Objective:To investigate effect of cedrol on radiosensitivity of prostate cancer(PCa)cells and its mechanism.Methods:mRNA and protein expressions of cGAS and STING in PCa tissues and cells were detected by qRT-PCR and Western blot,respectively.Human PCa cells PC-3 were divided into control group,radiation group,cedrol group,combination group and inhibitor group.Radiosensitivity of cells in each group was detected by plate cloning test;apoptosis,migration and invasion were detected by flow cytometry,scratch test and Transwell chamber,respectively;γ-H2AX immunofluorescence staining was used to analyze effect of cedrol on DNA damage repair;after PC-3 cells and CD8+T cells were co-cultured,cells were divided into T cell group,co-culture group,cedrol group and inhibitor group,MTT and flow cytometry were used to detect proliferation and apoptosis of CD8+T cells,IFN-γ,IL-2 and TNF-α levels in supernatant of CD8+T cells were detected by ELISA;Western blot was used to detect prolife-rating cell nuclear antigen(PCNA),Bcl-2 associated protein(Bax),programmed death recepter ligand 1(PD-L1)and cGAS-STING signal pathway protein.Results:cGAS and STING protein and mRNA expressions in PCa tissues and cells were decreased(P<0.05),which were lowest in PC-3 cells.Compared with control group,colony formation rate,cell survival rate,scratch healing rate and cell inva-sion rate of PC-3 cells in radiation group and cedrol group were decreased obviously,apoptosis rate and number of γ-H2AX focus were increased obviously(P<0.05);compared with radiation group and cedrol group,combined group inhibited proliferation,migration and invasion of PC-3 cells,and induced DNA damage and apoptosis(P<0.05);inhibitor group attenuated inhibitory effect of com-bined group on proliferation,migration and invasion of PC-3 cells,and promoted DNA damage and apoptosis(P<0.05);compared with T cell group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in co-culture group were decreased,apoptosis rate was in-creased(P<0.05);compared with co-culture group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in cedrol group were in-creased,apoptosis rate was decreased(P<0.05);compared with cedrol group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in inhibitor group were decreased,apoptosis rate was increased(P<0.05).Compared with control group,expressions of PCNA and PD-L1 proteins in PC-3 cells in cedrol group were reduced obviously,expressions of Bax,cGAS and STING proteins were increased obviously(P<0.05);inhibitors of cGAS-STING pathway could reverse effect of cedrol on above proteins(P<0.05).Conclusion:Cedrol may enhance radiosensitivity of PCa cells by activating cGAS-STING signal pathway and inhibiting immune escape.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objective:To investigate effect of cedrol on radiosensitivity of prostate cancer(PCa)cells and its mechanism.Methods:mRNA and protein expressions of cGAS and STING in PCa tissues and cells were detected by qRT-PCR and Western blot,respectively.Human PCa cells PC-3 were divided into control group,radiation group,cedrol group,combination group and inhibitor group.Radiosensitivity of cells in each group was detected by plate cloning test;apoptosis,migration and invasion were detected by flow cytometry,scratch test and Transwell chamber,respectively;γ-H2AX immunofluorescence staining was used to analyze effect of cedrol on DNA damage repair;after PC-3 cells and CD8+T cells were co-cultured,cells were divided into T cell group,co-culture group,cedrol group and inhibitor group,MTT and flow cytometry were used to detect proliferation and apoptosis of CD8+T cells,IFN-γ,IL-2 and TNF-α levels in supernatant of CD8+T cells were detected by ELISA;Western blot was used to detect prolife-rating cell nuclear antigen(PCNA),Bcl-2 associated protein(Bax),programmed death recepter ligand 1(PD-L1)and cGAS-STING signal pathway protein.Results:cGAS and STING protein and mRNA expressions in PCa tissues and cells were decreased(P<0.05),which were lowest in PC-3 cells.Compared with control group,colony formation rate,cell survival rate,scratch healing rate and cell inva-sion rate of PC-3 cells in radiation group and cedrol group were decreased obviously,apoptosis rate and number of γ-H2AX focus were increased obviously(P<0.05);compared with radiation group and cedrol group,combined group inhibited proliferation,migration and invasion of PC-3 cells,and induced DNA damage and apoptosis(P<0.05);inhibitor group attenuated inhibitory effect of com-bined group on proliferation,migration and invasion of PC-3 cells,and promoted DNA damage and apoptosis(P<0.05);compared with T cell group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in co-culture group were decreased,apoptosis rate was in-creased(P<0.05);compared with co-culture group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in cedrol group were in-creased,apoptosis rate was decreased(P<0.05);compared with cedrol group,A490,levels of IFN-γ,IL-2 and TNF-α in CD8+T cells in inhibitor group were decreased,apoptosis rate was increased(P<0.05).Compared with control group,expressions of PCNA and PD-L1 proteins in PC-3 cells in cedrol group were reduced obviously,expressions of Bax,cGAS and STING proteins were increased obviously(P<0.05);inhibitors of cGAS-STING pathway could reverse effect of cedrol on above proteins(P<0.05).Conclusion:Cedrol may enhance radiosensitivity of PCa cells by activating cGAS-STING signal pathway and inhibiting immune escape.

In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

Background/Aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear. Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activitygroups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using surveylogistic regression and restricted cubic splines. Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03). Conclusions Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

Humans ; Receptors, Chimeric Antigen/therapeutic use* ; DNA-Binding Proteins/genetics* ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Cell- and Tissue-Based Therapy ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.