local recurrence or distant metastasis occurred. Urodynamic data: the maximum urinary flow rate was 16.5 mL/s, and the maximum bladder capacity was 303 mL. The two patients urinated 3-4 times in the day time, 0 to 3 times in the night, 200-300 mL each time, on average. The American Urological Association symptom score was 3 to 5. Partial cystectomy, applied to aged patients with multiple complications and high risk of surgical anesthesia, was able to reduce surgery related complications. For patients with tumor of small size, the normal bladder wall would be enough to recover functional capacity for urine storing after partial cystectomy. For patients with large lesions range and small normal bladder tissues, augmentation cystoplasty would help recover bladder capacity on the condition of negative margin.@*CONCLUSION@#Massive partial cystectomy with augmentation cystoplasty is safe and effective. It could decrease perioperative morbidity and keep the quality-of-life benefits of bladder preservation, which is worthy of further application for some selected invasive bladder cancer in elderly patients.

Synthesis and investigation on antidiabetic activity of 4-(1-aryl-3-oxo-5-phenylpentylamino) benzenesulfonamide / 药学学报

Searching for new antidiabetic lead compound, 4-(1-aryl-3-oxo-5-phenylpentylamino) benzenesulfonamides were designed and synthesized directly by three component one-pot condensation of 4-phenyl-2-butanone and sulfanilamide with some aromatic aldehydes at an yield of 23%-97%. The chemical structures of the twelve new Mannich bases were confirmed by 1H NMR, 13C NMR, FTIR, ESI-MS and HR-MS. The screening results of antidiabetic activity indicated that most of these title compounds possess alpha-glucosidase inhibitory activity, among which compound le is the strongest one. And compound 11 possesses good peroxisome proliferator-activated receptor response element (PPRE) agonist activity. The structure-activity relationship of these new beta-amino ketones containing benzenesulfonamide unit was also discussed preliminarily.

Synthesis and preliminary evaluation of antidiabetic activity of 4-(3-(4-bromophenyl)-3-oxo-1-arylpropylamino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide / 药学学报

Diabetes mellitus is a common metabolic disease with a high and growing prevalence affecting 4% of the population worldwide, the development of safe and effective therapeutic drug is the major thrust for chemists and pharmacists. To search for active antidiabetic lead compound, we designed and synthesized some novel beta-amino ketone derivatives containing sulfamethoxazole moiety directly through Mannich reaction of sulfamethoxazole, 4-bromoacetophenone and some aromatic aldehydes catalyzed by concentrated hydogen chloride or iodine in the solution of ethanol at 24-40 degrees C with convenient operation, mild reaction condition and satisfactory yield (32%-90%). Their chemical structures were characterized by 1H NMR, 13C NMR, MS and HR-MS. Biological activity tests showed that, in the range of low concentration (5-10 microg x mL(-1)), these title compounds to a certain degree possess protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and a-glucosidase inhibitory activity, moreover, some could activate peroxisome proliferator-activated receptor response element (PPRE) moderately. The PPRE agonist activities of seven compounds are almost 40% of that of Pioglitazone (the positive control), compound 12 shows the strongest activity (66.35%) among them. Thus, it was found that some of 4-(3-(4-bromophenyl)-3-oxo-1-arylpropylamino)-N-(5-methyl-isoxazol-3-yl) benzenesulfonamide containing sulfamethoxazole moiety exhibited antidiabetic activity for the first time.

Preventive effects of emodin on cerebral ischemia injury and expression of the inflammatory factors in rats with cerebral ischemia / 中国中药杂志

<p><b>OBJECTIVE</b>To assess emodin antagonism to cerebral ischemia injury, and to discuss the mechanism of emodin inhibiting the inflammatory cascade reaction from the levels and expressions of cytokines.</p><p><b>METHOD</b>Rats were divided into sham-operated group, model group, Ligustrazine group and emodin groups (low, middle, high dosage). After focal cerebral ischemic model of cerebral middle artery occlusion was duplicated with nylon thread, we took the speciments after ischemia 6 hours, observed the changes of the evaluating score of neural symptoms, brain water ratio and cerebral infarction area, determined the levels of TNF-alpha, IL-beta and TGF-beta in rats brain tissue by radioimmunoassay, detected the expressions of TNF-alpha and VCAM-1 by immunohistochemistry, and measured VCAM-1-mRNA expression by in-situ hybridization.</p><p><b>RESULT</b>Compared with sham-operated group, the evaluating score of neural symptoms, brain water ratio and cerebral infarction area of rats in model group were higher (P < 0.01) , the levels of TNF-alpha and IL-1beta of rats brain tissue in model group increased, while the level of TGF-beta was lower, and the expressions of TNF-alpha and VCAM-1 increased (P < 0.01). The evaluating score of neural symptoms, brain water ratio and cerebral infarction area improved obviously in every emodin group, especially in emodin low dosage group. Levels of TNF-alpha, IL-1beta and the expressions of TNF-alpha and ICAM-1 in emodin low dosage group and Ligustrazine group were lower, while the level of TGF-beta was higher. Compared with Ligustrazine group, the changes aboved are more significant in emodin low dosage group (P < 0.01).</p><p><b>CONCLUSION</b>The increase of inflammatory cascade reaction mediated by various cytokines such as TNF, IL-1beta, ICAM-1 and the decrease of TGF protection are the important mechanism of cerebral ischemia injury. The mechanism of emodin antagonism to cerebral ischemia injury may be implemented by inhibiting inflammatory cascade reaction and increasing the brain protective factors, such as TGF.</p>

Reproductive toxicity of metadoxine in rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the reproductive toxicity of metadoxine.</p><p><b>METHODS</b>Male and female rats were given metadoxine before pregnancy and early gestation, i.e. to feed metadoxine to male rats for 60 days before copulation and continue feeding during copulation, and feed metadoxine to female rats for 14 days before copulation.</p><p><b>RESULTS</b>No significant toxic effect was observed in the 400 mg/kg group. A few rats showed paralysis of hind leg in the 800 mg/kg group. The dosage of 1 600 mg/kg caused significant paralysis of hind legs, emaciation, and reduced weight gain. In the 1600 mg/kg group, the mating rate of male rats was significantly affected (P < 0.01). In the 800 and 1 600 mg/kg group, fertility of male rats was markedly reduced (P < 0.01). In the 800 mg/kg group, the effect on sperm counts of epididymis of male rats was markedly reduced (P < 0.05). In the 1 600 mg/kg group, testicle weight and body weight ratio and sperm counts of epididymis rate were significantly (P < 0.001) reduced. In the 1 600 mg/kg group, the fertility rate of female rats was remarkably (P < 0.001) reduced. In the 800 mg/kg group, the weight gain of pregnant rats was significantly reduced (P < 0.001). In both the 800 and 1 600 mg/kg groups, the gestation rate was greatly reduced (P < 0.001). In the 800 mg/kg group, mortality rate before nidation (P < 0.001) and average live fetus number were significantly reduced (P < 0.05). In the 400 mg/kg group, the fetal weight was significantly reduced (P < 0.001). In the 800 mg/kg group, body length, tail length, body weight and sternum development of fetal rats were significantly affected (P < 0.001).</p><p><b>CONCLUSION</b>Under the presented experimental conditions, metadoxine has no teratogenic effects on SD rats and the no effect dose is 400 mg/kg. And the no effect dose for the developmental toxicity is less than 400 mg/kg.</p>