To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To explore the clinical effect of stereotactic body radiotherapy(SBRT)combined with dendritic cell-cytokine-induced killer cell(DC-CIK)immunotherapy in the treatment of centrally-located locally advanced non-small cell lung cancer(LA-NSCLC).Methods A total of 113 patients with centrally-located LA-NSCLC admitted from January 2022 to March 2024 were divided into the observation group(n=56)and the control group(n=57)by using the random number table method.The observation group was treated with SBRT combined with DC-CIK immunotherapy,while the control group was treated with SBRT.The clinical efficacy of the two groups after treatment,as well as the levels of tumor markers,immune function indicators and inflammatory indicators before and after treatment,was compared.The adverse reactions during the treatment period and the short-term survival during the 12-month follow-up of the two groups were recorded.Results Compared with the control group,both objective response rate and disease control rate of the observation group were higher(P<0.05).After treatment,the levels of serum carcinoembryonic antigen,cytokeratin 19 fragment and cancer antigen 125 in both groups were lower than those before treatment,and lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in the control group were lower than those before treatment,while the level of CD8+was higher than that before treatment(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+in the observation group were higher than those before treatment and also higher than those in the control group,while the level of CD8+was lower than that before treatment and also lower than that in the control group(P<0.05,P<0.01).After treatment,the interferon-γ level in the observation group was higher than that before treatment and also higher than that in the control group,while the levels of tumor necrosis factor-α and interleukin-6 were lower than those before treatment and also lower than those in the control group(P<0.05,P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups during the treatment period(P>0.05).The overall survival rate of the observation group at 12-month follow-up was higher,and the median survival time was longer,as compared with the control group(P<0.05).Conclusion SBRT combined with DC-CIK immunotherapy has a definite effect in the treatment of patients with centrally-located LA-NSCLC.It can significantly improve the immune function of patients,reduce the levels of tumor markers,alleviate inflammatory responses,increase short-term survival rates,prolong survival time,and does not significantly increase adverse reactions,offering good safety and reliability.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To explore the clinical effect of stereotactic body radiotherapy(SBRT)combined with dendritic cell-cytokine-induced killer cell(DC-CIK)immunotherapy in the treatment of centrally-located locally advanced non-small cell lung cancer(LA-NSCLC).Methods A total of 113 patients with centrally-located LA-NSCLC admitted from January 2022 to March 2024 were divided into the observation group(n=56)and the control group(n=57)by using the random number table method.The observation group was treated with SBRT combined with DC-CIK immunotherapy,while the control group was treated with SBRT.The clinical efficacy of the two groups after treatment,as well as the levels of tumor markers,immune function indicators and inflammatory indicators before and after treatment,was compared.The adverse reactions during the treatment period and the short-term survival during the 12-month follow-up of the two groups were recorded.Results Compared with the control group,both objective response rate and disease control rate of the observation group were higher(P<0.05).After treatment,the levels of serum carcinoembryonic antigen,cytokeratin 19 fragment and cancer antigen 125 in both groups were lower than those before treatment,and lower in the observation group than in the control group(P<0.05,P<0.01).After treatment,the levels of CD3+,CD4+,and CD4+/CD8+in the control group were lower than those before treatment,while the level of CD8+was higher than that before treatment(P<0.05).After treatment,the levels of CD3+,CD4+and CD4+/CD8+in the observation group were higher than those before treatment and also higher than those in the control group,while the level of CD8+was lower than that before treatment and also lower than that in the control group(P<0.05,P<0.01).After treatment,the interferon-γ level in the observation group was higher than that before treatment and also higher than that in the control group,while the levels of tumor necrosis factor-α and interleukin-6 were lower than those before treatment and also lower than those in the control group(P<0.05,P<0.01).There was no significant difference in the incidence of adverse reactions between the two groups during the treatment period(P>0.05).The overall survival rate of the observation group at 12-month follow-up was higher,and the median survival time was longer,as compared with the control group(P<0.05).Conclusion SBRT combined with DC-CIK immunotherapy has a definite effect in the treatment of patients with centrally-located LA-NSCLC.It can significantly improve the immune function of patients,reduce the levels of tumor markers,alleviate inflammatory responses,increase short-term survival rates,prolong survival time,and does not significantly increase adverse reactions,offering good safety and reliability.

To explore the interaction between ASFV capsid protein M1249L and host from the host cellular perspective,M1249L was selected for constructing the bait plasmid(pGBKT7-M1249L)to screen the bone marrow-derived macrophages(BMDMs)cDNA library.After again co-transform and sequence alignment,20 candidate interacting host proteins were screened,such as IL-1β,CTSB and DNAJA3.And then,co-immunoprecipitation assay was performed to verify the interaction be-tween M1249L and host proteins.GO ontology(GO)and KEGG pathway enrichment analyses re-vealed that biological regulation,cellular communication and response to stimulus and others were enriched in biological processes.And these host proteins could share some pathways,including toll-like receptor signaling pathway and Nod-like receptor signaling pathway.Therefore,the results provides the theoretical basis for further research on the mechanism of ASFV M1249L in viral in-fection and immune regulation.

Objective To investigate the mental health status and its influencing factors among elderly hypertensive patients from Rural Areas of Chuxiong and Honghe Prefecture in Yunnan.Methods Multi-stage random sampling method was adopted to select elderly hypertensive patients from rural Yi ethnic areas in Yunnan.Questionnaires were used to collect their basic information and mental health status.Multivariate logistic regression was performed to explore the influencing factors of mental health among the elderly hypertensives.Results 21.82%(209/958)of elderly people with hypertension have poor mental health status in Chuxiong and Honghe Prefecture,Yunnan.Age of 80-89 years(OR = 2.395,P<0.05)and over 90 years(OR = 3.293,P<0.05),as well as physical disability(OR = 2.037,P<0.05),were risk factors for poor mental health.Compared with those who rated their economic situation as very difficult,rating as somewhat difficult(OR = 0.490,P<0.05),moderate(OR = 0.632,P<0.05)and relatively affluent(OR = 0.344,P<0.05),having a spouse(OR = 0.655,P<0.05),received full concern from the offspring(OR = 0.411,P<0.05)and maintain good relationships with offspring(OR = 0.339,P<0.05)were protective factors.Conclusions The mental health status of elderly people with hypertension is relatively poor in rural areas of Chuxiong and Honghe Prefecture in Yunnan Province.Special attention should be paid to the mental health of older and physically disabled elderly hypertensives.Economic and mental support from children was crucially important in improving the mental health of elderly hypertensive patients in rural areas of Chuxiong and Honghe Prefecture in Yunnan Province.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To compare the clinical efficacy of laparoscopic right colon cancer radical resection(CME+D3,60 cases) based on membrane anatomy and traditional laparoscopic right colon cancer radical resection(CME/D3, 120 cases).Methods:A retrospective cohort study was used to collect the consecutively admitted cases undergoing laparoscopic radical right colon cancer resection at the Department of Colorectal Surgery, Shanxi Hospital from Jan 2018 to Jun 2020.The postoperative data , postoperative complications, follow-up outcomes were compared between the two groups.Results:Compared with the CME/D3 group, that the based on membrane anatomy(CME+D3) group had a decreased intraoperative blood loss [(79.3±16.7) ml vs. (103.6±20.8) ml, t=-3.894, P<0.001],and more lymph node harvest [(27.0±5.1) vs. (25.1±6.2), t=2.138, P=0.034]; The sectional grading of surgical specimens was also better than that in the traditional operation group(χ 2=4.146, P=0.042); while the operation time was slightly longer than that of the traditional operation group [(161.1±18.4) minutes vs.(142.6±19.5) minutes, t=-6.166, P<0.001]. There was no significant difference in the length of specimen resection, postoperative exhaust time, hospital stay, incidence of postoperative complications, proportion of unplanned reoperation within 30 days, re-admission within 30 days, and mortality within 30 days ( all P>0.05). The median follow-up time was 36.7 (5.3-48.7) months, and there was no significant difference in overall survival rates between the two groups ( P>0.05); The difference in disease-free survival rates between the two groups is significant(χ 2=4.246, P=0.039). Conclusions:Compared with the traditional laparoscopic right colon cancer radical surgery (CME/D3),laparoscopic radical resection of right colon cancer (CME+D3) based on membrane anatomy reduces intraoperative bleeding, improves the number of lymph node dissection and specimen quality, and has higher 1-year and 3-year disease-free survival rate .