Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Extracorporeal membrane oxygenation (ECMO) serves as an advanced life support technology and plays a critical role in treating critically ill patients with severe cardiopulmonary failure. However, the unique physiological and pathological changes during pregnancy present numerous challenges and special considerations for the application of ECMO in obstetrics. Given the current lack of unified guidelines specifically for obstetric ECMO, clinical practice often relies on adapting general ECMO guidelines in combination with obstetric-specific factors. This article systematically reviews the core principles of existing general ECMO guidelines, provides an in-depth analysis of the impact of gestational physiological and pathological characteristics on ECMO application, and discusses the particularities and necessary adaptations of obstetric ECMO in terms of indications, anticoagulation strategies, parameter adjustment, multidisciplinary collaboration, and emergency management. Furthermore, it proposes strategies suitable for domestic clinical practice. The article also addresses existing difficulties and limitations not covered by current guidelines and calls for the urgent development of specialized obstetric ECMO guidelines to provide clinicians with more standardized and safer decision-making support, ultimately improving outcomes for critically ill pregnant patients and newborns.

Cancer is one of the major diseases of high morbidity and mortality worldwide,and its therapeutic approaches are facing great challenges.Immunotherapy,especially the activation of innate immunity represented by the cGAS-STING signaling pathway,is the current research hotspot in tumor immunotherapy.Activation of innate immune response by gas therapy is the latest development in tumor therapeutic approaches,especially the use of gas signaling molecules(NOx CO,H2S and SO2)to activate the cGAS-STING signaling pathway to induce intrinsic immunity of the organism,which leads to anti-tumor immunotherapy.Although intrinsic immunity activated by gas signaling molecules plays an important role in tumor immunotherapy,few reviews have been reported on its association with the cGAS-STING signaling mechanism.In this paper,we will comprehensively describe how gas signaling molecules damage the mitochondrial matrix and DNA damage through oxidative/nitrosative stress,thereby activating the cGAS-STING signaling pathway and triggering the innate immune cascade,aiming to summarize the process of activation of anti-tumor immune effects by gas signaling molecules,and to provide more references for the gas therapies in the future anti-tumor immunity research.

Extracorporeal membrane oxygenation (ECMO) serves as an advanced life support technology and plays a critical role in treating critically ill patients with severe cardiopulmonary failure. However, the unique physiological and pathological changes during pregnancy present numerous challenges and special considerations for the application of ECMO in obstetrics. Given the current lack of unified guidelines specifically for obstetric ECMO, clinical practice often relies on adapting general ECMO guidelines in combination with obstetric-specific factors. This article systematically reviews the core principles of existing general ECMO guidelines, provides an in-depth analysis of the impact of gestational physiological and pathological characteristics on ECMO application, and discusses the particularities and necessary adaptations of obstetric ECMO in terms of indications, anticoagulation strategies, parameter adjustment, multidisciplinary collaboration, and emergency management. Furthermore, it proposes strategies suitable for domestic clinical practice. The article also addresses existing difficulties and limitations not covered by current guidelines and calls for the urgent development of specialized obstetric ECMO guidelines to provide clinicians with more standardized and safer decision-making support, ultimately improving outcomes for critically ill pregnant patients and newborns.

Objective:To investigate the impact of different treatment sequences of immunotherapy combined with chemoradiotherapy (CRT) as the first-line therapy on the prognosis of patients with stage III non-small cell lung cancer (NSCLC).Methods:Clinical data of 112 patients with stage III NSCLC treated at the Fourth Hospital of Hebei Medical University from January 2019 to December 2021 were retrospectively collected, with follow-up continued until December 31, 2023. According to the sequence of CRT and immune checkpoint inhibitors (ICIs) therapy, patients were divided into 3 groups: ICIs simultaneous with CRT (sICR, n=20), chemotherapy combined with ICIs followed by CRT (CI-CR, n=53), and CRT followed by consolidative ICIs (CR-I, n=39). Analyses were performed before and after propensity score matching (PSM). Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, and prognostic factors were identified through multivariate Cox regression analysis. Results:The median overall survival (OS) and progression-free survival (PFS) for the entire cohort were 30.1 months (95% CI: 21.4-38.9) and 12.8 months (95% CI: 9.14-16.1), respectively. Before PSM: No significant differences were observed in OS and PFS among the 3 groups ( χ2=0.18, 1.05; P=0.669, 0.305). However, OS in the sICR and CR-I groups was significantly better than that in the CI-CR group ( χ2=4.43, 6.11; P=0.035, 0.013). After PSM: Each group included 17 patients. There were no significant differences in OS or PFS among the 3 groups ( χ2=2.50, 2.74; P=0.287, 0.254), and pairwise comparisons also showed no significant differences. Multivariate Cox regression analysis revealed that clinical stage ( HR=3.392, 95% CI: 1.215-9.470, P=0.020), number of immunotherapy cycles ( HR=0.312, 95% CI: 0.100-0.972, P=0.044), and treatment response ( HR=6.566, 95% CI: 1.705-25.284, P=0.006) were independent prognostic factors for OS. After PSM, the numbers of patients with grade ≥2 treatment-related adverse events were 13 in the sICR group, 10 in the CI-CR group, and 9 in the CR-I group, with no significant differences among them ( χ2=2.181, P=0.336). Conclusions:First-line immunotherapy combined with chemoradiotherapy showed favorable clinical efficacy in locally advanced NSCLC compared to other studies, but the treatment sequence did not significantly affect prognosis. It is recommended that immunotherapy be administered for at least four cycles.

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Objective:To explore the impacts of two radiotherapy modalities, elective nodal irradiation (ENI) and involved-field irradiation (IFI), on the prognosis of patients with clinical T 1~4N 0M 0 esophageal squamous cell carcinoma (ESCC) treated with definitive (chemotherapy) radiotherapy. Methods:A retrospective analysis was conducted on the prognosis of 324 patients with clinical T 1-4N 0M 0 ESCC, focusing on the impacts of ENI and IFI on the prognosis of these patients. Propensity score matching (PSM) analysis was performed based on the different composition ratios of the two groups, and stratified analysis was conducted for patients of different stages. Results:All the patients presented a median overall survival (OS) of 33.1 months (95% CI: 28.1-38.1) and a median progression-free survival (PFS) of 22.3 months (95% CI: 18.2-26.4). There were 97 patients in the ENI group and 227 patients in the IFI group. The ENI group exhibited higher OS and PFS than the IFI group ( χ2 = 4.31, 4.10, P < 0.05). After 1∶1 PSM analysis, each of the groups contained 75 cases. Multivariate analysis revealed that independent factors affecting patient OS included patient age, gross tumor volume (GTV), and irradiation modality ( χ2 = 7.93, 5.88, 4.59, P < 0.05) and PFS ( χ2 = 7.10, 5.26, 3.39, P < 0.05). Further stratified analysis indicated that ENI yielded significantly better efficacy than IFI for patients with cT 1 and T 2stage ESCC ( χ2 = 9.41, 7.88, P < 0.05). However, this advantage was not found in T 3 and T 4 patients ( P > 0.05). There was no statistically significant difference in the incidence of radiation esophagitis and radiation pneumonia between both groups ( P > 0.05). Conclusions:Patients with clinical T 1-4N 0M 0 ESCC who undergone definitive (chemotherapy) radiotherapy may benefit from ENI, particularly those in the cT 1 and cT 2 stages, for whom ENI is recommended for definitive radiotherapy.

Objective:To explore the impacts of two radiotherapy modalities, elective nodal irradiation (ENI) and involved-field irradiation (IFI), on the prognosis of patients with clinical T 1~4N 0M 0 esophageal squamous cell carcinoma (ESCC) treated with definitive (chemotherapy) radiotherapy. Methods:A retrospective analysis was conducted on the prognosis of 324 patients with clinical T 1-4N 0M 0 ESCC, focusing on the impacts of ENI and IFI on the prognosis of these patients. Propensity score matching (PSM) analysis was performed based on the different composition ratios of the two groups, and stratified analysis was conducted for patients of different stages. Results:All the patients presented a median overall survival (OS) of 33.1 months (95% CI: 28.1-38.1) and a median progression-free survival (PFS) of 22.3 months (95% CI: 18.2-26.4). There were 97 patients in the ENI group and 227 patients in the IFI group. The ENI group exhibited higher OS and PFS than the IFI group ( χ2 = 4.31, 4.10, P < 0.05). After 1∶1 PSM analysis, each of the groups contained 75 cases. Multivariate analysis revealed that independent factors affecting patient OS included patient age, gross tumor volume (GTV), and irradiation modality ( χ2 = 7.93, 5.88, 4.59, P < 0.05) and PFS ( χ2 = 7.10, 5.26, 3.39, P < 0.05). Further stratified analysis indicated that ENI yielded significantly better efficacy than IFI for patients with cT 1 and T 2stage ESCC ( χ2 = 9.41, 7.88, P < 0.05). However, this advantage was not found in T 3 and T 4 patients ( P > 0.05). There was no statistically significant difference in the incidence of radiation esophagitis and radiation pneumonia between both groups ( P > 0.05). Conclusions:Patients with clinical T 1-4N 0M 0 ESCC who undergone definitive (chemotherapy) radiotherapy may benefit from ENI, particularly those in the cT 1 and cT 2 stages, for whom ENI is recommended for definitive radiotherapy.

Objective:To evaluate the efficacy and prognostic factors of radiotherapy combined with immunotherapy as the first-line treatment for patients with locally advanced or metastatic esophageal squamous cell carcinoma (LA/M ESCC).Methods:A single-center, retrospective analysis was conducted for the recent efficacy, survival, prognostic factors, post-treatment failure modes, and treatment-related adverse reactions of 57 LA/M ESCC patients eligible for enrollment.Results:The entire group of patients had 1-, 2-, and 3-year overall survival (OS) of 86.0%, 57.5%, and 53.9%, respectively and 1-, 2-, and 3-year progression-free survival (PFS) of 61.4%, 31.0%, and 31.0%, respectively. The median OS was not reached, and the median PFS was 15.0 (95% CI: 10.77-19.23) months. These patients had an overall response rate (ORR) of 80.7% (46/57) and a disease control rate (DCR) of 94.7% (54/57). As indicated by the result of the multivariate analysis, the independent prognostic factors affecting the OS of the patients included their age, clinical stage, number of immunotherapy cycles, and recent efficacy ( HR = 0.25, 2.58, 0.35, 4.05, P < 0.05), and the independent factors influencing the PFS of the patients included their clinical stage and recent efficacy ( HR = 2.27, 1.97, P < 0.05). There were no statistically significant differences in the effects of irradiation ranges and the combination modes of immunologic drugs and chemoradiotherapy on both OS and PFS of the patients ( P > 0.05). A total of 32 patients suffered post-treatment failure. After the second treatment, they had 1- and 2-year OS of 55.7% and 25.3%, respectively, with median OS of 14.0 (95% CI: 5.17-22.83) months. A total of 26 cases experienced treatment-associated adverse reactions of grades 2 or higher during and after treatment. Conclusions:The combination of radiotherapy and immunotherapy is effective and safe as the first-line treatment for LA/M ESCC patients. The post-treatment failure modes still include local recurrence and distant metastasis. Therefore, such combination merits further investigation.