The treatment of non-small cell lung cancer (NSCLC) faces significant challenges due to tumor heterogeneity and the complexity of the immune microenvironment. The cyclic GMP-AMP synthase (cGAS) -stimulator of interferon gene (STING) signaling pathway plays a dual role in NSCLC, serving both as a crucial hub for anti-tumor immunity and as a potential driver of metastasis. The clinical translation of STING agonists confronts a series of challenges, including delivery barriers, double-edged sword effects, and patient heterogeneity. Consequently, exploring the combined application of STING agonists with radiotherapy/chemotherapy, immune checkpoint inhibitors, and novel immunotherapies, alongside leveraging artificial intelligence-driven multi-omics models for individualized prediction and treatment, holds significant importance. A deeper understanding of the molecular regulatory network of the cGAS-STING signaling pathway and its dynamic functions within the tumor microenvironment is essential for overcoming the current clinical challenges of targeted therapies and advancing the precision development of NSCLC immunotherapy strategies.

Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

OBJECTIVETo investigate the efficacy and safety of the Chinese herbal therapeutic regimen of activating blood circulation (TRABC) in treatment of hypertensive intracerebral hemorrhage (HICH).

METHODSThis was a multi-center prospective randomized open-label blinded-endpoint (PROBE) trial with HICH admitted to 12 hospitals. Totally 240 participants were randomized to the treatment group treated with TRABC in addition to conventional Western treatment or the control group with conventional Western treatment equally for 3 months. Primary outcome was degree of disability as measured by modified Rankin Scale (mRS). Secondary outcomes were the absorption of hematoma and edema, National Institutes of Health Stroke Scale (NIHSS) scores and patient-reported outcome measures for stroke and Barthel activities of daily living index. Adverse events and mortality were also recorded.

RESULTSAfter 3 months of treatment, the rate of mRS 0-1 and mRS 0-2 in the treatment group was 72.5% and 80.4%, respectively, and in the control group 48.1% and 63.9%, respectively, with a significant difference between groups (P<0.01). Hematoma volume decreased significantly at day 7 of treatment in the treatment group than the control group (P=0.038). Average Barthel scores in the treatment group after treatment was 89.11±19.93, and in the control group 82.18±24.02 (P=0.003). NIHSS scores of the two groups after treatment decreased significantly compared with before treatment (P=0.001). Patient-reported outcomes in the treatment group were lower than the control group at day 21 and 3 months of treatment (P<0.05). There were 4 deaths, 2 in each group, and 11 adverse events, 6 in the treatment group and 5 in the control group.

CONCLUSIONThe integrative therapy combined TRABC with conventional Western treatment for HICH could promote hematoma absorption thus minimize neurologic impairment, without increasing intracerebral hematoma expansion and re-bleeding.

Blood Circulation ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Endpoint Determination ; Female ; Hematoma ; blood ; complications ; drug therapy ; Humans ; Intracranial Hemorrhage, Hypertensive ; blood ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Stroke ; blood ; drug therapy ; Treatment Outcome

OBJECTIVETo observe the clinical effect and safety of blood activating stasis removing method (BASRM) on intracerebral hemorrhage patients.

METHODSA multi-center, prospective, randomized, open, controlled and blinded endpoint design was adopted. Totally 228 intracerebral hemorrhage patients were assigned to the treatment group and the control group, 114 in each group by center randomized method. All patients received basic treatment of Western internal medicine. Patients in the treatment group received intravenous infusion with Xingnaojing Injection (XI) from the 1st day of grouping, 20 mL per day for 14 days. Then they took or were nasally fed with Chinese medical granules (by syndrome typing as complicated with wind syndrome, fire syndrome, and phlegm syndrome) for 21 days. Finally they took Naoxueshu Oral Liquid (NOL), 10 mL each time, 3 times per day till the 3rd month of incidence. Patients' disability degree, activities of daily living, neurological impairment, the effective rate, physiologic functions, mental status, social relationship, and degree of treatment satisfaction were assessed using Modified Rankin Scale (MRS), Barthel index (BI), National Institute of Health Stroke Scale (NIHSS), and patient reported outcome (PRO). Head CT was performed to evaluate the absorption of hematoma at the 1st and 7th day of grouping. The safety was also assessed.

RESULTSTotally 108 patients in the treatment group and 112 patients in the control group completed the trial. There was no statistical difference in the total effective rate between the two groups after 3 months of treatment (P>0.05). The MRS score was obviously lower in the treatment group than in the control group (P<0.01) at month 3 after attack (P<0.01). There was statistical difference in the difference between pre-post hematoma volume between the two groups after 7-day treatment (P<0.05). The NIHSS score of two groups at the 7th, 14th, 21st day, and 3rd month decreased significantly (P<0.05). Compared with the control group, the decremenit of NIHSS score decreased more obviously in the treatment group at day 7, 21, and 3rd month (P<0.05). Compared with the control group, the BI increased (P<0.01); physiologic fupctions, social relationship, treatment satisfaction and total score in PRO scale were all lower in the treatment group than in the control group (P<0.05, P<0.01). The incidence of adverse events occurred in 7 cases (6.14%) in the treatment group and 5 cases (4.39%) in the control group, with no statistical difference (P>0.05).

CONCLUSIONBASRM could lower the deformity rate of intracerebral hemorrhage patients at month 3, effectively promote hematoma absorption within 7 days, improve neurologic impairment, and elevate living abilities at month 3 of onset.

Activities of Daily Living ; Cerebral Hemorrhage ; therapy ; Hematoma ; Humans ; Medicine, Chinese Traditional ; Prognosis ; Prospective Studies ; Syndrome

AIMTo explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy.

METHODSBAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue.

RESULTSThe peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase.

CONCLUSIONThe alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.

Animals ; Brain ; enzymology ; pathology ; physiopathology ; Caspase 3 ; genetics ; metabolism ; Chronic Disease ; Evoked Potentials, Auditory, Brain Stem ; physiology ; Evoked Potentials, Somatosensory ; physiology ; Hypoxia, Brain ; physiopathology ; Male ; Maze Learning ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective To investigate the correlation between angiogenesis and tumor growth pattern as well as the lymph node metastasis to reveal the significance of vascularity in the early stage of gastric cancer.Methods 97 specimens from patients with early gastric cancer were studied by immunohistochemical method using anti-factor Ⅷ related antigen antibody.Results Microvessel count was related to tumor growth pattern. The mean vessel count was higher in superficially spreading and penetrating types of tumors. Lymph node metastasis was correlated to microvessel count. Tumors with lymph node metastasis had higher microvessel counts than those without lymph node metastasis.Conclusions In the early stage of gastric carcinoma, angiogenesis is correlated with tumor growth pattern and lymph node metastasis. Identification of tumors with high density of vascularization is beneficial for closer follow-up and adjuvant therapy.