OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

【Objective】 To systematically evaluate the efficacy and safety of targeted drugs in the treatment of metastatic non-clear cell renal cell carcinoma (nccRCC) and to provide guidance for clinical treatment. 【Methods】 All observational studies and randomized controlled trials (RCTs) of nccRCC treated with targeted drugs were retrieved from the PubMed, Embase, the Cochrane Library and Web of Science. Three independent investigators screened the literature, extracted data and evaluated the quality of literature. The RCTs were evaluated using the Cochrane Handbook. One research with insufficient outcome data (follow-up bias) was assessed as high risk, and the other studies showed low or uncertain risk. The non-RCTs were evaluated with the JBI Quality Assessment Tool, and all studies displayed a low risk of bias. The data were analyzed with Stata 17.0 software. 【Results】 A total of 16 studies involving 989 patients were included. Meta-analysis showed that the objective response rate (ORR) was 12.6% (95%CI:8.1%-17.9%), the total disease control rate (DCR) was 65.3% (95%CI:58.3%-72.1%), the total median progression-free survival (PFS) was 5.80 (95%CI:4.69-6.91) months, and the median overall survival (OS) was 15.93 (95%CI:12.17-19.68) months. In subgroup analysis, the total ORR of patients with metastatic nccRCC treated with sunitinib and cabozantinib were 11.7% (95%CI:6.5%-18.0%) and 17.2% (95%CI:8.4%-28.2%), respectively. The total ORR of patients with papillary renal cell carcinoma was 9.1% (95%CI:2.4%-18.9%). 【Conclusion】 Targeted drugs have a significant effect on patients with metastatic nccRCC, but adverse reactions may occur. Targeted drugs have poor effects on metastatic papillary renal cell carcinoma, and cabozantinib may have greater survival benefits.

Objective:To construct an effective survival nomogram for patients with clear cell renal cell carcinoma (ccRCC) using a large sample sized Chinese dataset, which can be used to predict individual 3- and 5-year overall survival (OS) precisely.Methods:The data of 672 ccRCC patients received operation diagnosed at Xijing Hospital from January 2012 to December 2016 were retrospectively analyzed. There were 467 males and 205 females. Their median age was 56 years old (ranging 23-83 years old). There were 327 patients with tumor on the left kidney and 345 patients with tumor on the right kidney. Clinical stageⅠ, Ⅱ, Ⅲ, Ⅳ were 584, 47, 19 and 22 cases, respectively. At the time of diagnosis, 504 patients were asymptomatic and 168 patients were symptomatic. Preoperative alkaline phosphatase was 80 (41-240) U/L. Preoperative serum albumin was 44.8 (30.5-59.8) g/L. Preoperative neutrophil absolute value/lymphocyte absolute value (NLR) was 2.25 (0.81-9.89). Preoperative platelet count was 205 (82-589)×10 9/L. Preoperative creatinine was 97 (55-230) μmol/L. Radical nephrectomy was performed in 420 (62.5%) patients and partial nephrectomy was performed in 252 patients. Cox multivariate analysis was used to determine the independent predictors of the postoperative OS. Then, the nomogram was constructed using R software, which integrates all independent predictors according to the coefficients in the multivariate analysis. Moreover, the performance of the nomogram was evaluated using the consistency index (C-index) and the calibration plots. Results:Cox multivariate analysis results showed that age at diagnosis ( P<0.001), clinical TNM stage ( P<0.001), preoperative NLR ( P=0.012), preoperative alkaline phosphatase ( P=0.002) and preoperative albumin ( P<0.001) were the independent predictors of postoperative OS in ccRCC patients. The nomogram established by integrating these five factors had a good discriminatory ability (C-index=0.819, 95% CI 0.813-0.825), and the calibration plots showed that excellent agreements between the nomogram prediction and the actual observation were achieved. Conclusions:Based on a large sample sized Chinese dataset, this study established an effective survival model for patients with ccRCC and good performance of the nomogram was demonstrated by internal validation. Our nomogram can help urologists to predict individual 3- and 5-year OS accurately for Chinese ccRCC patients.

Objective:To explore the prognostic factors of patients with gallbladder cancer in different anatomical locations.Methods:A retrospective analysis of the clinical data of 140 patients with gallbladder cancer who were surgically treated in the 904 Hospital of the Joint Logistics Support Force from January 2015 to December 2015. Among them, 49 were males and 91 were females, with a median age of 64.0 years. According to the location of gallbladder cancer, they were divided into the neck of the gallbladder and the bottom of the gallbladder. The clinical data of the two groups were compared. The Kaplan-Meier method was used for univariate analysis, and Cox multivariate regression analysis was used to analyze the significant factors of univariate survival to determine the independent risk factors that affect the prognosis of patients with gallbladder cancer. Use Pearson correlation to analyze the correlation between clinicopathological characteristics.Results:Patients in the neck of the gallbladder group had higher levels of preoperative total bilirubin, preoperative albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, extrahepatic bile duct resection (biliary-enteric anastomosis), radical resection, breakthrough of the liver/serous membrane invasion, lymph node metastasis, TNM staging, local recurrence in the operation area in the surgical area were statistically significant ( P<0.05). Univariate analysis suggested that preoperative jaundice, Glasgow prognostic score (GPS), C-reactive protein, carcinoembryonic antigen, carbohydrate antigen 19-9, accidental gallbladder cancer, surgical method, tumor pathological type, tumor differentiation degree, tumor growth location (neck than the bottom of the body) are related to the prognosis (all P<0.05). Cox regression analysis indicated that GPS ( RR=3.272, 95 CI: 1.987-5.388), surgical method ( RR=4.149, 95 CI: 2.561-6.723), tumor location ( RR=0.316, 95 CI: 0.209-0.478), distant metastasis ( RR=1.695, 95 CI: 1.036-2.775) and TNM staging ( RR=3.686, 95 CI: 2.222-6.115) are independent risk factors affecting the prognosis of gallbladder cancer. Correlation analysis suggests that neck tumors are related to later staging, liver bile duct invasion, lymph node metastasis, high inflammation levels, and low radical cure rates. Conclusions:Gallbladder cancer that occurs in the neck of the gallbladder is an independent factor influencing the poor prognosis of patients with surgical treatment. In addition, TNM staging, distant metastasis and Glasgow score are important predictors of survival in patients with gallbladder cancer.

Objective:To investigate the expression and clinical significance of Golgi phosphoprotein 3 (GOLPH3) and NOD-like receptor protein 3 (NLRP3) in gallbladder carcinoma (GBC).Methods:Surgical specimens and clinical data were collected from 63 patients with GBC who underwent radical cholecystectomy in the 904th Hospital of Joint Logistic Support Force of PLA from January 2014 to January 2019. In the GBC group, there were 21 males and 42 females, with an average age of 62.5 years. For 30 patients with mild to moderate atypical hyperplasia of gallbladder during the same period were included in the precancerous lesion group, including 9 males and 21 females, with an average age of 62.4 years. Normal gallbladder specimens from 20 patients who underwent surgical resection due to liver trauma or giant hepatic hemangioma were collected and included in the normal group, including 7 males and 13 females, with an average age of 61.9 years. The expressions of GOLPH3, NLRP3, Ki-67 were detected by immunohistochemistry. Log-rank test and Cox regression were adopted to analyze the GOLPH3 and NLRP3 expression and survival prognosis of gallbladder cancer patients.Results:Expression of GOLPH3 and NLRP3 in the tumor group, precancerous lesion group and normal group was decreased separately. In GBC tissues, the level of GOLPH3 and NLRP3 was positively correlated with the Ki-67 expression ( r=0.972 and r=0.969, both P<0.05). Multivariate analysis showed that high level of GOLPH3 ( HR=4.891, 95% CI: 1.776-13.470) and NLRP3 ( HR=3.006, 95% CI: 1.273-7.099) was an independent risk factor for predicting the postoperative survival of patients with GBC (both P<0.05). Conclusion:GOLPH3 and NLRP3 are highly expressed in GBC tissues, and high expression of GOLPH3 and NLRP3 is an independent risk factor for postoperative survival in patients with GBC.

Objective: To explore the independent predictors for recurrence-free survival (RFS) in patients with papillary renal cell carcinoma (PRCC), and establish a nomogram to predict individual 2-year RFS. Methods: The data of patients diagnosed in Xijing Hospital of the Air Force Medical University from June 2009 to May 2018 were retrospectively analyzed. A total of 71 patients with primary T_1-4N₀M₀ unilateral tumor were included in this study. The median age was 54 (range from 25 to 83) years. There were 51 males and 20 females. There were 27 cases of typeⅠ, 44 cases of type Ⅱ, 36 cases of left tumor and 35 cases of right tumor. Patients with clinical Ⅰ, Ⅱ, Ⅲ, Ⅳ stage were 47 cases, 12 cases, 9 cases and 3 cases, respectively. Tumor necrosis occurred in 15 cases (21.1%). The average preoperative alkaline phosphatase (ALP) was 89.0(43.0-217.0) U/L, the average preoperative hemoglobin (Hb) was (132.5±19.9) g/L, with 20 cases (28.2%) of Hb<120 g/L before surgery; the average of preoperative Hb was (132.5±19.9) g/L, among which 20 cases (28.2%) had Hb<120 g/L before surgery; the average of preoperative neutrophils/lymphocytes (NLR) was 2.40 (1.03-6.77); radical nephrectomy was performed in 43 patients and nephrectomy was performed in 28 patients. The 1-, 2-, and 3-year RFS were calculated using Kaplan-Meier method and the differences among different subgroups were assessed using Log-rank test. Univariate and multivariate Cox regression analysis were used to identify the independent predictors for RFS, and the nomogram was developed using R software according to the results of multivariate Cox regression analysis. Furthermore, the predictive ability of the nomogram was internally validated using the Bootstrap method by calculating the C-index and drawing the calibration plot. Results: After a median follow-up of 41 ( range from 25 to 83) months, 16 (22.5%) recurrence occurred, including 4 local recurrence and 12 distant recurrence, and 11 (68.8%) patients relapsed within 2 years after surgery. The 1, 2, and 3-year RFS were 88.6%, 80.4%, and 78.7%, respectively. Clinical stage Ⅱ (HR=3.655, 95%CI 1.036-12.890, P=0.044) and stage ≥Ⅲ(HR=3.654, 95%CI 1.008-13.248, P=0.049), preoperative ALP≥90U/L(HR=3.274, 95%CI 1.044-10.267, P=0.042), preoperative Hb<120 g/L (HR=4.771, 95%CI 1.553-14.660, P=0.006), and preoperative NLR≥2.40(HR=4.701, 95%CI 1.238-17.849, P=0.023) were identified as independent risk factors for RFS. On internal validation, the nomogram which integrates the four predictors of clinical stage, preoperative ALP, preoperative HB and preoperative NLR, has a good predictive performance (C-index =0.829, 95%CI 0.819-0.839). Conclusions In the present study based on single center data, clinical stage Ⅱ and ≥Ⅲ, preoperative ALP≥90 U/L, preoperative Hb<120 g/L and preoperative NLR ≥2.40 were independent predictors for postoperative RFS in patients with PRCC, and a new preoperative nomogram for predicting individual postoperative 2-year RFS was established, which would be helpful for urologists to develop more systematic treatment plans.

Objective: To investigate the independent predictors of inguinal lymph node metastasis (LLM) in patients with penile squamous cell carcinoma (SCCP), and to establish a nomogram for predicting individual LLM risk. Methods: The data of patients with SCCP diagnosed at the department of urology, Xijing Hospital from July 2009 to June 2019 were analyzed retrospectively. A total of 101 patients were included in this study, with age of 55 (26-84) years. There were 25 (24.8%) and 76 (75.2%) patients with and without palpable inguinal lymph node enlargement, respectively. There were 47 cases (46.5%), 40 cases (39.6%) and 14 cases (13.9%) in T₁, T₂ and T₃ stages, respectively; there were 67 cases (66.3%), 21 cases (20.8%) and 13 cases (12.9%) in Broder 1, 2 and 3, respectively. The average value (or median) of fibrinogen was 2.84 (1.72-5.00)g/L; alkaline phosphatase was 80(32±214)U, hemoglobin was 147(81-180)g, platelet count was (193.74±65.68×10⁹/L, absolute value of neutrophils, monocytes and lymphocytes were 3.98(1.19-11.85)×10⁹/L, 0.44(0.17-1.90)×10⁹/L and 1.68(0.58-4.13)×10⁹/L, respectively. The average (or median) value of PLR, NLR and LMR were 113.38(18.80-418.42), 2.42(0.59-10.22) and 3.84 (1.08-9.89), respectively. There were 26 cases (25.7%) with LLM and 75 cases (74.3%) without LLM. The independent predictors of LLM were identified by univariate and multivariate logistic regression analyses. The R software was used to establish the nomogram by integrating all independent predictors, and the bootstrap method was used to internally validated our nomogram, where the value of AUC (area under the ROC curve) was calculated and the calibration plot was drawn. Results: Clinical inguinal lymph node status (P<0.006), T stage (P<0.021), Broder grade (P<0.017) and absolute neutrophil value (P<0.043) were independent predictors of LLM. The accuracy of our nomogram was 0.875 (AUC=0.875, 95%CI 0.859-0.891); Moreover, the risk of LLM predicted by nomogram was in good consistency with the actual LLM rate, and the errors of the nomogram-predicted LLM risks were all within 10%. Conclusions Clinical inguinal lymph node status, T stage, broder grade and absolute value of neutrophils were identified as independent predictors of LLM in patients with SCCP on the basis of single center data. A generic nomogram predicting LLM risk for Chinese patients was developed, which would be helpful to screen SCCP patients who need prophylactic inguinal lymph node dissection.

Objective: To explore the independent predictors for disease-specific survival (DSS) rate in patients with stage N_1-3 testicular seminoma (TS), and establish a nomogram to predict individual 5-year DSS. Methods: The data of N_1-3 TS patients registered in the SEER database of National Cancer Institute (USA) from January 2004 to December 2015 were retrospectively analyzed. The 5-year overall survival (OS) rate and DSS rate were calculated using Kaplan-Meier method and the differences among different subgroups were assessed using log-rank test. Besides, the independent predictors of DSS were defined using multivariate Cox regression analysis, and nomogram was drawn using R software. Furthermore, the predictive performance of the nomogram was internally validated using the C-index and calibration plot. Results: TNM stage ⅢA (HR=5.604, 95%CI: 1.252-25.083, P=0.024), ⅢB (HR=6.710, 95%CI: 1.923-23.410, P=0.003) and ⅢC (HR=13.189, 95%CI: 3.916-44.420, P<0.001), age at diagnosis ≥45 years old (HR=3.575, 95%CI: 2.014-6.344, P<0.001), and patients without spouse (HR=2.346, 95%CI: 1.406-3.914, P=0.001) were identified as independent risk factors for DSS. On internal validation, the predictive accuracy of our nomogram was 0.751 (C-index: 0.751, 95%CI: 0.694-0.808). Besides, the calibration plot showed that the predicted survival outcomes were highly consistent with the actual survival outcomes. Conclusion The study confirms that age at diagnosis ≥45 years old, TNM stage ≥ⅢA and patients without spouse are the independent risk factors for DSS in TS patients with stage N_1-3, and the nomogram for predicting individual 5-year DSS is established.

In order to provide reference for treatment of liver tumors using traditional Chinese medicine, we analyzed the research status of liver tumor treatment with traditional Chinese Medicine based on PubMed. By the bibliography information concurrence mining system (BICOMB 2013), the literature were collected and analyzed from PubMed database from the day of establishment to 31 October 2017. CytoScape3.6.1 software was used to draw the Co-occurrence analysis chart of high-frequency subject headings and the subheadings, and SPSS17 statistical software was used to cluster the high frequency subject headings. 365 literatures were collected in total. The amount of published articles is increasing year by year. The literatures were mainly in English. From the literature indicating the author's country, we found that 70％ of the top 10 countries and regions which published the most papers were from Asia. Among them, Chinese scholars ranked first. The top 5 of the high-frequency subject headings and the subheadings were Humans, Male, Animals, Liver Neoplasms/drug therapy and Carcinoma, and Hepatocellular/drug therapy. The research focused on the following 9 aspects: metabolism of liver cells, neoplasms, liver cancer pathology, pharmacological efficacy of liver cancer, relationship between cell proliferation and apoptosis and efficacy; xenograft model antitumor assays in mice, pharmacology of antitumor Chinese herbal medicine or phytogenic drugs, the effects of dose-response relationship, cellular activity and signal transduction on drug efficacy, therapeutic uses of traditional and phytotherapy and the outcome and mortality of liver tumor. By the bibliometric analysis in the field of traditional medicine for liver tumor, we can understand the research direction and development status of this field, which can be reference for prevention and treatment of liver cancer with TCM.

To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.
Cells, Cultured ; Dental Casting Technique ; Hepatocytes/drug effects* ; Humans ; Metal Nanoparticles/toxicity* ; Silver/toxicity* ; Toxicity Tests