Objective: To establish a method for simultaneous determination of calceolarioside B and chlorogenic acid in Caulis Stauntoniae Chinensis tablets by HPLC.
Methods: The analysis was performed on a Thermo BDS HYPERSIL C₁₈ column (4.6 mm×250 mm,5 μm) maintained at 35 ℃. The mobile phase was consisted of methanol and 0.1% phosphoric acid solution, and gradient eluted with a flow rate of 1.0 mL·min^-1. The detection wavelength was 327 nm, and the injection volume was 10 μL.
Results: The linear ranges of calceolarioside B and chlorogenic acid were 0.51-20.60 μg·mL^-1 (r=1.000) and 0.52-20.63 μg·mL^-1 (r=1.000), respectively. The average recoveries were 100.3% with RSD as 1.1% and 105.9% with RSD as 1.4%, respectively. The content results of 5 batches of Caulis Stauntoniae Chinensis tablets were 0.083-1.115 mg·g^-1 for calceolarioside B and 0.161-1.204 mg·g^-1 for chlorogenic acid.
Conclusion: The method can be used for improving the quality evaluation standard of Caulis Stauntoniae Chinensis tablets.

Objective To investigate the relationship between the treatment of EGFR-TKI icotinib and the prognosis of advanced lung adenocarcinoma patients with EGFR mutation. Methods Patients with advanced lung adenocarcinoma who had EGFR19 and 21 gene mutations and were treated with EGFR-TKI icotinib were enrolled. The relationships of clinical features, EGFR gene mutation subtypes, and different sites with patients'prognosis were analyzed. Results A total of 101 patients with advanced lung adenocarcinoma were included in this study, including 58 cases (57.4%) of EGFR gene exon 19 deletion mutation (EGFR Del19) and 43 cases (42.6%) of EGFR gene exon 21 point mutation (EGFR L858R). The objective response rate was 63.4%. The mPFS and mOS were 13 months and 27 months, respectively. In addition, the mPFS and mOS of EGFR Del19 and EGFR19 mutation 746-750 were higher than those of EGFR L858R and other EGFR mutations, respectively. Meanwhile, multivariate analysis showed that the number of metastatic sites and pleural metastasis were independent influencing factors of patients'OS (P=0.027; P=0.041). The mOS of patients with the number of metastatic sites ≤3 and without pleural metastasis were 29 and 27 months, respectively. Conclusion There is no significant difference found in overall survival of advanced lung adenocarcinoma patients treated with icotinib among different EGFR mutation subtypes and sites. Herein, the overall survival time is longer in patients with less than three metastatic sites and without pleural metastasis.

Online courses are an indispensable part of medical teaching in the new era. Online courses have good prospects, although also with certain problems in practice. As an important basic medical course, medical genetics has both basic theoretical knowledge and clinical cases, involving basic principles and the latest developments. A single online course or offline teaching model cannot meet the needs of subject development and training a new generation of medical professionals. Therefore, actively exploring the online and offline hybrid teaching model is one of the important topics in the current medical teaching reform.
Genetics, Medical

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.

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.

This paper was to investigate the effect of total flavonoids of Lichi Semen(TFL) on carbon tetrachloride(CCl_4)-induced liver fibrosis in rats, analyze and predict its mechanism of action and potential quality markers(Q-marker). Firstly, male SD rats were taken and injected subcutaneously with a 40% CCl_4-vegetable oil solution twice a week for 8 consecutive weeks to establish a rat model of liver fibrosis. The rats with liver fibrosis were randomly divided into model group, silybin group(43.19 mg·kg~(-1)), Fuzheng Huayu Capsules group(462.75 mg·kg~(-1)), and TFL groups(100 mg·kg~(-1) and 25 mg·kg~(-1)), with normal rats as a blank group, 10 rats in each group. Except for the blank group, the rats in the other groups were subcutaneously injected with 40% CCl_4-vegetable oil solution of a maintenance dose, once a week. The rats in various treatment groups received corresponding doses of drugs, while the rats in the blank group and model group received the same volume of normal saline once a day for 4 weeks. At the end of the experiment, blood was collected from the abdominal aorta and the liver tissues were collected. The levels of total bilirubin(TBiL), direct bilirubin(DBiL), indirect bilirubin(IBiL), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum were detected by using an automatic biochemical detector. Masson staining was used to observe the histopathological changes of rat liver. Then, the chemical compositions of TFL were collected, and the action targets of these chemical compositions were predicted through SWISS database and reverse molecular docking server(DRAR-CPI). After screening of disease targets of liver fibrosis by Gene Cards database, the protein-protein interaction was analyzed with use of STRING database, and GO(gene ontology) analysis and KEGG(Kyoto encyclopedia of genes and genomes) enrich analysis were also carried out. Moreover, an iTRAQ proteomics technology was used to determine protein expression in liver tissues of rats in TFL, model and blank groups to verify the targets. Furthermore, Cytoscape software was used to establish and visualize the network of chemical components, targets and pathways, and predict the potential Q-marker of TFL. The results showed that the levels of TBiL, DBiL, IBiL, ALT, and AST in the model group were significantly higher than those in the blank normal group(P<0.05), and the above levels in the treatment groups were lower than those in the model group, but with no significant differences. Masson staining showed that the liver damage and the degree of fibrosis were severe in the model group, and were relieved to different degrees in the treatment groups. Then, 74 chemical components were screened, which could act on 865 targets such as EGFR and SRC, participating in the regulation of cancer pathways, PI3 K-Akt signaling pathway, HIF-1 signaling pathway and other signaling pathways closely related to liver fibrosis. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin showed the highest correlation with liver fibrosis-related targets and pathways. Proteomics results showed that a total of 18 proteins among the 45 proteins predicted by internet pharmacology were identified, among which 6 proteins were significantly expressed, including 5 up-regulated proteins and 1 down-regulated protein. The protein expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1 was significantly returned to a normal state in the TFL treatment groups. In conclusion, TFL may demonstrate the anti-hepatic fibrosis and potential hepatoprotective effects by regulating the expression of ALB, PLG, HSP90 AA1, EGFR and MAP2 K1, which may be associated with the regulation of multiple signaling pathways related to liver fibrosis such as PI3 K-Akt pathway. Pinocembrin, quercetin, epicatechin, procyanidin A2, naringenin, nobiletin, phlorizin and rutin could be regarded as potential Q-markers of TFL for quality control.
Animals ; Carbon Tetrachloride ; Flavonoids ; Liver/pathology* ; Liver Cirrhosis ; Male ; Molecular Docking Simulation ; Rats ; Rats, Sprague-Dawley ; Semen

Objective:To study the clinical features, management methods, and survival of patients with urinary neuroendocrine carcinoma (NEC).Methods:A retrospective study of 22 patients with urinary NEC was performed from March 2008 to August 2019, including 21 male and 1 female. The average age was 68.2±9.9 years. Location of the lesion included left adrenal gland 1 case, right kidney 1 case, left ureter 1 case, bladder 9 cases and prostate 10 cases. 16 cases with bladder or prostate NECs had hematuria. Radiological feature was solid tumors with inhomogeneous enhancement and obvious local invasion. Clinical TNM stages included left adrenal NEC(T 2N 0M 0), right kidney(T 4N 1M 0), left ureter(T 3N 1M 0), bladder(2 cases with T 2N 0M 0, 2 with T 3N 0M 0, 3 with T 3N 1M 0, 1 with T 4N 2M 0 and 1 with T 4N 1M 1), prostate(2 cases with T 2N 0M 0, 2 with T 3N 0M 0, 1 with T 4N 0M 0, 2 with T 4N 0M 1 and 3 with T 4N 1M 1). Radical surgery was performed for 8 patients (5 with bladder NECs, 1 for renal, ureter and prostate NECs respectively). Tumor resection was performed for left adrenal NEC. 4 bladder NECs and 3 prostate NECs were managed with palliative resections and 4 prostate NECs with conservative treatment, 2 prostate NECs lost to follow up after needle biopsy. Results:Pathological results were as follows, 12 cases with primary SCNECs, 2 cases with NECs, 3 cases were bladder SCNECs combined with high grade urothelial carcinoma, 4 cases were prostate SCNECs combined with adenocarcinoma, 1 case was SCNEC combined with LCNEC. Pathological tests indicated that average Ki-67 was (60.9±16.0)%, synaptophysin(SYN)was positive in 20 cases, chromogranin A(CgA)in 10 cases and CD56 in 19 cases. The median following time was 15.5 months(8-108 months)of 20 patients, 16 were deceased, 3 were surviving with tumor and 1 with clinical cure. The 1-, 2- and 3-year overall survival rates between bladder NECs(66.7%, 22.2%, 11.1%)and NECs in other locations(90.9%, 63.6%, 42.4%) had statistical significance( P=0.038). Conclusions:Hematuria was the main symptom of bladder and prostate NEC. SCNEC is the most common pathological type, many were in advanced stage when diagnosed. Even though managed with radical surgery, most of cases had poor prognosis, overall survival rate of bladder NECs was lower than other locations. Radical surgery in early stage and multi-disciplinary therapy can improve the situation.

Methods:Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ 2 test or Fisher test. Results:No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ 2=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ 2=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ 2=4.029, P=0.045). OLH (95 % CI: 1.55 to 10.75, P=0.004) and postoperative complications (95 % CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95 % CI: 1.428 to 44.080, P=0.018) and residual stones (95 % CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95 % CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion:Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

Methods:Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ 2 test or Fisher test. Results:No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ 2=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ 2=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ 2=4.029, P=0.045). OLH (95 % CI: 1.55 to 10.75, P=0.004) and postoperative complications (95 % CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95 % CI: 1.428 to 44.080, P=0.018) and residual stones (95 % CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95 % CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion:Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

Objective To investigate the clinical effect of transverse island fasciocutaneous penile flap in the treatment of meatus and navicular fossa stricture.Methods Fifteen patients with urethral reconstruction with transverse island fasciocutaneous penile flap from October 2014 to December 2018 were enrolled.Six patients had a history of urethroscopic surgery,three had a history of lichensclerosus,three had a history of urethral dilation,and three had no obvious causes.All patients underwent transverse incision under the coronal sulcus,and after fully dissecting the urethra,the urethra was opened longitudinally ventrally.After measuring the actual length of stenosis,the irradiance fascia flap with the corresponding length of the incision was reconstructed.The patients were reviewed at 1 and 3 months after operation,and any complications such as recurrence or urinary fistula were recorded.The urine flow rate was tested 3 months after surgery.Results All 15 patients in this group underwent a successfully operation.The actual measurement of urethral stricture length was 0.5-4.0 cm during operation,with the average of 2.82 cm.Three months after the operation,the urine flow rate ranged from 13.5 ml/s to 23.7 ml/s,with an average of 18.5 ml/s.The overall successful rate was 93.3％ (14/15).The rate of post-operative fistula was 20.0％ (3/15).Two cases complained of needle-like fistula at the incision.One case healed after 3 months,and the other gave up further treatment.One patient developed urethral stricture and urethral skin spasm again 1 month later and was surgically repaired again.Conclusions The initial experience of pedicled island fascia flap for the treatment of urethral stenosis and scaphoid stenosis is safe,feasible and effective for the treatment of urethral stricture.