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Objective To explore the value of peripheral blood circulating DNA in predicting the efficacy and prognosis of immunotherapy for advanced non-small cell lung cancer. Method A retrospective study was conducted on 78 NSCLC patients who were admitted to the Respiratory and Critical Care Medicine Department of the First Affiliated Hospital of Hebei North University and were treated with tirelizumab for advanced driver gene negativity from January 2021 to December 2021. After 2 cycles of immunotherapy, the efficacy was evaluated according to the Solid Tumor Efficacy Evaluation Criteria (RECIST 1.1), including complete remission, partial remission, disease stability, and disease progression. CR and PR patients were defined as the experimental group (n = 48) Other patients were defined as the control group (n = 30), and the ctDNA levels in peripheral blood were measured before and after treatment in both groups. ROC curves were used to analyze the predictive value of periph eral blood ctDNA levels for achieving objective remission after immunotherapy.All patients were followed up and their progression free survival were calcutated.Using univariate and multivariate regression analysis identified the factors affecting the prognosis of patients after immunotherapy. Using Spearman correlation coefficient analyzed the correlation between ctDNA levels and PFS. Kalplan Meier survival curve were used for survival analysis. Result The peripheral blood ctDNA levels before and after treatment in the experimental group were (4.47 ± 1.21)ng/μL and (2.65 ± 1.14) ng/μL, respectively (t = 7.559,P < 0.001), while those in the control group were (4.54 ± 1.15)ng/mL and (4.29 ± 1.57) ng/μL, respectively (t = 0.699,P = 0.487). There was no statistically significant difference in peripheral blood ctDNA levels between the two groups before treatment (t = -0.25,P = 0.801). The peripheral blood ctDNA levels in the experimental group decreased compared to the control group after treatment (t = -5.35,P < 0.001). The ROC curve analysis showed that the area under the curve for predicting objective remission after immunotherapy based on peripheral blood ctDNA levels was 0.819, with a sensitivity of 81.3% and specificity of 80%. Peripheral blood ctDNA levels were negatively correlated with progression free survival (r = -0.784,P = 0.000). Single factor COX regression was used to analyze the clinical and pathological characteristics and ctDNA levels of enrolled patients, and the results showed that the maximum tumor diameter was greater than 5 cm (HR = 0.501, 95% CI: 6.731 ~ 35.567) Tumor stage IV (HR = 0.392,95% CI: 0.227 ~ 0.677), treatment approach (HR = 15.473,95% CI: 6.731 ~ 35.567), and ctDNA levels (HR = 4.657,95% CI: 3.182 ~ 6.555) are all influencing factors for PFS in advanced NSCLC patients after immunotherapy. Multiple factor analysis was conducted on the appeal indicators with statistical differences, and the results showed that treatment approach (HR = 2.981,95% CI:1.019 ~ 8.722) and peripheral blood ctDNA levels (HR = 3.918,95% CI: 2.619 ~ 5.861) It is an independent influencing factor of PFS in advanced NSCLC patients. The Kalplan Meier survival curve was used for analysis, and the results showed that the median PFS of the treatment effective group was 8.4 months, while the median PFS of the control group was 5.4 months. (χ² = 49.277, P = 0.000). Conclusion Immunotherapy combined with chemotherapy can enhance the ability to kill tumor cells, and peripheral blood ctDNA levels can evaluate the efficacy and prognosis of immunotherapy, which can be used to guide immunotherapy in advanced NSCLC patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the application value of prognostic nutritional index and urea/creatinine ratio in nutritional status assessment for patients with esophageal cancer undergoing radiotherapy and chemotherapy. Methods A total of 138 patients with esophageal cancer who received radiotherapy and chemotherapy were screened. NRS 2002 nutritional screening was used as the standard. Prognostic nutritional index (PNI) and urea/creatinine ratio (UCR) were used to evaluate the malnutrition of patients with esophageal cancer. ROC curve was used to evaluate and compare the diagnostic efficacy of different nutritional screening tools. Results The biochemical and hematological indexes of patients with esophageal cancer showed certain characteristics, in which the levels of urea, creatinine, UCR, ALB, PALB, TP, TC, TG, HDL and LDL all fluctuated within the normal range. In terms of nutritional risk screening, the NRS 2002 score identified nutritional risk in 57.97% of patients, while the PNI and UCR predicted nutritional risk in 31.16% and 40.58% of patients, respectively. Consistency test showed that the Kappa value of PNI and NRS 2002 scores was 0.460 (P < 0.05), and the Kappa value of UCR and NRS 2002 scores was 0.522 (P < 0.05), indicating that there was a certain correlation between them and NRS 2002 scores in nutritional risk screening. Correlation analysis showed that NRS 2002 score was significantly correlated with UCR, ALB, PALB, PBL, Cr, HDL and TP (P < 0.05), while PNI was significantly correlated with ALB, PALB, PBL, Cr, HDL, TP and UREA (P < 0.05) . There were significant correlations between UCR and PALB, UREA and Cr (P < 0.05) . Logistic univariate regression analysis further confirmed these correlations and revealed that malnutrition was negatively correlated with albumin, prealbumin, total protein, lymphocytes, creatinine and BMI, and positively correlated with urea. However, multivariate regression analysis did not find any statistical difference between these related factors and the two objective evaluation measures. The results of diagnostic efficacy evaluation showed that the area under ROC curve of PNI and UCR evaluation to predict esophageal cancer malnutrition was 0.779 and 0.736, respectively, with statistical significance (P < 0.001) . Among them, UCR showed higher sensitivity and PNI showed higher specificity, but there was no significant difference in diagnostic value between them. Conclusion PNI and UCR as nutritional assessment tools have certain application value in the nutritional risk screening of patients with esophageal cancer, but their consistency with NRS 2002 score needs to be improved. When assessing the nutritional status of patients, a combination of various indicators and methods should be used to achieve more accurate diagnostic results. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate the neuroprotective effect of microglia polarization mediated by Raf kinase inhibitor protein (RKIP) intracerebral hemorrhage (ICH) model. Methods Forty-eight adult male Sprague-Dawley (SD) rats were randomly divided into three groups: the Sham + Vector group, the ICH + Vector group, and the ICH + RKIP group, with 16 rats in each group. The collagenase ICH model was established in ICH+Vector group and ICH + RKIP group. Before operation and 1, 3, 5, and 7 days after operation, 8 animals in each group were tested for behavior. Apoptosis of neurons was detected by flow cytometry. Seven days after ICH, the expressions of RKIP, p-p65, and TRAF6 around hematoma were analyzed by protein blot. Results Compared with ICH + Vector group, rats in ICH + RKIP group need less time to find the platform, spend longer time in the target quadrant, and significantly reduce the times of crossing the platform (P < 0.05) . The number of Nissl corpuscles in ICH + RKIP group was significantly higher than that in ICH + Vector group (P < 0.05) . In addition, the number of neuronal apoptosis in ICH + RKIP group was significantly lower than that in ICH + Vector group (P < 0.05) . Compared with Sham group, rats receiving ICH showed a gradual decrease in RKIP expression, and reached the lowest value on the 7th day (P < 0.05) . Seven days after ICH, the expression of RKIP protein in hematoma of rats in ICH + RKIP group was significantly higher than that in ICH + Vector group (P < 0.05), and the expression of p-p65 and TRAF6 protein was significantly lower than that in ICH + Vector group (P < 0.05) . Compared with ICH + Vector group, the number of iNOS + Ibal1+ cells in ICH + RKIP group decreased significantly (P < 0.05), while the number of Arg-1 + Ibal1+ cells increased significantly (P < 0.05) . Conclusion Up-regulation of RKIP promotes functional recovery after ICH, and its mechanism involves inhibiting TRAF6/NF-kB signaling pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the protective effect of target temperature management based different durations with delayed hypothermia for traumatic brain injury(TBI) in rats. Methods 36 healthy adult male SD rats were randomly divided into NT group, HT4h group, HT24h group and HT48h group. The TBI model of rats was prepared with an electronic controllable cortical injury device. NT group was treated with normal temperature (37 ) 4 h after TBI, and the experimental groups were treated with low temperature (33.0 ± 1.0 ) 4 h after TBI for 4 h, 24 h, and 48 h. Three days after TBI, the motor function of the rats in each group was evaluated by beam walking test and inclined-grid climbing test, EB staining was used to measure the blood-brain barrier permeability, the change of hippocampal neurons was observed by Nissl staining, the expression of DCX and GFAP was detected by immunofluorescence, and the expression of Bcl-2 and Bax was measured by Western blot and immunohistochemistry. Results Compared with NT group, the experimental groups could significantly improve the motor function of TBI rats, reduce the permeability of blood-brain barrier,protect hippocampal neurons, promote DCX expression, inhibit GFAP expression, up-regulate the expression of Bcl-2 protein, and down-regulate the expression of Bax protein. However, the protective effect was more apparent in HT48h group than other experimental groups (P < 0.05). Conclusion Long-term delayed target temperature management has a significant brain protective effect. [ABSTRACT FROM AUTHOR]

Objective To investigate the role and mechanism of Rho-related GTP-binding protein F (RhoF)-mediated Th17 polarization in the development of severe acute pancreatitis (SAP). Methods RhoF transgenic mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10), and WT mice were randomly divided into control group (n = 10), SAP group (n = 10) and SAP+Y-27632 group (n = 10). SAP models were established in all groups except the control group. The SAP+Y-27632 group was infused with Y-27632 via tail vein after model establishment. T cells in mouse blood samples were isolated for RhoF, p-MYPT1 protein detection and ROCK activity determination, and the percentage of lymphoid CD4+T cells producing IL-17 was analyzed by flow cytometry. Results The expression of RhoF and p-MYPT1 was increased in T cells in the SAP group compared with that in the control group (P < 0.01), and the level of RhoF was closely correlated with that of p-MYPT1 (P = 0.018). The expression of RhoF protein level in T cells of mice in the RhoF group increased by approximately 30% compared to that in the WT group, and the level of spontaneous IL-17 production by CD4+ T cells was significantly increased (P = 0.003). Compared with WT mice, the histological score of pancreatic injury, the expression of RhoF and p-MYPT1 in T cells, the number of IL-17+ T cells and serum IL-17 level in RhoF transgenic mice were significantly increased (P < 0.05). The histological score, RhoF and p-MYPT1 expression of T cells, IL-17+ T cell numbers and serum IL-17 level were significantly lower in the SAP+Y-27632 group than those in the SAP group (P < 0.05). Conclusion RhoF/ROCK signaling pathway-mediated polarization of Th17 cells is involved in the pathogenesis of SAP. [ABSTRACT FROM AUTHOR]

Metastatic pheochromocytoma and paraganglioma (MPPGL) is a rare neuroendocrine tumour in which genetic factors play an important role. In recent years, with the continuous progress of genetic testing technology, more and more susceptibility genes have been proved to be associated with MPPGL, making early identification of MPPGL possible. Recent studies have shown that genes associated with the development of MPPGL include SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, MDH2, VHL, IDH1, PDH1/2, SLC25A11, GOT2, DLST, CSDE1, MAML3, H3F3A, MERTK, PCDHGC3, and KIF1B, with SDHA, SDHB, SDHC, SDHD, and SDHAF2 being the common pathogenic genes. Potential mutations affect the clinical manifestations of MPPGL, such as malignant potential and genetic prediction, which can help to better understand the clinical course and treat accordingly. Genetic testing for pheochromocytomas and paragangliomas allows for early detection of genetic syndromes and facilitates close follow-up of high-risk patients. This article provides a review of the progress of research on susceptibility genes identified in MPPGL in recent years, with a view to providing a certain theoretical basis for further related research. [ABSTRACT FROM AUTHOR]

Central nervous system(CNS)is a complex system closely related to anesthesiology. The molecular biological mechanisms of many CNS diseases were not exactly clear. Long noncoding RNA(lncRNA) H19 is abundant in human brain and plays an important role in the regulation of various CNS diseases. Besides, lncRNA H19 is also involved in the mechanism of several anesthetics. In this review, we emphasized the role and addressed the specific mechanisms of lncRNA H19 in CNS diseases and anesthetics, hoping to provide a new theoretical basis for future researches. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship between SIRT1 genetic variation (rs1467568, rs4746720) and microscopic polyangiitis (MPA) in Guangxi population. Methods The SIRT1 polymorphisms of 208 patients with microscopic polyangiitis (MPA) and 211 healthy volunteers were genotyped by multiplex polymerase chain reaction (PCR) and high throughput sequencing. The allele frequencies and genotypes were compared. The linkage disequilibrium, haplotype and genetic model were analyzed. The relationship between different genotypes and clinical symptoms and laboratory biochemical indexes was evaluated. Results The results showed no significant difference between the two groups in genotype, allele frequency, and haplotype of SIRT1 rs1467568 and rs4746720(P > 0.05). In the age group ≥ 54 years old, the dominant model(OR = 0.50,95%CI: 0.27 ~ 0.92, P = 0.026), overdominant model(OA = 0.49,95%CI: 0.26 ~ 0.92, P = 0.026) and additive model (OR = 0.57, 95%CI: 0.33 ~ 0.99, P = 0.045) of SIRT1 rs1467568 were associated with lower susceptibility to MPA. In rs1467568, MPA patients with GG genotype had higher levels of glutamic pyruvic transaminase (P = 0.012), while in rs4746720, MPA patients with TT and TC genotypes had higher levels of glutamic oxaloacetic transaminase (P = 0.036). Conclusions In this study, SIRT1 rs4746720 was not related to the susceptibility to MPA in Guangxi population, but rs1467568 may be associated with the susceptibility to MPA in some people (5 54 years old) in Guangxi, and rs1467568 and rs4746720 were associated with the levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in patients with MPA. [ABSTRACT FROM AUTHOR]

Objective To observe the expression of fructose-bisphosphate aldolase C (ALDOC) in colon cancer tissues and cells and to explore its effect on biological behavior. Methods GEPIA database was used to analyze the expression level of ALDOC in colon cancer tissues. The expression of ALDOC mRNA and protein in colon cancer tissues and cancer cells SW620, SW480, HT-29 and HCT-116 were detected by RT-qPCR and immu-nohistochemistry, and the relationship between ALDOC mRNA expression and clinicopathological factors was analyzed. Colon cancer cell SW620 was divided into control group, NC inhibitor group and ALDOC inhibitor group. ALDOC inhibitor or negative control was transfected into SW620 cells by lentivirus transfection kit. MTT assay and monoclonal formation of cancer cells were used to detect cell proliferation. Scratch test was used to detect cell migration ability, and transwell chamber test to detect the invasion ability of cells. The expression of ALDOC mRNA was detected by RT-qPCR, and that of ALDOC and MMP-2/9 was detected by western blot. Results GEPIA database showed that the expression level of ALDOC in colon cancer tissues was higher than that in normal tissues (P < 0.05). Compared with those in adjacent tissues or FHC, ALDOC mRNA and protein in colon cancer tissues and cells SW620, SW480, HT-29 and HCT-116 were up-regulated, and ALDOC mRNA level was significantly correlated with tumor differentiation, TNM stage and lymph node metastasis (P < 0.05). Down-regulating ALDOC mRNA could down-regulate MMP-2 and MMP-9 protein levels, inhibit cell growth, and reduce the number of wound healing and invasive cells (P < 0.05). Conclusion ALDOC level is up-regulated in colon cancer tissues and cells, and it is closely related to the poor prognosis of colorectal cancer patients. ALDOC regulates the invasion and migration of colon cancer cells by regulating MMP-2/9. [ABSTRACT FROM AUTHOR]