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Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRASG12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.
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Eosinophil extracellular traps (EETs), an important pathway of eosinophil to exert its effects, are composed of DNA fibers, histone and eosinophil granule proteins. Recently, many researches have shown that EETs play an important role in the genesis and development of respiratory diseases including asthma, allergic bronchopulmonary aspergillosis and chronic obstructive pulmonary disease. EETs can directly damage airway epithelial cells, promote airway inflammation and airway hypersecretion, increase the stickiness of secretions and induce the generation of autoantibody, helping eosinophils and their products participate in a cascade of events leading to inflammation and disease. Researches on EETs can also be helpful in investigating new targets for the treatment of chronic airway diseases.
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Objective:To study the efficacy and safety of EndoClot polysaccharide hemostatic system (EndoClot PHS) for heparinized arterial hemorrhage of upper digestive tract (Forrest Ⅰa) in animal model.Methods:Twelve experimental pigs were randomly divided into the test group ( n=6) and the control group ( n=6) by simple random grouping method. Gastric arterial hemorrhage models were established. Endoclot PHS and Hemospray were used to spray on the wound to stop bleeding in the test group and the control group respectively. The time of effective hemostasis, the amount of hemostatic particles used, and the blockage of the powder feeding tube and its replacement were compared between the two groups. The survival and complications of experimental pigs were observed after the operation. In 10 days after the operation, the experimental pigs were euthanized for pathological dissection. Results:Spurting or pulsatile bleeding was achieved in all experimental pigs. There were significant differences in the time of effective hemostasis (8.75±0.84 min VS 9.83±0.62 min, t=-2.53, P=0.030) and the amount of hemostatic particles used to achieve effective hemostasis (6.71±0.39 g VS 14.10±1.62 g, t=-10.86, P<0.001) between the test group and the control group. There was no significant difference in the occurence of clogging or the replacement of powder feeding pipes between the two groups (0.64±0.02 times VS 0.67±0.04 times, t=-1.64, P=0.131). In addition, the gas source of the test group was stable, and the visual field under the endoscope was clear. Neither the test group nor the control group had gastric lesions, perforation, or embolism. The blood glucose, blood routine, and liver and kidney functions were normal, and no thrombosis or embolism of the main organs occurred in either group. Conclusion:EndoClot PHS is safe and effective for heparinized upper gastrointestinal arterial hemorrhage (Forrest Ⅰa) in animal models.
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Objective:To study the clinical characteristics and classification of gastric neuroendocrine neoplasm(NEN) and prognostic factors of mixed adenoneuroendocrine carcinoma (MANEC) and gastric neuroendocrine carcinoma(NEC).Methods:A total of 148 gastric NENs were divided into type Ⅰ, type Ⅱ and type Ⅲ based on the classification of European Neuroendocrine Tumor Society (ENETS). Kaplan-Meier test and Cox regression model were used in univariate and multivariate survival analysis in 108 cases with pathological G3 gastric NEN.Results:In this study, the percentages of type Ⅰ, type Ⅱ and type Ⅲ were 25.0%(37), 3.4%(5) and 71.6%(106) respectively. Among type Ⅰ patients, 28(75.7%) lesions were located in gastric fundus or body, 29(78.4%) had bumps. Lymph node involvement was found in 4 (10.8%) patients. Twenty-six (70.3%) patients received endoscopic treatment and 11 (29.7%) with surgery. All 5 type Ⅱ patients presented lesions in gastric fundus or body, including 4 with ulcers, who were all treated by endoscope. Three type Ⅱ patients had gastrinoma, and 2 combined with multiple endocrine neoplasmⅠ. In type Ⅲ patients, 56(52.8%) showed ulcerative lesions. The majority of patients (102, 96.2%) had a single lesion, 94(88.7%) with lymph node or other organ metastasis. In this study, no deaths were reported in gastric NEN with a pathological grade of G1 or G2. The mortality rate was 38.9%(42/108) in patients with G3 NEN. Survival analysis suggested that age, metastasis of tumor were associated with poor prognosis ( P=0.041, 0.025). Conclusions:Patients with gastric NEN have heterogenous clinical presentations according to gender, age, endoscopic features, infiltration and metastasis, and pathological grade. Aging and metastasis are negative prognostic factors of G3 gastric NEN.