Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00～0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01～0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08～2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.

With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

Objective:To screen the factors influencing overall survival (OS) of patients undergoing radical resection for colorectal cancer (CRC) and to construct a prognostic model for OS of patients after CRC.Methods:The clinical data of 350 patients with stage Ⅰ-Ⅳ CRC who underwent radical resection in the People's Hospital of Wuhan University from March 2017 to December 2019 were collected retrospectively. Patients were divided into subgroups 0 ( n=70), 1 ( n=172), and 2 ( n=108) according to different preoperative systemic inflammation score (SIS). The relationship between different SIS, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), systemic immune inflammation index (SII) and prognosis of CRC patients undergoing radical surgical resection were analyzed, and Cox regression models were used to perform univariate and multifactorial analyses of factors affecting patient prognosis, and column line graph models were constructed based on the results of multifactorial analyses. Results:By the deadline of follow-up, 80 of 350 CRC patients died, and the 5-year OS rate was 77.14%. The 5-year survival rates of patients in SIS group 0, group 1 and group 2 were 95.71%, 79.65% and 61.11% respectively, with a statistically significant difference ( χ2=30.19, P<0.001). Statistically significant differences in age ( χ2=19.40, P<0.001), tumor site ( χ2=8.18, P=0.017), T stage ( χ2=10.01, P=0.007), TNM stage ( χ2=14.80, P=0.001), tumor diameter ( χ2=13.91, P=0.001) and carcino-embryonic antigen (CEA) level ( χ2=10.12, P=0.006) among patients in SIS group 0, group 1 and group 2. The 5-year OS rates of patients in the low NLR and high NLR groups were 82.67% and 56.16% respectively, with a statistically significant difference ( χ2=24.96, P<0.001) ; the 5-year OS rates of patients in the low LMR and high LMR groups were 66.85% and 88.17% respectively, with a statistically significant difference ( χ2=22.45, P<0.001) ; the 5-year OS rates of patients in the low SII and high SII groups were 86.14% and 69.02% respectively, with a statistically significant difference ( χ2=14.76, P<0.001). Univariate analysis showed that age ( HR=2.58, 95% CI: 1.54-4.32, P<0.001), T stage ( HR=2.41, 95% CI: 1.24-4.68, P=0.009), N stage ( HR=3.03, 95% CI: 1.85-4.94, P<0.001), TNM stage ( HR=3.61, 95% CI: 2.15-6.04, P<0.001), nerve invasion ( HR=1.97, 95% CI: 1.27-3.08, P=0.002), vascular invasion ( HR=2.31, 95% CI: 1.49-3.59, P<0.001), preoperative SIS 1 score ( HR=5.09, 95% CI: 1.57-16.56, P=0.007), SIS 2 score ( HR=11.05, 95% CI: 3.42-35.65, P<0.001), NLR ( HR=2.97, 95% CI: 1.90-4.64, P<0.001), LMR ( HR=0.31, 95% CI: 0.19-0.52, P<0.001), and SII ( HR=2.50, 95% CI: 1.54-4.06, P<0.001) were all independent influence factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection; multivariate analysis showed that age >60 years ( HR=2.27, 95% CI: 1.31-3.91, P=0.003), TNM stage Ⅲ-Ⅳ ( HR=7.08, 95% CI: 1.89-26.59, P=0.004), and preoperative SIS 2 score ( HR=4.02, 95% CI: 1.09-14.83, P=0.037) were all independent risk factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection. The nomogram model built based on the screened variables has high prediction accuracy: the C-index of the nomogram was 0.75. Conclusion:Age>60 years old, TNM stage Ⅲ-Ⅳ, SIS 2 score are all independent risk factors for postoperative prognosis of colorectal cancer. The nomograph model constructed by this method has high prediction accuracy.

Objective: To explore dynamics of parenting styles of adolescents from 1999 to 2019 from the perspective of intergenerational conflict, to provide support for family education and adolescent healthy development. Methods: Using a multistage stratified cluster random sampling method, the unified questionnaire was administered to 2 590 students in the same sampling junior and senior high schools in 1999, 2009, and 2019 using the Egna Minnen av Barndoms Uppfostran own memories of parental rearing practices in childhood(EMBU). Results: Overall there were differences in the nine factors of parenting styles across generations ( F = 12.07-72.52, P <0.01), with decreasing ratings of warmth and understanding of father and mother (F1, M1), over interference of father (F3) over generations(F1:46.72±9.41, 45.87±11.33, 43.61±11.27; M1:51.56±9.38, 51.03±11.59, 46.23± 12.27 ; F3:19.03±4.00, 18.29±4.32, 17.95±4.51), and all other parenting styles rated higher in 2019 than in 2009 and 1999(except for the over protection and over interference of mother, and punishment, firm control of mother). Parenting styles across generations (except for the rejection and denial of father among girls) showed gender difference.The overall gender trend coincided with the total population trend. Parenting styles across generations varied significantly among middle and high school students( F =3.92-47.27, P <0.05 ), changes in F1 and F3 factors coincided with the overall decreasing trend. Factor analysis showed that parenting styles could be classified into two dimensions, with varied factor loading across generation. Conclusion Intergenerational decreases in parental emotional warmth and paternal interfering are observed in a sex and grade specific manner. Based on the diversity of needs and population differentiation, optimal intervention for comprehensive health development of adolescents are in great need to keep pace with the times and promoting the high quality development of adolescents.

Objective:To investigate the safety and efficacy of chemoradiotherapy compared with chemotherapy after R0 excision in pN + esophageal squamous cell carcinoma (ESCC) patients. Methods:A retrospective analysis was performed on the pathological data of 99 pN + ESCC patients who underwent radical esophagectomy with R0 resection in Renmin Hospital of Wuhan University from January 2017 to December 2020. According to postoperative adjuvant treatment methods, the patients were divided into chemo-radiotherapy group ( n=41) and chemotherapy group ( n=58). The main outcome measures were disease-free survival (DFS), overall survival (OS) and the incidences of treatment-related adverse events. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors. Results:The median DFS and OS of 99 patients were 20.0 months and 28.0 months respectively. The 1- and 3-year DFS rates were 60.8% and 34.5% respectively. The 1- and 3-year OS rates were 83.5% and 40.2% respectively. The median DFS was 39.0 months in the chemoradiotherapy group and 10.0 months in the chemotherapy group, and the 1- and 3-year DFS rates were 79.4% vs. 48.3% and 57.3% vs. 24.5% respectively, with a statistically significant difference ( χ2=12.27, P<0.001). The median OS in the chemoradiotherapy group was not reached, and 21.0 months in the chemotherapy group, and the 1- and 3-year OS rates of the chemoradiotherapy group and chemotherapy group were 92.1% vs. 75.9% and 60.8% vs. 27.3%, with a statistically significant difference ( χ2=11.12, P=0.001). Univariate analysis showed that pN stage ( HR=0.58, 95% CI: 0.34-0.97, P=0.038), nerve invasion ( HR=1.88, 95% CI: 1.11-3.20, P=0.020) and adjuvant therapy ( HR=0.37, 95% CI: 0.21-0.67, P<0.001) were independent influencing factors of DFS in pN + ESCC patients. Adjuvant therapy ( HR=0.33, 95% CI: 0.17-0.66, P=0.001) was an independent factor influencing OS in pN + ESCC patients. Multivariate analysis showed that pN stage ( HR=0.54, 95% CI: 0.30-0.97, P=0.038) and adjuvant therapy ( HR=0.38, 95% CI: 0.21-0.69, P=0.001) were independent prognostic factors of DFS. Adjuvant therapy ( HR=0.34, 95% CI: 0.17-0.69, P=0.003) was an independent prognostic factor for OS. During adjuvant therapy, there were statistically significant differences in the incidences of leukopenia [65.85% (27/41) vs. 31.03% (18/58), χ2=11.75, P=0.001], thrombocytopenia [29.27% (12/41) vs. 10.34% (6/58), χ2=5.78, P=0.016], radioactive esophagitis [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001], and radioactive pneumonia [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001] between the two groups. Conclusion:Compared with chemotherapy, chemoradiotherapy can significantly improve DFS and OS of pN + ESCC patients with R0 resection after radical surgery, and the adverse reactions can be tolerated. pN stage and adjuvant therapy are independent prognostic factors for DFS, and adjuvant therapy is an independent prognostic factor for OS.

General education curriculum in Wuhan University has entered "3.0 era", in which general education curriculum of oncology has opened several cycles and been loved by the majority of students, meanwhile some problems have come up. In this article, the background of setting up general education curriculum of oncology in Wuhan University is reviewed. By sorting out teaching concepts and curriculum objectives, teaching content and organizational processes, teaching methods and evaluation methods and preliminary teaching effects, we emphatically discuss the role of clarifying teaching goals, optimizing curriculum designs, compiling basic teaching materials, improving teaching methods and reforming the evaluation system in promoting the setting and development of general education curriculum of oncology in comprehensive universities.

Objective:To observe effect of Jingulian capsule on the proliferation of human breast cancer MDA-MB-231 cells and investigate its action mechanism against triple negative breast cancer （TNBC）. Method:The ingredients of Jingulian capsule were identified by ultra-performance liquid chromatography-tandem mass spectrometry（UPLC-MS/MS）. The inhibitory effect of Jingulian capsule at different doses （0.125，0.25，0.5，1，and 2 g·L^-1） against the proliferation of MDA-MB-231 cells were detected by methyl thiazolyl tetrazolium （MTT） assay. After treatment for 24 h， the morphological changes in nuclear apoptosis of MDA-MB-231 cells were detected by Hoechst 33258 staining. The effect of different concentrations of Jingulian capsule on the apoptosis and cycle of MDA-MB-231 cells after different treatment time were determined by flow cytometry. The protein expression levels of Poly-ADP-ribose polymeras （PARP）， proto-oncogene c-Myc， cyclin B₁， and phosphorylated extracellular signal-regulated kinase （p-ERK） in each group were assayed by Western blot. Result:A total of 113 compounds in Jingulian capsule were identified by UPLC-MS/MS. As revealed by MTT assay，compared with blank group，Jingulian capsule （0.125，0.25，0.5，1，2 g·L^-1） significantly inhibited viability of MDA-MB-231 cells （P<0.01）， with the half maximal inhibitory concentration （ IC₅₀） of（0.13±0.02）g·L^-1. According to flow cytometry，compared with the blank group，Jingulian capsule at 1 g·L^-1 significantly induced the apoptosis of MDA-MB-231 cells （P<0.05）and Jingulian capsule at 0.5， 1 g·L^-1 obviously increased the number of MDA-MB-231 cells in S phase （P<0.05，P<0.01）. The results of Western blotting demonstrated that the protein expression levels of PARP，c-Myc，and cyclin B₁ in 0.5， 1 g·L^-1 Jingulian capsule groups were remarkably down-regulated as compared with those in the blank group（P<0.01）， and the protein expression level of p-ERK in 1 g·L^-1 Jingulian capsule group was also down-regulated （P<0.01）. Conclusion:Jingulian capsule is able to inhibit the proliferation of MDA-MB-231 cells，induce S phase cell cycle arrest， and promote their apoptosis， which may be related to the inactivation of the MAPK signaling pathway.

Objective:To evaluate the expression and clinical significance of γ-glutamylcyclotransferase (GGCT) in patients with bladder urothelial cell carcinoma.Methods:Immunohistochemical staining for GGCT were performed on tissue sections of 86 patients with bladder urothelial cell carcinoma and 10 normal controls, and the correlations between GGCT and clinicopathological characteristics and the prognosis were analyzed.Results:The positive rate of the expression of GGCT in 86 cases of bladder urothelial cell carcinoma was 61.6% (53/86). GGCT protein was located mainly in cancer cell cytoplasm, and it can be seen in the nucleus of the tumor cells in some cases. The level of GGCT expression was positively related to pathological classification ( P<0.001), stage ( P=0.020), and tumor size ( P=0.025). Immunohistochemical semiquantitative analysis showed that the expression of GGCT in patients with T1 stage of non-muscle invasion bladder urothelial cell carcinoma was significantly higher than that with Ta stage ( P=0.034). Kaplan-Meier analysis showed that the expression of GGCT was correlated with the recurrence-free survival in patients with non-muscle invasive bladder cancer, the recurrence-free survival rate was lower in the GGCT positive group ( P=0.029). Multivariate COX regression analysis showed that the pathological stage ( OR=5.029, P=0.009) and the number of tumors ( OR=3.320, P=0.024)were the independent risk factors for recurrence-free survival in patients with early urothelial cell carcinoma of the bladder. Conclusions:The expression of GGCT is significantly increased in bladder urothelial cell carcinoma and is related to the malignant biological behavior and progression of tumor. Patients with GGCT positive early bladder tumor are inclined to recur.