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ObjectiveTo investigate the mechanism of Yiqi Huoxue Tongluo prescription （YHTP） in the treatment of diabetic neuropathic pain （DNP）. MethodNinety SPF-grade SD male rats were randomized into blank， model， low- （2.25 g·kg-1）， medium- （4.5 g·kg-1）， and high-dose （9 g·kg-1） YHTP， and mecobalamin （0.175 mg·kg-1） groups. Except those in the blank group， the rats in the remaining 5 groups were fed with a high-fat and high-glucose diet and subjected to intraperitoneal injection of low-dose （35 mg·kg-1） streptozotocin （STZ） to establish the model of DNP. The sciatic nerve conduction velocity in DNP rats was measured by the neurophysiological method， and the levels of interleukin-6 （IL-6）， IL-1β， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of glial fibrillary acidic protein （GFAP） and extracellular signal-regulated kinase （ERK） in the spinal cord. Western blot was employed to measure the protein levels of GFAP and phosphorylated ERK （p-ERK）， and immunofluorescence staining to measure the fluorescence intensity of GFAP and p-ERK in the spinal cord. In the cell experiments， 100 mmol·L-1 high glucose was used to induce the activation of astrocytes （CTX-TNA2） for the modeling of nerve cell injury. The cells were randomized into the normal， model， drug-containing serum （10% YQHT）， inhibitor ［10 mol·L-1 corynoxeine （COR）］， drug-containing serum + inhibitor （10% YHTP + 10 mol·L-1 COR） groups. The levels of pro-inflammatory factors （TNF-α and IL-1β） and the anti-inflammatory factor IL-10 in CTX-TNA2 cells were determined by ELISA， and the protein levels of GFAP and p-ERK in CTX-TNA2 cells by Western blot. ResultThe animal experiments showed that compared with the blank group， the model group presented reduced mechanical withdrawal threshold （MWT）， thermal work limit （TWL）， and nerve conduction velocity， elevated levels of fasting blood glucose， IL-1β， TNF-α， and IL-6， and up-regulated protein levels of GFAP and p-ERK， and mRNA levels of ERK1， ERK2， GFAP （P<0.01）. Compared with model group， YHTP increased the MWT， TWL， and sciatic nerve conduction velocity （P<0.01）， lowered the levels of IL-1β， TNF-α， and IL-6 （P<0.01）， and down-regulated the protein levels of GFAP and p-ERK， and mRNA levels of ERK1， ERK2， GFAP in the spinal cord （P<0.05， P<0.01）. The cell experiments showed that compared with the blank group， the model group had decreased survival rate， elevated levels of pro-inflammatory factors， and up-regulated protein levels of ERK and GFAP （P<0.01）. Compared with the model group， the YHTP-containing serum lowered the levels of IL-1β and TNF-α （P<0.05， P<0.01）， elevated the level of IL-10 （P<0.01）， and down-regulated the protein levels of ERK and GFAP （P<0.01）. ConclusionYHTP may inhibit the activation of astrocytes by inhibiting the ERK signaling pathway to reduce inflammation and thus relieve DNP.
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Objective:To summarize the ideal strategy for the treatment of female hypospadias.Methods:The data of 12 female patients with hypospadias admitted to the Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2011 to December 2019 were retrospectively analyzed. The patients was (31.0±16.6) years old (7-67 years old). Among them, 3 cases had a history of pelvic fracture trauma, 3 cases had a history of birth trauma, and the remaining 6 cases had no history of trauma and surgery. Among them, there were 6 cases of congenital hypospadias and 6 cases of acquired hypospadias. The clinical manifestations were urinary incontinence in 6 cases and dysuria in 6 cases. Examination of the normal position of the external opening of the genital urethra did not show the opening of the urethra, but moved down to different parts of the anterior wall of the vagina. All patients underwent urethral lengthening. For congenital hypospadias, the urethral plate is used to cut the coiled tube during the operation to prolong the urethra. For acquired hypospadias, the stenotic urethra was enlarged and lengthened with a labial pedicled flap coil. The subcutaneous fat pad of the labia majora was mobilized and transferred to the outside of the newly constructed urethra to prevent the occurrence of urethro-vaginal fistula and increase the pressure of the urethra. Five patients with significant urinary incontinence underwent bladder neck reconstruction at the same time. Anatomical success of the procedure was defined as the appearance of a normal-shaped external urethral opening beneath the clitoris. Functional success was defined as the absence of moderate to severe urinary incontinence after surgery, and the maximum urinary flow rate was >15ml/s during the 12-month follow-up period.Results:All operations were successfully completed. All patients had no perioperative complications, and were followed up for 18-96 months, with an average of 57.3±32.5 months. All patients were able to urinate spontaneously after operation, 4 cases of urinary incontinence disappeared, and 2 cases improved significantly; 4 cases of patients with strenuous urination urinated smoothly. The remaining 2 cases still complained of dysuria after operation, which was solved by subsequent urethral dilatation. The anatomical repair success rate was 100.0%(12/12) and the functional success rate was 83.3% (10/12).Conclusions:Urethral lengthening is an effective method for female hypospadias. The pedicled fat pad helps to increase urethral pressure and prevent fistulas. For female patients with hypospadias and severe urinary incontinence, bladder neck reconstruction is an ideal method. of the technique.
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This study retrospectively analyzed the clinical data of 28 male patients with urethral stricture who had complications during urethrography, including 14 cases of infection, 8 cases of urethral bleeding, 5 cases of contrast agent hypersensitivity, and 1 case of bladder rupture. The infection manifested as acute cystitis in 11 cases, acute pyelonephritis in 1 case, acute epididymitis in 1 case, and sepsis in 1 case. Hypersensitivity reaction was mild in 3 cases, moderate and severe in 2 cases. A child with bladder rupture was immediately transferred to open surgery for bladder repair. All patients were cured by corresponding treatment. The complications of urethrography have various manifestations and different degrees of severity, so we should pay attention to prevention and proper treatment.
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Objective:To investigate the influencing factors of blood glucose fluctuation after surgery for type A aortic dissection in non-diabetic patients.Methods:A total of 109 patients with non-diabetic type A aortic dissection who underwent surgical treatment in Ningbo Medical Center Li Huili Hospital from Dec. 2016 to Mar. 2022 were selected as the research subjects. Logistic regression analysis was used to explore the influencing factors of blood glucose fluctuation in non-diabetic patients with type A aortic dissection surgery, and a nomogram model of blood glucose fluctuation in non-diabetic patients with type A aortic dissection surgery was constructed.Results:Logistic regression analysis showed that BMI≥24 kg/m 2, poor sleep quality, depression, cardiopulmonary bypass time>5 h and intraoperative bleeding were the risk factors for postoperative blood glucose fluctuation in non-diabetic type A aortic dissection patients ( P<0.05). The C-index of the nomogram model was 0.746 (95% CI: 0.711-0.781) ; the calibration curve was in good agreement with the ideal curve; the AUC of the nomogram model was 0.804. Conclusion:BMI≥24 kg/m 2, poor sleep quality, depression, cardiopulmonary bypass time>5 h and intraoperative bleeding are risk factors for postoperative blood glucose fluctuation in non-diabetic type A aortic dissection patients.
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OBJECTIVE To compare the efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy， and to provide evidence-based reference. METHODS The databases including CNKI， VIP， China Biomedical Literature Database， Wanfang data， PubMed， Embase and Cochrane Library were searched for the RCTs about levetiracetam （trial group） and valproic acid （control group） were collected from the inception to October 1st， 2021. After literature screening and data extraction， the quality of included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0 and RevMan 5.3 software were used for meta-analysis， sensitivity analysis and bias risk analysis. RESULTS A total of 33 RCTs were included， involving 3 116 patients in total. The results of the meta-analysis showed that the effective rate of trial group was significantly higher than control group [RR＝1.06， 95%CI （1.02， 1.11）， P＝0.003]. The subgroup analysis according to different courses of treatment showed that there was no statistical significance in the effective rate between 2 groups after 1 and 3 months of treatment （P＞0.05）； after 6 months of treatment， the effective rate of trial group was significantly higher than that of control group （P＜0.05）. The incidence of adverse drug reaction in trial group was significantly lower than control group [RR＝0.50， 95%CI （0.41， 0.61）， P＜0.000 01]； among specific adverse drug reactions， the incidence of nausea and vomiting in trial group was significantly lower than control group （P＜0.05）； but there was no statistical significance in the incidence of rash， drowsiness， abnormal mood， loss of appetite， dizziness or headache （P＞0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS The short-term efficacy （1， 3 months） of LEV is similar to that of VPA in the treatment of pediatric epilepsy， but long-term efficacy （6 months） of LEV is better than that of VPA； moreover， LEV shows better safety in digestive system.
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Visceral leishmaniasis is a parasitic disease transmitted by Phlebotomus chinensis that poses a great threat to human health. Historically, visceral leishmaniasis was predominantly prevalent in northwestern regions of Sichuan Province. Following the founding of the People’s Republic of China, large-scale integrated interventions had been implemented in visceral leishmaniasis-endemic areas of Sichuan Province, including identification and treatment of visceral leishmaniasis patients, elimination of infected dogs, Ph. chinensis control and health education. This review summarizes the prevalence of visceral leishmaniasis, discusses the control strategy of visceral leishmaniasis and analyzes the challenges of elimination of visceral leishmaniasis based on the One Health concept in Sichuan Province, so as to provide insights into elimination of visceral leishmaniasis in the province.
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This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.
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Schisandra/chemistry , Network Pharmacology , Drugs, Chinese Herbal/chemistry , Chemical and Drug Induced Liver Injury/drug therapyABSTRACT
We retrospectively analyzed the clinical data of 21 patients diagnosed with BPH combined with mild urethra stenosis from January 2018 to December 2020. 12 patients underwent holmium laser enucleation of prostate (HoLEP). There were 3 cases of serious urethra stenosis requiring repeat surgical treatment after surgery, 9 cases of unobstructed voiding, 4 cases of reverse ejaculation and 2 cases of temporary urinary incontinence. 9 patients underwent laparoscopic simple prostatectomy (LSP) and all patients had unobstructed voiding. There were no cases of severe urethral stricture, temporary urinary incontinence and retrograde ejaculation in LSP group. LSP has reduced the risk of a repeat urethral surgery because of transurethral operation increasing the degree of urethra stenosis.
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There are few reports on laparoscopic repair of traumatic atresia of bladder neck. In this study, three patients with traumatic atresia of bladder neck were repaired by laparoscopic surgery, and the surgery was successfully completed. During postoperative follow-up, the patients had smooth urination, no urinary incontinence and sexual function damage, and laparoscopic surgery was effective in repairing traumatic atresia of bladder neck.
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Objective:To identify the pathogens isolated in the subperiosteal abscesses from the pediatric patients with acute osteomyelitis and to investigate the characteristics of bacterial drug resistance.Methods:A retrospective study was conducted on children with acute septic osteomyelitis who were hospitalized in the Children's Hospital, Zhejiang University School of Medicine from January 1, 2011 to March 1, 2018. The results of bacterial cultures isolated from the subperiosteal abscesses or bone marrow fluid were collected. The Merier automatic bacterial identification system (i.e., Vitek) was used to identify the bacteria and to assess the drug sensitivity.Results:(1) A total of 104 pediatric patients were included and 60 (57.7%) were male. Sixty-six strains of pathogens were isolated from 65 patients (62.5%). Among them, 53 strains (51.0%) were Staphylococcus aureus; 3 strains were Escherichia coli; 2 strains (1.9%) were Pseudomonas aeruginosa; 2 strains (1.9%) were Streptococcus pneumoniae, 2 strains (1.9%) were Ochrobactrum anthropi, and 4 strains (3.8%) were other bacteria. Pathogens were not found in 39 patients (37.5%). (2) Staphylococcus aureus accounted for 81.5% (53/65) of the pathogen-positive cases. Among them, 23 strains (43.4%) were methicillin-resistant Staphylococcus aureus (MRSA). Aureus-positive children were statistically significantly older ( P=0.028), heavier ( P=0.040) and had higher C-reactive protein (CRP) level ( P=0.038) than the aureus-negative children. (3) All the 53 Staphylococcus aureus strains were resistant to penicillin and 56.6% of them were only sensitive to benzocillin. The resistance rates to compound sulfamethoxazole, tetracycline, clindamycin and erythromycin were 11.3%, 30.2%, 67.9% and 69.8%, respectively. The sensitivity rate of the strains to furantoin was 90.2%. All strains were sensitive to quinupristin/dalfopristin, linezolid, rifampicin, tigecycline, levofloxacin, moxifloxacin, ciprofloxacin and vancomycin. There was 69.8% of the strains resistant to three or more different types of antibiotics. Conclusions:Staphylococcus aureus is the most common pathogen that causes the acute septic osteomyelitis in children, and the resistance rate to Benzocillin is relatively high. Therefore, Benzocillin and Clindamycin, as the traditionally-used drugs, should not be considered as the first choice when empirically using intravenous antibiotics. In the present study, pathogens in 39 patients (37.5%) were not detected in their subperiosteal abscesses or bone marrow fluid, so further effort should be made to investigate the etiology of these patients.
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Objective:To explore the treatment experience of holmium laser enucleation of prostate (HoLEP) with preservation of longitudinal urethral mucosa at 12 o’clock for benign prostatic hyperplasia (BPH) with small-medium gland.Method:From October 2018 to April 2021, 256 patients diagnosed BPH with small-medium gland(prostate volume 30-60 ml)were retrospectively analyzed, including general information, way of operation, intraoperative parameters and follow-up data. From October 2018 to June 2020, 186 BPH patients underwent conventional HoLEP, which did not retain longitudinal urethral mucosa at 12 o’clock as a conventional operation group. From July 2020 to April 2021, 70 BPH patients underwent modified HoLEP, which retained longitudinal urethral mucosa at 12 o’clock as a modified operation group. There was no significant difference between the two groups( P>0.05) in term of the age[(70.5±4.4)years old vs.(68.5±3.2)years old], Q max[(7.5±2.8)ml/s vs.(7.5±2.1)ml/s], IPSS[(20.3±4.6)vs.(21.4±3.7)], QOL[(4.5±1.0)vs.(4.2±1.4)], postvoid residual volume[(126.9±29.36)ml vs.(132.2±32.3)ml], PSA[(1.5±1.3)ng/ml vs.(1.8±1.1)ng/ml] and prostate volume[(48.1±11.1)ml vs.(48.0±12.7)ml]. Both groups were treated with "trefoil" enucleation of prostate. The modified group was improved compared with the conventional group by retaining a 12 o’clock longitudinal urethra mucosa from the bladder neck to the apex of the prostate. The technical improvements were as follows: ①the left lobe of prostate was removed from at 5 o’clock at the verumontanum to 1 o’clock at the prostate apex along the gap between the hyperplasia gland and the surgical envelope; ②the right lobe was removed from 7 o’clock at the verumontanum to 11 o’clock at the apex; ③the urethra mucous membrane was cut vertically from 1 and 11 o’clock at the bladder neck to 1 and 11 o’clock at the apex respectively, and retaining the longitudinal mucous membrane between 11 and 1 o’clock (including 12 o’clock). Efficacy and postoperative complications of the two groups were compared. Results:The difference between the conventional group and the modified group in operation time[(36.5±10.4)min vs.(40.7±9.7)min], enucleated glandular weight[(35.5±12.2)g vs.(31.6±10.4)g], hemoglobin decline[(6.1±2.2)g/L vs.(5.6±2.5) g/L], postoperative hospitalization time [(1.2±0.2)d vs.(1.5±0.4)d]and catheter indwelling duration[(2.3±1.3)d vs.(2.0±1.0)d] were not statistically significant ( P>0.05). There were 252 patients for follow-up, including 183 cases in the conventional group and 69 cases in the modified group, and 4 cases were lost to follow-up. Mean time of follow-up was 8.4 months. In both groups, postoperative IPSS were 5.4±2.3 and 5.9±1.2 respectively, QOL1.5±0.3 and 2.0±1.0 respectively, Q max(24.3±9.2)ml/s and (22.5±11.3)ml/s respectively and postvoid residual volume (8.3±4.5)ml and (7.7±2.9)ml respectively, which were significantly different from that before the operation ( P<0.05). However, there was not significant difference between the two groups ( P>0.05). The postoperative immediate urinary continence rate of the conventional group and modified group were 85.2% (156/183), 98.6% (68/69), respectively, and two groups had statistical differences ( P<0.05). Incidence of postoperative bladder neck contraction were 4.4% (8/183) and 0 respectively in the conventional and modified group, whose difference was significant( P<0.05). Conclusions:HoLEP with preservation of longitudinal urethral mucosa at 12 o'clock is the same effective as conventional operation in the treatment of BPH with small-medium gland, likewise it could significantly improve immediate urinary continence rate and reduce the incidence of bladder neck contraction.
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Objective:To explore the feasibility of pretargeting technique for immunoPET with epidermal growth factor receptor (EGFR) monoclonal antibody in EGFR positive/negative tumor bearing mice.Methods:Cetuximab- Trans-cyclooctene (TCO)was obtained by modifying Cetuximab with TCO- N-hydroxysuccinimide (NHS). 2, 2′-((6-amino-1-(4, 7-bis-(carboxymethyl)-1, 4, 7-triazonan-1-yl)hexan-2-yl)azanediyl)-diacetic acid (L-NETA)was used as a chelating agent to prepare the radioligand 68Ga-L-NETA-tetrazine (Tz), then the labeling rate and in vitro stability of the product were determined. Human basal breast cancer cells MDA-MB-468 (EGFR+ ) and MDA-MB-231 (EGFR-) were cultured in vitro. In vitro experiments were performed to explore the specificity of the probe and the feasibility of pretargeting technique. Nude mice (Balb/c-nu) bearing xenografts of the above two cell lines were established. Cetuximab-TCO (50 μg) was injected into the tumor-bearing mice in advance, then 68Ga-L-NETA-Tz was injected at different time points (48, 36, 24 and 12 h), and pretargeting was realized through " click chemistry" . Small-animal PET imaging and biodistribution were performed to evaluate pharmacokinetic properties and specificity of the probe. The one-way analysis of variance was used to compare the data. Results:The 68Ga-L-NETA-Tz molecular probe was successfully prepared with the labeling yield >95%, and the radiochemical purity was >95% after 2 h. Cetuximab-TCO and 68Ga-L-NETA-Tz were added to MDA-MB-468 cells successively, and the cell uptake rate reached (0.69±0.04)% at 1 h, which demonstrated the feasibility of the pretargeting technique. PET imaging and biodistribution results showed that the best imaging results were obtained in 36 h pre-injection group, in which the tumor uptake was the highest ((0.77±0.05) percentage activity of injection dose per gram of tissue (%ID/g), 1 h) and the tumor/muscle ratio was optimal (4.67±0.46); the tumor uptake in the blocking group, the group without injecting Cetuximab-TCO, and the MDA-MB-231 group were significantly lower ((0.35±0.01), (0.39±0.05), (0.45±0.10) %ID/g; F=15.50, P=0.002). Conclusions:EGFR targeted immunoPET imaging is successfully performed in mouse models of breast cancer by injecting Cetuximab-TCO and 68Ga-L-NETA-Tz successively. It provides an effective method for immunoPET imaging of monoclonal antibodies.
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OBJECTIVES@#To reduce the dimension of characteristic information extracted from pelvic CT images by using principal component analysis (PCA) and partial least squares (PLS) methods. To establish a support vector machine (SVM) classification and identification model to identify if there is pelvic injury by the reduced dimension data and evaluate the feasibility of its application.@*METHODS@#Eighty percent of 146 normal and injured pelvic CT images were randomly selected as training set for model fitting, and the remaining 20% was used as testing set to verify the accuracy of the test, respectively. Through CT image input, preprocessing, feature extraction, feature information dimension reduction, feature selection, parameter selection, model establishment and model comparison, a discriminative model of pelvic injury was established.@*RESULTS@#The PLS dimension reduction method was better than the PCA method and the SVM model was better than the naive Bayesian classifier (NBC) model. The accuracy of the modeling set, leave-one-out cross validation and testing set of the SVM classification model based on 12 PLS factors was 100%, 100% and 93.33%, respectively.@*CONCLUSIONS@#In the evaluation of pelvic injury, the pelvic injury data mining model based on CT images reaches high accuracy, which lays a foundation for automatic and rapid identification of pelvic injuries.
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Algorithms , Bayes Theorem , Data Mining , Least-Squares Analysis , Support Vector MachineABSTRACT
Objective:To investigate the effects of desloratadine combined with Tongqiao Biyan capsule on allergic rhinitis. Methods:100 patients with allergic rhinitis who received treatment in The Affiliated Hospital of Medical College of Ningbo University from February 2018 to February 2020 were included in this study. They were randomly assigned to receive treatment with either desloratadine tablets (control group, n = 50) or desloratadine tablets combined with Tongqiao Biyan capsule (observation group, n = 50) for 21 days. Improvement in clinical symptoms and changes in inflammatory factors were observed in each group. Results:Scores of nasal itch, nasal obstruction, runny nose, and sneezing in the observation group were (1.42 ± 0.10) points, (1.20 ± 0.13) points, (1.25 ± 0.13) points, and (1.33 ± 0.14) points, respectively, which were significantly lower than those in the control group [(1.80 ± 0.12) points, (1.68 ± 0.15) points, (1.68 ± 0.11) points, (1.68 ± 0.13) points, t = 17.20, 17.10, 17.85, 12.95, all P < 0.001]. After treatment, interleukin -4, -6, -8 levels in the observation group were (16.12 ± 5.05) ng/L, (5.33 ± 2.10) ng/L, (37.16 ± 9.80) ng/L, respectively, which were significantly lower than those in the control group [(21.52 ± 5.58) ng/L, (8.12 ± 2.15) ng/L, (48.55 ± 9.65) ng/L, t = 5.07, 6.56, 5.86, all P < 0.05]. Interferon-γ level was significantly higher in the observation group than in the control group [(26.58 ± 2.58) ng/L vs. (23.68 ± 2.69) ng/L, t = 5.50, P < 0.001]. After treatment, the total score of the quality of life questionnaire was significantly higher in the observation group than in the control group [(61.58 ± 8.57) points vs. (40.98 ± 8.35) points, t = 12.17, P < 0.001]. There was no significant difference in total incidence of adverse reactions between observation and control groups [10.00% (5/50) vs. 14.00% (7/50), χ2 = 0.38, P > 0.05]. Conclusion:Desloratadine combined with Tongqiao Biyan capsule can better improve the symptoms of allergic rhinitis and better reduce inflammation without increasing adverse drug reactions compared with desloratadine alone.
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Magnoliae Officinalis Cortex(Houpo) can treat peptic ulcer disease(PUD), the mechanism of which remains unclear. In this study, network pharmacology and molecular docking were employed to predict the mechanism of Houpo in the treatment of PUD. Through literature review and TCMSP screening, 15 main active ingredients were obtained. The SwissTargetPrediction database was used to predict the potential targets of the ingredients, and Therapeutic Target Database(TTD), DrugBank, and Human Phenotype Ontology(HPO) to screen the disease-related targets. A total of 49 potential targets were obtained by the intersection of active ingre-dients-related targets and disease-related targets. Cytoscape 3.6.1 was employed to construct the protein-protein interaction network for the targets with high confidence(score>0.700) screened out by STRING. The DAVID database was used for GO and KEGG pathway enrichment of potential targets. GO enrichment analysis showed that the treatment mechanism was mostly related to nuclear receptor activity, ligand-activated transcription factor activity, and G protein-coupled acetylcholine receptor activity. KEGG enrichment analysis found that Houpo could regulate material metabolism, endocrine system, p53 signaling pathway, and PPAR signaling pathway. Molecu-lar docking verified that all 15 ingredients had good binding activities with key targets(CHRM1, CHRM2, FABP1, mTOR, and STAT3). The results mean that Houpo can treat PUD by participating in cell metabolism, inhibiting inflammatory cytokines, and regulating cell proliferation and apoptosis.
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Humans , Drugs, Chinese Herbal , Molecular Docking Simulation , Peptic Ulcer , Protein Interaction Maps , Receptor, Muscarinic M1 , Signal TransductionABSTRACT
Objective:To explore management experience for post-adolescent postoperative urethral stricture of hypospadias in a single center.Methods:The clinical data of 71 cases of postoperative urethral stricture of post-adolescent hypospadias from January 2015 to December 2019 were retrospectively analyzed. The average age was 27.7(12-65) years. The mean duration of urethral stricture was 33.4(1-240) months. The number of prior surgeries was 2.5(1-9). There were 32 cases of ectopic urethral orifice, including 22 on penile, 8 on scrotum and 2 on perineum. There were 17 cases of urethral stricture with penile curvature, 11 with urethra-cutaneous fistula, 9 with urethral diverticulum, 11 with urethral calculus and 25 with urethral infection. Ten patients kept suprapubic tubes; 61 patients were able to urinate on their own, but suffered from dysuria and weak steam. The average maximum uroflow rate of 71 cases was 4.7(0-11.2) ml/s. The primary urethral reconstruction procedures were performed on 33 cases, included 11 penile or scrotal septum flap urethroplasty, 2 urethral diverticulum wall flap urethroplasty, 12 oral mucosal urethroplasty and 8 urethrotomy. Thirty-three cases underwent two-staged surgery. For patients with penile curvature greater than 30 degrees, the penis was straightened with a urethrotomy in first stage. Besides, the dorsal skin of penis or oral mucosal graft were transferred to the ventral side of the penis to the preset urethral plate. In second-stage, Denis Brown urethroplasty was performed on 23 patients, tubularized incised plate (Snodgrass) urethroplasty on 6, and oral mucosa inlay urethral plate (Snodgraft) urethroplasty on 4. In 5 cases, preplacing of oral mucosa was done in the second stage with a third-staged urethroplasty. Penile curvature was relieved by ventral scar resection with the folding the dorsal tunica albuginea of corpus cavernosum when necessary.Results:The mean follow-up time was 30.5(4-59) months. Sixty-one patients got satisfying postoperative urination, with an average maximum uroflow rate of 22.7 ml/s (15.8-37.2 ml/s). Restenosis occurred in 10 cases, and urethral fistula in 7 cases. Re-stricture patients underwent urethrotomy in 5 cases, augmented urethroplasty with flap in 4 cases, and urethroplasty with oral mucosal graft in 1 case. Among the 7 patients with urethral fistula, 5 were cured by one fistula repair, and 1 cured by second repair; the rest one was left untreated. 2 patients still had penile curvature after operation.Conclusions:It is difficult to manage post-adolescent postoperative urethral stricture of hypospadias, especially for patients with residual penile curvature greater than 30 degrees and lack of penile skin. Performing correction of the curvature and reconstruction of the urethral plate in first stage and Denis Brown urethroplasty or Snodgrass urethroplasty in second or third stage could achieve good results.
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Objective:To investigate the efficacy and feasibility of urethroplasty using inner prepuce graft combined with Orandi flap for the treatment of the obliterated penile urethral atresic stricture.Methods:From January 2016 to September 2019, the clinical data of 18 obliterated penile urethral stricture cases were analyzed retrospectively. All the patients were treated using inner prepuce flap combined with Orandi Flap. The average age of the patients was 62.1 years old (range 20-81 years old). Ten cases had suprapubic cystostomy before operation. The maximum flow rate was 1.6-6.2 ml/s, with an average of 4.2ml/s. The intubation general anesthesia and lithotomy position was used. The foreskin of penis was incised longitudinally. The urethra was exposed and the segment of stricture was opened longitudinally. The range of stricture length was measured with soft ruler, ranging from 2.0 to 7.5 cm, with an average of 5.0cm. After the fibrotic tissue was completely removed, the dorsal inner prepuce was incised with needed length and width for harvesting a free skin flap in order to transplant and reconstruct the dorsal urethral. The Orandi flap was used to cover the ventral urethra, and a F14-16 silicone catheter was retained. The length range of the inner prepuce graft was 2.0-7.5 cm, with an average of 5.1cm; the width was 1.2-1.8 cm, with an average of 1.4cm. The length of Orandi flap was 2.2-7.7 cm, with an average of 6.0cm; the width was 1.0-1.5 cm, with an average of 1.3 cm. The catheter was removed 3-4 weeks after operation. The patients were then followed up after 3, 6 and 12 months postoperatively and then with annual assessments for the symptoms, urinary flow rate, and urethrography or soft urethroscopy when necessary.Results:All of the 18 operations were completed successfully. The patients were followed up for 6-36 months, with an average of 22 months. There were 5 patients with terminal dripping, 4 patients with recurrent urinary tract infection within half a year after operation, and antibiotic treatment being effective. The quality of life scores at 3 months and 6 months after operation were 0.8 (0-2) and 0.6 (0-1), respectively, which were statistically significant compared with before operation ( P<0.001). Conclusions:The use of free inner prepuce flap combined with Orandi flap is an effective treatment for the obliterated penile urethral atresic stricture, especially for the patients who are unwilling or unsuitable to harvest the oral mucosa. It has the advantages of convenient harvesting and less complications.
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Objective:To investigate the characteristics and the management of male genital lichen sclerosus (MGLSc)accompanied by urethral carcinoma.Methods:A retrospective analysis was performed on 16MGLSc accompanied by urethral carcinoma patients who were referred to Shanghai Sixth People’s Hospital between June 2000 and August 2019. The average age was 53.7 (45-69) years. All of the patients had a mean history of MGLSc 15(6-35) years, anterior urethral stricture received urethral dilatation and other inappropriate urethrotomy treatment for 10 (8-15) years. There were 5 cases of solid mass 4.5 (3-7) cm in scrotum, accompanied by obviously pain. There were 11 cases of infective masses 6(4-10)cm in the perineum, and the masses were ulcerated with purulent secretions and residue-like pus mixed with necrotic tissues draining from the wounds. Urethrocutaneous fistula developed in 9 cases, and the secretions in the fistula cannot heal. The diseased tissue was confirmed by pathology as the metastasis of invasive urothelial carcinoma in 12 patients and urethral squamous cell carcinoma in 4 patients. 9 cases of tumor invaded corpus spongiosum or corpus cavernosum, 5 cases invaded corpus spongiosum or corpus cavernosum, with enlarged firm one side inguinal node. 2 cases of tumor invaded corpus cavernosum, beyond prostatic capsule and bladder neck, bilateral palpable inguinal lymph nodes metastasis were found, one case found tumor involved the left testis. 9 cases were T 2-3N 0M 0, 5 cases T 2-3N 1M 0, 1 case T 3N 2M 0, 1 case T 4N 2M 1. 5 patients with substantial tumors located in the scrotum, penile-sparing scrotum tumor, urethral tumor resection and urethrostomy was performed in 2 patients. Partial phallectomy, urethral tumor resection and perineal urethrostomy were performed in 3 patients. 11 patients with urethral cancer complicated with perineal infectious mass, 2 patients underwent extensive resection of the tumor and suprapubic cystostomy. 8 cases with perineal tumor infection complicated with urethrocutaneous fistulas formation, of which 2 patients received perineal mass, urethral tumor, fistula resection and suprapubic cystostomy, 4 patients with unilateral inguinal lymph node metastasis and received perineal mass, urethral tumor, fistula, lymph node resection and suprapubic cystostomy. 2 patients with bilateral inguinal node metastasis underwent total phallectomy and urethrectomy, inguinal lymph node resection and suprapubic cystostomy. One case of perineal infectious mass with urethral cutaneous fistula and unilateral inguinal lymph node metastasis (T 2-3N 1M 0) gave up tumor resection. Results:The pathological examination of surgical resection of the glans and urethra showed typical MGLSc manifestations as epithelial keratinization, basal cell vacuoles degeneration, dermis lymphocyte infiltration. The pathological examination of the surgical excised diseased urethra and surrounding tumor tissue showed invasive urothelial carcinoma in 12 patients. Immunohistochemical staining showed positive expression of P53, Ki-67 and GATA3. 4 patients of urethral squamous carcinoma and immunohistochemical staining showed positive expression of Ki-67, P40 and GATA3. All patients received cisplatin combined with gemcitabine chemotherapy for an average of 4.8 (2-6)courses and received local radiotherapy (50-70Gy/5w). The mean postoperative survival time of the 16 patients was 26 (3-48) months, and the survival time of urethral transitional cell carcinoma and squamous cell carcinoma was 29 (18-48) months and 18 (3-24) months, respectively. All patients died of tumor metastasis, with 6 patients of lung metastsis, 2 patients of lumbar and bone metastasis, 3 patients of liver metastasis, 2 patients of brain metastasis and 3 patients of lung combined with bone metastasis.Conclusions:MGLSc can cause urethal stricture and urethral carcinoma. The clinical manifestations are dysuria, urinary tumor, repeated infection and urethral fistula. Tumor excision and urinary diversion are common surgical methods. Urethral transitional cell carcinoma and squamous cell carcinoma are common pathological types. Postoperative combined radiotherapy and chemotherapy can be used, but the overall prognosis is poor.
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Objective:To compare efficacy and erectile function outcome of Non-transecting Urethroplasty (NTU)with excision and primary anastomotic urethroplasty(EPA) in the management of bulbar urethral stricture.Method:A retrospective analysis of the case data of 73 patients with bulbar urethral stricture admitted to Shanghai Sixth People's Hospital from January 2016 to December 2019. The patients are 18 to 60 years old, because of the stenosis of the bulbous urethra, the length of the stenosis is less than 2 cm, and there is no history of urethral surgery, no multiple urethral stricture, and no obvious ED before surgery. According to the operation method, the patients were divided into 25 cases in NTU group and 48 cases in EPA group. The ages of the NTU group and the EPA group were (39.2±9.4) years and (42.1±9.3) years, respectively. The course of the disease was 6.0(3.0-14.0) months and 6.5(3.0-11.0) months, respectively, and the body mass index was (23.7±3.2) kg/m 2 and (24.5±2.7) kg/m 2, the preoperative maximum urine flow rate (Q max) was (8.7±4.3) ml/s and (7.9±4.6) ml/s, respectively, and the length of the stenosis was respectively (1.7±0.4) cm and (1.8±0.2) cm, the preoperative International Erectile Function Questionnaire (IIEF-5) was (20.9±1.9) points and (21.3±2.1) points, respectively, the difference was not statistically significant ( P>0.05). The etiology of NTU group and EPA group were 8 cases (32.0%) and 31 cases (64.6%) of trauma, 11 cases (44.0%) and 9 cases (18.8%) of iatrogenic injury, and 6 cases (24.0%) and 8 cases (16.7%), the difference was statistically significant ( P=0.023). All operations were performed by the same team of doctors. The urethral scar was assessed during the operation. If the scar tissue can be completely removed without breaking the urethra, NTU is performed. The distal end of the urethra is cut at the dorsal side of the narrow segment of the urethra, and the urethral scar is removed in a transverse wedge shape. The urethra is sutured; otherwise, EPA is performed, the urethra is completely cut off, the stricture of the urethra and surrounding scar tissue is completely removed, and the urethra end-to-end anastomosis is performed. Record the operation time and intraoperative bleeding. Difficulty urinating after surgery, urethral microscopy and urethral angiography showed that the urethral stricture at the surgical site was defined as a failure of the operation. The urinary catheter was removed 3 weeks after surgery, urine flow rate was measured at 3 weeks, 6 months, and 12 months after surgery, erectile function was evaluated 12 months after surgery, and urethral angiography was performed 1 to 2 years after surgery. Result:All 73 operations in this study were successfully completed. The operation time of NTU group and EPA group were (67.6±11.3) min and (62.7±10.1) min, respectively, and the difference was not statistically significant ( P=0.063); intraoperative blood loss was (71.6±16.2) ml and (86.0±20.8) ml, the difference was statistically significant ( P=0.004). The postoperative median follow-up time was 18.0 months (13-38 months). The surgical success rates of the NTU group and EPA group were 92.0%(23/25) and 93.8%(45/48), respectively. The Q max of the NTU group and the EPA group were (26.7±3.6) ml/s and (28.1±8.7) ml/s, (25.2±3.5) ml/s and (26.7±8.1) ml/s, (25.0±4.3) ml/s and (26.2±7.2) ml/s; the IIEF-5 scores were (21.8±1.6) and (20.6±2.9) points respectively at 12 months after operation, the difference was both No statistical significance ( P>0.05). There was a statistically significant difference in IIEF-5 between NTU group and preoperative ( P=0.023). Conclusion:NTU can achieve the same outcomes as EPA in the management of bulbar urethral stricture. More importantly, the continuance of bulbar urethra is attained and avoiding rupture of bulbar cavernous artery, so as to protect the blood supply of penile and erectile function. NTU is a minimally invasive, feasible surgical method, which is advised for the patients with shorter stricture segment and fewer fibrosis.
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Objective@#To analysis the risk factors for stricture recurrence after excision and primary anastomotic urethroplasty(EPA).@*Methods@#209 urethral stricture cases managed with EPA were retrospectively studied from January 2017 to December 2018 in our center. Of all the patients, 183 cases were diagnosed as posterior urethral stricture and 26 cases were diagnosed as bulbar urethral stricture. Their age ranged from 5 to 78 years(mean 42.1 years). 25 cases(12.0%) were defined as the obesity, whose BMI was more than 28 kg/m2. 12 cases(5.7%) has the history of diabetes mellitus. 103 cases(49.3%) smoked at least three months before operation. 127 cases(60.8%) didn't have the history of dilation. 42 cases(20.1%)had the history of dilation once or twice. 40 cases (19.1%)had the history of dilation more than three times. The history of urethroplasty included once in 38 cases(18.2%)and more than twice in 8 cases(3.8%). The location of stricture included posterior urethral stricture in 183 cases and bulbar stricture in 26 cases. The history of stricture ranged from 1 to 360 months(mean 35.1 months). The stricture length was(3.19±0.65)cm. The causes including trauma in 190 cases, iatrogenic urethral injury in 12 cases, inflammatory in 2 cases and others in 5 cases. The standard of stricture recurrence were defined as the urination difficulty after removal of catheter and endoscopic or radiographic evidence of obstruction in the area of repair. Univariate and multivariate analysis were performed by the use of Cox′s proportional hazards regression model to identify the related factors for stricture recurrence.@*Result@#The following up period was ranged from 3 to 32 months(average 18.78 months). Recurrence occurred in 31 cases in the period of 1.0 to 18.0 months(average 5.34 months). Factors had statistical differences in univariate analysis including stricture period(HR=1.007, P<0.001), stricture length(HR=5.334, P<0.001), history of direct vision internal urethrotomy (DVIU)(HR=2.901, P=0.003), history of urethral dilation ≥3 times(HR=6.214, P<0.001), history of urethroplasty 1 time, ≥2 times(HR=4.175, P=0.001, HR=9.885, P<0.001), 3 months smoking before surgery(HR=2.605, P=0.016), suprapubic cystostomy(HR=0.231, P=0.006), inferior pubectomy(HR=6.603, P<0.001). In multivariate analysis stricture length(HR=4.911, P<0.001), history of urethroplasty 1 time, ≥2 times(HR=2.387, P=0.045, HR=3.688, P=0.015), 3 months smoking before surgery(HR=2.730, P=0.030)were independent risk factors.@*Conclusion@#The urethral stricture recurrence mainly occurred within 6 months after surgery. The length of stricture, history of urethroplasty and 3 months smoking before surgery were the independent risk factors for stricture recurrence.