In 1946, radioactive iodine 131 was first used for the treatment of differentiated thyroid cancer. However, the limitations of early nuclear medicine technology, the lack of specificity, the efficacy of nuclide therapy, and its adverse effects have limited its widespreadly clinical application. In recent years, scientists and clinicians have linked radioisotopes to targeted parts (tumor-specific small molecules, peptides, or antibodies) to develop safe and effective nuclear drugs. Ra-223, Lutathera (lutetium-177), and Pluvicto (¹⁷⁷Lu-PSMA-617) have been successfully used in clinical treatment. Radioligand therapy has gradually shown good efficacy in different tumors. This paper focuses on the current situation of the application of therapeutic radioligand drugs in advanced malignant tumors and the latest research results and treatment strategies to achieve more accurate and personalized treatment methods, thereby to improve the curative effect, and reduce adverse reactions.

Colorectal cancer (CRC) seriously threatens people's health and safety, with high incidence and mortality rates. Surgery combined with radiotherapy and chemotherapy is the main treatment method for CRC at present, but the results are unsatisfactory. The emergence of tumor immunotherapy has brought hope to patients with CRC. Immunotherapy based on immune checkpoint inhibitors provides benefits to some patients. In addition, emerging tumor vaccines and adoptive cell therapy have achieved significant results. This paper reviews the current status and progress of immunotherapy for CRC.

Objective:To compare the clinical efficacy of laparoscopic inguinal lymph node dissection(L-ILND)and open inguinal lymph node dissection(O-lLND)in the treatment of penile cancer after radical penile cancer surgery. Methods:The clinical outcomes of 63 patients who were diagnosed with penile cancer(TNM staging:T1_3,N0-3,M0)and received L-ILND(41 cases)or O-ILND(22 cases)after radical penile cancer surgery in Department of Urology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology from 2008 to 2020 were retrospectively studied.The primary endpoint of this study was overall survival,and the secondary endpoints were 5-year overall survival and 5-year cancer-specific survival.The different clinical characteristics were compared between the L-ILND group and O-ILND group.Univariate and multivariate logistic regression analysis was used to study the risk facotrs for postoperative wound complications.Kaplan-Meier method was used for prognosis analysis.COX regression analysis was used to investigate the factors for overall survival prediction. Results:Among the 63 penile cancer patients studied,41 patients received L-ILND and the remaining 22 received O-ILND.There were no statistically significant differences in the baseline characteristics between the two groups of patients.The median overall survival(78 months vs 72 months,P=0.844),5-year overall survival rate(74.5％vs 78.3％,P=0.144),5-year cancer-specific survival rate(77.2％vs 71.4％,P=0.228)showed no obvious difference between L-ILND and O-ILND group.The rate of postoperative wound complications in the O-ILND group was significantly higher than that in the L-ILND group(74％vs 15％,P=0.01 2).The result of multivariate COX regression analysis showed that tumor grade[hazard ratio(H-R)=2.774,P=0.021]and lymph node pathological stage(HR=1.482,P=0.024)were significantly correlated with patients'prognosis. Conclusion:The clinical efficacy of L-ILND and O-ILND is similar,but L-ILND has a higher safety profile and lower incidence of postoperative wound complications.Therefore,L-ILND is a more ideal surgical approach for inguinal lymph node dissection after radical penile cancer surgery.

Objective To explore the correlation of the pan-immune-inflammation value (PIV) and the prognosis of patients with resectable colorectal cancer (CRC) and establish a predictive model. Methods A total of 753 patients who underwent primary lesion resection and were pathologically diagnosed with CRC were enrolled. They were randomly divided into training (n=527) and test (n=226) cohorts. The best cutoff value of PIV was determined by the time-dependent receiver operator characteristics curve, and patients were divided into high- and low-level groups to analyze the relationship between the high- and low-level groups of PIV and the clinicopathological characteristics and survival of patients. Chi-square test, Kaplan-Meier survival analysis, and Cox regression analysis were used to evaluate the prognosis. The accuracy of the model was evaluated by C index and Brier score. Results In the univariate model of overall survival (OS), high (> 231) baseline PIV (HR=1.627; 95%CI: 1.155-2.292, P=0.005) suggested that PIV level might be an independent prognostic factor for OS. The nomogram plotted according to PIV had a C index of 0.823. Its calibration curve showed good agreement between predicted and observed outcomes for one- and three-year OS probabilities, with Brier score of 0.035 and 0.068 for OS, respectively. Conclusion PIV can be used as a prognostic marker in patients with resectable CRC, and a novel prognostic model to guide clinical decision-making in CRC is successfully established.

Objective To assess the worldwide research status and the development trend of colorectal cancer. Methods Based on the papers of colorectal cancer indexed in SCI-E database from 2000 to 2019, the year of publication, countries, institutes, sources of journals, discipline fields, highly cited papers in ESI and research hotspots were analyzed by the bibliometric method. Results A total of 160183 papers on colorectal cancer were retrieved, and the number of papers increased year by year. The top 10 countries were USA, China, Japan, Germany, the United Kingdom, Italy, South Korea, France, Netherlands and Canada. Harvard University in the USA had a significant advantage on the research of colorectal cancer. The rank of the journals, institutes and highly cited papers were absolutely dominated by USA. Global research activities on the colorectal cancer displayed the characteristics of interdisciplinary development. The research hotspots mainly focus on the gut microbiota, genetic testing, targeted therapy, immunotherapy and so on. Conclusion It is necessary to strengthen the close combination of basic research and clinical application, and carry out colorectal cancer research in interdisciplinary collaboration with clinical problems.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective: To investigate treatment option of inguinal lymph node metastasis after inguinal lymph node dissection in patients with penile cancer. Methods: To retrospectively analyze the efficacy and prognostic factors of cisplatin combined with fluorouracil in the concurrent chemoradiotherapy of inguinal lymph node metastasis after penile cancer surgery. Twenty-three patients with inguinal lymph node metastasis after inguinal lymph node dissection for penile squamous cell carcinoma from February 2009 to December 2015 were included.Inguinal lymph node metastasis with squamous cell carcinoma were confirmed by pathology or cytology. Metastatic lymph nodes of each patient were fixed, not less than 2, and greater than 4 cm in diameter. All patients received concurrent chemoradiotherapy with cisplatin and 5-fluorouracil.The response rate was evaluated after radiotherapy. The local control rate, survival time and the prognostic factors were also analyzed. Results: The median time of postoperative inguinal lymph node metastasis was 6.1 months, and the recurrence rate of the patients within 16 months after the operation was 95%.The response rate was 65.2% (15/23). After treatment, the local pain was significantly relieved and 7 cases of local hemorrhage was relieved. The 1-, 2-year survival rates were 21.3% and 5.5%, respectively, with a median survival of 6.3 months(95% CI: 3.4-8.1). And local tumor response rate correlated with radiation dose. Cox multivariate analysis showed that N staging and histological grade were independent prognostic factors for survival after treatment. Conclusions Concurrent chemoradiotherapy is effective for postoperative inguinal lymph node metastasis, especially for the local recurrence with symptoms and for patients who are not suitable for surgical salvage regarding the local tumor control, pain relief and tumor hemorrhage. However, the overall survival rate of the patients who received treatment was still low. Lower extremity edema is the main complication of concurrent chemoradiotherapy. N staging and poor differentiation of the tissue are unfavorable prognostic factors.

Objective To investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

We aimed to express and purify three rabies virus glycoproteins with different tags and sizes. After analyzing their binding function, we wish to obtain a rabies virus glycoprotein with higher affinity and ability to specifically bind memory B cells. Experiments were carried out to express full length, as well as the ectodomain RVG by gene engineering method. Combined with the antibody of CD19 and CD27, the candidate protein labeling with fluorescence was used to analyze its binding function. Flow cytometry was used to detect the anti-rabies virus specific memory B cells in PBMCs, and confirm the binding ability between the candidate proteins and anti-rabies virus-specific memory B cells. We successfully constructed three expression vectors pGEX-5X-1-RVG, pET28a-RVG and pET30a-G. Three glycoproteins GST-RVG, His-RVG and His-G were obtained by optimized expression and purification conditions. The antigen specificity of purified GST-RVG, His-RVG and His-G were identified by Western blotting and ELISA. The affinity of these three purified glycoproteins to anti-rabies virus antibody were detected by competitive ELISA. Anti-rabies virus specific memory B cells in positive PBMCs gained from people who had ever been injected with the vaccine can be detected by flow cytometry. Thus, we got a recombinant rabies virus glycoprotein that had high-affinity and could sort antigen specific memory B cells.

Objective To establish reference values for blood pressure in cynomolgus monkeys in different ages.Methods The blood pressures and blood lipids indexes were detected in 521 cynomolgus monkeys using an American BECKMAN-CX4 automatic biochemical analyzer and a wrist electronic blood pressure monitor.Statistical tests were performed to analyze the data.Results Significant differences were found in blood pressure values of cynomolgus monkeys in different ages.Blood pressure values in the elderly group were higher than those of other groups.The morbidity of hypertension in the elderly group was higher than those of the other groups.Body mass index (BMI) in the hypertension group was higher than that of normal group in the same age.The incidence of hypertension in the elderly group with hyperlipemia was higher than that of other groups.Logistic regression analysis showed that age, BMI and hyperlipidemia in the hypertensive group were 1.435, 1.218, and 2.337 times higher than those of the normal group when predicting the risk of hypertension.Conclusions We have initially established reference values of blood pressure in cynomolgus monkeys in different ages.Age, BMI and hyperlipidemia are risk factors of spontaneous hypertension in cynomolgus monkeys, and the measurement of blood pressure may provide a basis for the screening of cynomolgus monkey model of spontaneous hypertensive and related research.