Objective To evaluate the safety and efficacy of sorafenib as first line treatment in patients with metastatic renal cell carcinoma. Methods Eleven patients with metastatic renal cell carcinoma after radical nephrectomy and 1 patient with locally advanced renal cell carcinoma and unre-sectable primary renal tumor were eligible for this study. The regimen was oral intake of sorafenib (400 mg twice daily) until the disease progression or toxicity becoming intolerable. Results All pa-tients were evaluable for response and toxicity assessment. The overall objective response rate and dis-ease control rate were 25%(3/12) and 83%(10/12, 3 partial responses and 7 disease stabilizations). The actuarial 6-month progression-free survival was 83% (10/12), while the median survival time was 16 months. The most common adverse effects included hand-foot skin reaction, rash, alopecia and hy-pertension. Conclusion Sorafenib is effective and safe as first line treatment for patients with meta-static renal cell carcinoma.

Objective To identify the relationship between sorafenib's efficacy and its side effects in treatment of advanced renal cell carcinoma patients. Methods Fifty-one patients having measurable diseases were diagnosed with advanced renal cell carcinoma. Of whom, 26 patients were in stage T1Nx,0,1M1, 12 patients in stage T2Nx,0 M1, 8 patients in stage T3NxM1, 5 patients in stage T4NxM1. These 46 patients of T1 -T3 had their primary diseases removed, but the 5 T~ patients didn"t have their primary diseases removed. These 51 patients received oral sorafenib 400 mg Bid continual-ly and they had CT scan every two months to evaluate the progression. The dosage of sorafenib wasmodified according to efficacy and toxicity. Two patients changed the dosage to 200 mg Bid due to se-vere side effects. Sixteen patients increased the dosage to 600 mg Bid or 800 mg Bid. The response ofSorafenib and toxicities as well as their severity were recorded. The toxicity severity was graded ac-cording to National Cancer Institute Common Toxicity Criteria version 3.0. The efficacy was deter-mined by RECIST criteria. The efficacy and progression free survival (PFS) were recorded. The sta-tistics analysis was conducted between sorafenib's side effects and efficacy as well as their severity by multi-faetor Logistic regression. Results The rates of adverse events in the patients receiving oral sorafenib were hand-foot skin reaetion 68. 6% (35/51), diarrhea 39. 2% (20/51), rash 25. 5% (13/ 51), mucositis 23.5% (12/51), hypertension 17.6% (9/51), and myelosuppression 13. 7%(7/51). The response rate in the patients who had toxicity of grade 3-4 was 33.3%(12/36), and that in the patients who had slight toxicity was 12.0%(3/25). The rate of hand-foot skin reaction was higher than that of diarrhea, rash, mucositis, hypertension and bone marrow suppression (P<0.01). Sor-afenib's efficacy was eorrelated to rash and mueositis (P=0.048, 0.045 respectively). More grade 3 4 side effects occurred in the patients who would have better response to sorafenib (P=0.008). The median PFS was 15.0 months and PFS was not related to the toxicity and its severity. Conclusions It may help to predict the response for sorafenib's side effects and efficacy in the treatment of the patients with advaneed renal cell earcinoma.

Objective To analyze the effect and related factors of sorafenib in the treatment of metastatic renal cell carcinoma(MRCC), and identify the potential predictive factors of sorafenib re-sponse. Methods The data of 51 MRCC patients who received sorafenib therapy, with or without combination with interferon or chemotherapy were retrospectively reviewed. After two cycles of treat-ment, patients were evaluated for progression or response. Pearson Chi-square test and Logistic re-gression test were performed respectively as univariate and multivariate analyses of sorafenib response. Results The overall objective response rate was 29.4%(95% confidence interval 16.9% to 41.9%, with 1(2.0%) complete response and 14(27.4%) partial responses. Twenty-nine(56.9%) had stable disease, and 7 (13.7%) had progression disease (PD). Significant independent predictive factors asso-ciated with good response in multivariate analysis were lung metastasis only(P=0.021, HR=5.127). Conclusions Sorafenib is effective in MRCC patients. Lung metastasis only is predictive factor in mul-tivariate analysis for sorafenib response.

Objective To evaluate the efficacy and safety of sunitinib as first line treatment in patients with metastatic renal cell carcinoma (RCC). Methods This study included 46 Chinese patients who were diagnosed with metastatic RCC after radical nephrectomy. The patients received oral sunitinib (50 mg once daily on a 4 weeks on, 2 weeks off) on a 6 weeks cycle dose schedule until disease progression or intolerable toxicities occurred. Results The overall objective response rate was 32.6% (95% confidence interval [CI, 19.1% to 46. 1%]), and the disease control rate was 86.9%,with complete response (CR) 0 (0%), partial responses (PRs) 15 (32.6%), stable disease (SD) 25(54.3 %), and progression disease (PD) 6 ( 13. 1%). The median progression-free survival was 11 months, and the 1-year survival rate was 65.2%, while the median overall survival (mOS) has not been reached. The main adverse events included fatigue 33 (71.7%), skin discoloration 29 (63.0 %),anorexia 28 (60.9%), hand-foot syndrome 26 (56.5%), oral mucositis 25 (54.3%), hypertension 19 (41.3%), facial edema 18 (39.1%), diarrhea 17 (37.0%), hemorrhage 17 (37.0%), nausea 15 (32.6%), and hematological toxicity: leukopenia 32 (69.6%), neutropenia 30 (65.2%), thrombocytopenia 28 (60.9%), anemia 21 (45.7%). Most of grade 3/4 serious adverse events were thrombocytopenia in 15 (32. 6%) patients. Conclusions Sunitinib has a prominent effect in metastatic renal cell cancer in a Chinese population with mostly mild to moderate adverse reactions. More attention should be paid to grade 3/4 adverse reaction of thrombocytopenia.

Objective To study the effects of.breathing booster training and aerosol inhalation with terbutaline and ambroxol on pulmonary function in postoperative lung cancer patients. Methods A total of 84 patients requiring resection operations for lung cancer were randomly divided into treatment and control groups.In the peri-operative period,breathing booster training and terbutaline and ambroxol aerosol inhalation were given to the treatment group,while only aerosol inhalation was given to the control group.Therapeutic effects were evaluated according to patients pulmonary function and postoperative complications 2 weeks and 1 day before the operation,and again 2 weeks after the operation.Postoperative quality of life (QOL) was evaluated with St.George's respiratory questionnaire (SGRQ) 1 month after the operation. Results There was no statistically significant difference in average pulmonary function between the two groups 2 weeks before the operation.Two weeks after the operation,pulmonary function had decreased in both groups,but it was significantly better in the treatment group than in the control group.The treatment group also had significantly fewer pulmonary complications.The QOL of patients in the treatment group had improved significantly 1 month after the operation. Conclusion Breathing booster training and inhalation of terbutaline and ambroxol aerosol during the peri-operative period can significantly improve pulmonary function,reduce respiratory complications and improve the QOL of patients requiring lung cancer resection operations.This is most important for promoting their early recovery.

Objective To evaluate the feasibility and effectiveness of the application of IQQA (Intelligent/interactive Qualitative and Quantitative Analysis) three-dimensional reconstruction technique in precise laparoscopic or robot-assisted laparoscopic partial nephrectomy (LPN or RAPN) for renal hilar tumors.Methods The study retrospectively reviewed 11patients with hilar tunors from February 2016 to February 2017.Of the 11 patients,4 were women and 7 were men,with an average age of 51 years (range 38 to 70 years).The average tumor size was 3.1 cm (range 1.7 to 4.3 cm).For tumor stage,9 patients were in T1a stage and 2 patients were in T1b stage.Tbe average R.E.N.A.L score was 8.7 (range 7 to 10).The mean preoperative GFR was 40.6 ml/min (range 32 to 45 ml/min).IQQA three-dimensional reconstruction technique was applied for the purpose of precise navigation and resection of the tumors.Multivariate analysis was used to identify predictors of warm ischemia time,estimated blood loss,major perioperative complications,and postoperative renal function.Results All 11 laparoscopic or robot-assisted laparoscopic hilar partial nephrectomies were successfully completed without conversion to a hand-assisted or an open approach.Under the navigation of IQQA,all tumors were found precisely at the first time during surgeries.The final pathologic examination revealed that all the 11 patients were clear cell renal cell carcinomas.The mean operative time was 142 minutes (range 90 to 230 minutes),with a mean warm ischemia time of 24 minutes (range 17 to 33 minutes).The estinated blood loss was 146 ml (range 50 to 400 ml).No intraoperative complications occurred.Two patients suffered from postoperative complications.One patient with gross hematuria was recovered by consistent bladder irrigation.The other patient with postoperative hemorrhage needed transfusion.All patients had negative margins on the final pathologic examination.At a mean follow-up period of 3 months,the mean GRR is 22.5 ml/min (range 13 to 34 ml/min) without any disease recurrence.Conclusions With peculiar features,such as accurate location,complete resection and fewer perioperative complications,the application of IQQA three-dimensional reconstruction technique in precise partial nephrectomy represents a safe and effective procedure for hilar tumors.

Objective: To investigate the clinical characteristics, treatment methods, and prognosis of metastatic papillary renal cell car-cinoma (pRCC). Methods: The clinical data of metastatic pRCC patients treated at the Department of Kidney Cancer and Melanoma, Pe-king University Cancer Hospital, were retrospectively analyzed. The prognosis of these patients was stratified through international metastatic renal cell carcinoma database consortium (IMDC) model. Survival and influencing factors were further analyzed using the Kaplan-Meier method and Cox proportional risk regression model. Results: From January 2003 to March 2018, 93 patients (median age, 50.0 years) were diagnosed with metastatic pRCC: 89 (95.7%) typeⅡcases and 4 (4.3%) typeⅠcases. The median follow-up dura-tion was 23.1 months, with 90, 44, and 14 patients having received first-line, second-line, and third-line treatments, respectively. The median overall survival (OS) of the 93 patients was (31.5±5.9) months [95% confidence interval (CI): 19.9-43.1], while the median OS of patients with low-, intermediate-, and high-risk (classified as per the International Metastatic Renal Cell Carcinoma Database Con-sortium [IMDC]) were (100.0±32.8), (38.3±8.2), and (16.4±1.2) months, respectively (high-risk vs. low/intermediate-risk, P<0.001; low-risk vs. intermediate-risk, P=0.015). The median progression free survival (PFS) with first-line treatment was (6.6±0.5) months. And the median PFS of the corresponding three groups stratified by IMDC score were (17.5±5.7), (7.1±2.3), and (5.2±1.5) months, respectively (high-risk vs . low-risk, P=0.002; high-risk vs . intermediate-risk, P=0.01). Conclusions: Metastatic pRCC is noted to have unique biologi-cal characteristics. The IMDC model can be used to predict the efficacy of first-line treatment using tyrosine kinase inhibitors as well as the prognosis of metastatic papillary renal cell carcinoma in such patients.

Objective To explore the role of Adra1a in regulating the LPS-induced inflammation response in primary hepatocytes of lipopolysaccharide-binding protein knockout(Lbp-/-)mice.Methods Primary hepatocytes were extracted from WT and Lbp-/-mice using a two-step perfusion method,and an inflammation model was established using LPS induction.Expression of Adra1a in primary hepatocytes of Lbp-/-mice was suppressed by administering the inhibitor prazosin and transfection with si-Adra1a.The cells were divided into three groups under inhibitor conditions:control group A,LPS group A,and prazosin group.For siRNA transfection,cells were also divided into groups:control group B,LPS group B,si-NC group,and si-Adra1a group.WT primary hepatocytes were divided into two groups:control group(blank)and LPS group(12 h stimulation).Changes in the Adra1a response to LPS stimulation were verified by Western blot.Other method ologies,such as CCK-8,qRT-PCR,and Western blot assays,were used to confirm improvements in cell inflammation and the survival rate by prazosin and si-Adra1a.Results Significant elevation in Adra1a protein expression in Lbp-/-primary hepatocytes was observed post-LPS stimulation(P＜0.01),whereas no notable change was found in the wildtype.A remarkable increase in the cell survival rate was noted in prazosin and si-Adra1a groups(P＜0.01,P＜0.05).Furthermore,prazosin and si-Adra1a groups exhibited significantly reduced expression of proinflammatory factors TNF-αand IL-1 β(P＜O.01),p-p38,p-ERK,and p-JNK(P＜0.01),which are associated with cell damage and inflammation.Conclusions Following LPS stimulation,upregulation of Adra1a and proinflammatory cytokine expression was observed in Lbp-/-primary hepatocytes.Specific downregulation of Adra1a expression using prazosin and si-Adra1a significantly decreased LPS-induced proinflammatory cytokines in Lbp-/-primary hepatocytes.Adra1a is implicated in the regulation of the LPS-induced inflammation response in primary hepatocytes of Lbp-/-mice.

Objective:To explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.

Objective To investigate the efficacy and safety of sunitinib as first-line therapy for metastatic renal cell carcinoma ( mRCC) on a 2 weeks on/1 week off intermittent dosing schedule.Methods A total of 11 mRCC patients were enrolled to receive sunitinib 50 mg/day in 2 weeks on/1 week off schedule per 6 weeks till disease progression or intolerable toxicity occurred.The primary end point was progression free survival ( PFS) , the secondary end points were overall survival ( OS) , incidence of adverse effects and objective response.Results The objective response rate in the 11 cases was 45.5%and disease control rate 72.7%( partial response n=5, stable disease n=3) .Till the last follow up on Dec 2013, the median PFS was 17.0 months (95%CI 7.3 to 26.7 months), and median OS 26.0 months (95%CI 2.2 to 49.8 months). The common adverse events included leucopenia, thrombocytopenia, diarrhea, mucositis and hand-foot skin reaction.Dose reduction to 37.5 mg was seen only in 2 patients without discontinuation. Conclusions Sunitinib on an intermittent dosing schedule 2 weeks on /1 week off as first-line therapy for mRCC patients shows a good efficacy and tolerance, with less grade 3-4 drug-related toxicities and a tendency of prolonged PFS in mRCC patients.