Esophageal squamous cell carcinoma is the main histological type of esophageal cancer in China, which seriously threatens the health of people. The application of immunotherapy, mainly immune checkpoint inhibitors, has greatly improved the prognosis of patients with esophageal squamous cell carcinoma, but the efficacy of treatment is still limited. Tertiary lymphoid structure (TLS) is an ectopic organized lymphoid structure that accumulates in non-lymphoid organs. Previous studies have found that TLS in esophageal squamous cell carcinoma is associated with better patient outcomes and enhanced immunotherapy efficacy. Based on current researches about TLS in esophageal squamous cell carcinoma, this paper reviews the relationship between TLS and the prognosis and immunotherapy of patients. We hope to provide reference for the precise immunotherapy of esophageal squamous cell carcinoma.

Objective:To investigate the effect of elimination,combination,rearrangement and simplification(ECRS)management combined with risk assessment on reducing the incidence of multidrug-resistant bacteria infections of patients who received mechanical ventilation in intensive care unit(ICU).Methods:The management mode of prevention and control for multidrug-resistant bacteria infections of patients in ICU was optimized on the basis of ECRS management combined with risk assessment.A total of 600 patients who received mechanical ventilation in ICU of Jiuquan Hospital of Shanghai General Hospital(Jiuquan People's Hospital)from January 2022 to December 2023 were selected.According to different management methods,these patients were divided into a control group and an observation group,with 300 cases in each group.The control group was managed by using the risk assessment management method,while the observation group was managed by using the ECRS management on the basis of risk assessment management method.The indicators of respiratory function,patients'satisfaction score,stay time in ICU,time of mechanical ventilation and incidence of multidrug-resistant bacteria were compared between the two groups.Results:The mean value of the ratio of forced expiratory volume in one second(FEV1)to forced vital capacity(FVC)(FEV1/FVC),and the FEV1 level in observation group by using ECRS management combined with risk assessment method were respectively(78.69±4.65)%and(1.58±0.24)L,both of which were higher than those of control group,and the differences of them between two groups were statistically significant(t=16.483,11.742,P<0.05).The average scores of work efficiency,emergency response capability,professional ethics,isolation and resettlement,and overall patients'satisfaction in the observation group were respectively(23.12±1.20),(23.34±1.08),(23.65±1.10),(23.80±1.05)and(92.24±4.37),all of which were higher than those in the control group,and the differences of them between two groups were statistically significant(t=22.176,27.903,22.373,31.364,13.963,P<0.05).The average ICU stay time and the average time of mechanical ventilation were respectively(14.15±1.60)and(9.15±2.13)days in the observation group,both of which were lower than those in the control group,and the differences of them between two groups were statistically significant(t=16.872,15.410,P<0.05).The incidence of multidrug-resistant bacteria was 0.33%in 300 patients of the observation group,which was lower than that of the control group,with a statistically significant difference(x2=4.561,P<0.05).Conclusion:The application of ECRS management combined with risk assessment in the management of ICU for patients who receive mechanical ventilation can protect respiratory function of patients,and decrease the risk of occurring the infection of multidrug-resistant bacteria,and reduce ICU stay time and the time of mechanical ventilation of patients,and improve patients'satisfaction.

Objective:To investigate the effect of elimination,combination,rearrangement and simplification(ECRS)management combined with risk assessment on reducing the incidence of multidrug-resistant bacteria infections of patients who received mechanical ventilation in intensive care unit(ICU).Methods:The management mode of prevention and control for multidrug-resistant bacteria infections of patients in ICU was optimized on the basis of ECRS management combined with risk assessment.A total of 600 patients who received mechanical ventilation in ICU of Jiuquan Hospital of Shanghai General Hospital(Jiuquan People's Hospital)from January 2022 to December 2023 were selected.According to different management methods,these patients were divided into a control group and an observation group,with 300 cases in each group.The control group was managed by using the risk assessment management method,while the observation group was managed by using the ECRS management on the basis of risk assessment management method.The indicators of respiratory function,patients'satisfaction score,stay time in ICU,time of mechanical ventilation and incidence of multidrug-resistant bacteria were compared between the two groups.Results:The mean value of the ratio of forced expiratory volume in one second(FEV1)to forced vital capacity(FVC)(FEV1/FVC),and the FEV1 level in observation group by using ECRS management combined with risk assessment method were respectively(78.69±4.65)%and(1.58±0.24)L,both of which were higher than those of control group,and the differences of them between two groups were statistically significant(t=16.483,11.742,P<0.05).The average scores of work efficiency,emergency response capability,professional ethics,isolation and resettlement,and overall patients'satisfaction in the observation group were respectively(23.12±1.20),(23.34±1.08),(23.65±1.10),(23.80±1.05)and(92.24±4.37),all of which were higher than those in the control group,and the differences of them between two groups were statistically significant(t=22.176,27.903,22.373,31.364,13.963,P<0.05).The average ICU stay time and the average time of mechanical ventilation were respectively(14.15±1.60)and(9.15±2.13)days in the observation group,both of which were lower than those in the control group,and the differences of them between two groups were statistically significant(t=16.872,15.410,P<0.05).The incidence of multidrug-resistant bacteria was 0.33%in 300 patients of the observation group,which was lower than that of the control group,with a statistically significant difference(x2=4.561,P<0.05).Conclusion:The application of ECRS management combined with risk assessment in the management of ICU for patients who receive mechanical ventilation can protect respiratory function of patients,and decrease the risk of occurring the infection of multidrug-resistant bacteria,and reduce ICU stay time and the time of mechanical ventilation of patients,and improve patients'satisfaction.

Objective·To explore the regulatory mechanism of folate cycle metabolism in the immunosuppressive effect of myeloid derived suppressor cells(MDSCs).Methods·Bone marrow cells were isolated from C57BL/6 mice and cultured in RPMI 1640 medium supplemented with GM-CSF,G-CSF,and IL-6 to induce MDSCs in vitro.PD-L1 expression level and ROS production level of induced MDSCs were detected by flow cytometry.CD8+T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads,labeled with Celltrace violet,and then co-cultured with MDSCs.After 72 h,proliferation was assessed by flow cytometry.Folate cycle-related metabolic enzymes in MDSCs were detected by real-time quantitative PCR.MDSCs were treated with folate cycle metabolic enzyme MTHFD2 inhibitor DS18561882(DS18)and folic acid antagonist Pemetrexed.ROS and mitoROS production in MDSCs were assessed by flow cytometry.CD8+T cells were enriched from the spleen by MACS with anti-CD8a-conjugated microbeads,labeled with Celltrace violet,and then co-cultured with Pemetrexed or DS18-treated MDSCs.After 72 h,proliferation was assessed by flow cytometry.Transcript levels of folate cycle-related metabolic enzymes in pemetrexed or DS18-treated MDSCs were detected by RNAseq.A subcutaneous tumor mouse model of colon cancer was established.From the tenth day post-implantation,tumor-bearing mice were intraperitoneally injected with Pemetrexed(200 mg/kg)and tumor size was recorded for tumor growth curve.On the fourteenth day,mice were sacrificed,and tumors were harvested.MC38 tumor-bearing mice were treated with isotype antibody,anti-CD8 monoclonal antibody(1 mg/kg,deplete CD8+T cells),Pemetrexed(200 mg/kg),and combination of Pemetrexed with anti-CD8 antibody.MC38 tumor-bearing mice were treated with isotype antibody,anti-Gr1 monoclonal antibody(1.25 mg/kg,clearing MDSCs),combination of Pemetrexed with anti-Gr1 antibody.On the tenth day after implantation,tumor-bearing mice were treated with Pemetrexed(50 mg/kg),anti-PD-1 monoclonal antibody(250 μg/kg),Pemetrexed,and combination of Pemetrexed with anti-PD-1 antibody.Results·Flow cytometry data showed that PD-L1 level and ROS production were increased in induced MDSCs,and CD8+T cell proliferation was also suppressed significantly.qPCR data revealed the expression of folate cycle-related metabolic enzymes MTHFD2 and others was increased in MDSCs.The accumulation of MDSCs was affected by DS18 or Pemetrexed,ROS production in MDSCs was reduced,and the immunosuppression of CD8+T cells was relieved.RNA-seq results showed that genes related to MDSCs differentiation,such as S100 calc-binding protein A8,and genes related to MDSCs inhibition,such as cytochrome b-245β chain,which is related to ROS production,were also down-regulated after treatment with two folic acid cycling inhibitors.Tumor growth was suppressed by Pemetrexed.Tumor progression was promoted by combination of Pemetrexed with anti-CD8 antibody,compared with Pemetrexed monotherapy.However,tumor growth delay was inhibited by combination of Pemetrexed and anti-CD8,compared with anti-CD8 monotherapy.Tumor growth delay was caused by MDSCs depletion.But tumor growth was promoted by combination of pemetrexed and anti-Gr1,compared with pemetrexed monotherapy.Tumor growth was restricted by combination of pemetrexed and anti-PD-1 antibody,compared with anti-PD-1 monotherapy.Conclusion·Pemetrexed relies on CD8+T cells for anti-tumor effects and further retards tumor growth by reprogramming MDSCs to an anti-tumor phenotype.Modulating MDSCs by targeting folate cycle could impair their immunosuppressive ability and enhance the efficacy of immune checkpoint blockade in cancer treatment.