Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

Purpose: Combinations of immune checkpoint inhibitors (ICIs) and chemotherapy have become the standard first-line treatment for human epidermal growth factor receptor 2 (HER-2)-negative advanced gastric cancer. However, primary resistance remains a challenge, with no effective biomarkers available for its prediction. This retrospective study explores the relationship between the baseline inflammatory burden index (IBI) and primary resistance in such context. Materials and Methods: We analyzed 62 patients with HER-2-negative advanced gastric cancer who received ICIs and chemotherapy as their first-line treatment. The IBI was calculated as follows: C-reactive protein (mg/L) × neutrophil count (10 3 /mm 3 )/lymphocyte count (10 3 /mm 3 ). Based on disease progression within 6 months, patients were categorized into the primary resistant or the control group. We compared baseline characteristics and IBI scores between the groups and assessed the predictive value of the IBI using the receiver operating characteristic curve. Both univariate and multivariate binary logistic regression analyses were conducted to identify factors influencing primary resistance. Results: Nineteen patients were included in the primary resistance group, and forty-three patients were included in the control group. The IBI was significantly higher in the resistant group compared to the control group (P<0.01). The area under the curve for the IBI was 0.82, indicating a strong predictive value. Multivariate analysis identified the IBI as an independent predictor of primary resistance (P=0.014). Conclusions The baseline IBI holds promise as a predictor of primary resistance to combined ICIs and chemotherapy in patients with HER-2-negative advanced gastric cancer.

Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.

Objective:To explore expression and prognostic value of oncostatin M(OSM)in endometrial cancer and to analyze relationship between OSM expression and immune cell infiltration in endometrial cancer tissues.Methods:OSM expression in pan-can-cer was analyzed by TIMER database,OSM expression in endometrial cancer and normal tissues was compared,and survival analysis for patients with different OSM expression was performed;relationship between OSM expression and immune cell infiltration was analyzed by TIMER and TISIDB,and ssGSEA algorithm was used to calculate difference in abundance of immune cell infiltration in samples with different OSM expression;GSEA software was applied to perform enrichment analysis;clinical tissue samples were collected for validation.Results:OSM expression was higher in endometrial cancer tissues than that in normal endometrial tissues(P=4.1e-28),and endometrial cancer patients with high OSM expression had prolonged recurrence-free survival(RFS)(P=0.004 8).OSM expression was positively correlated with abundance of immune cell infiltration and genetic markers of immune cells(P<0.05).OSM was mainly enriched in immune-related signaling pathways.OSM expression was higher in endometrial cancer tissues than normal and atypical hyperplastic tissues(P=0.016 9).Proportions of immune cell markers CD4,CD8,and CD68 were increased in tumor tissues with high OSM expression(all P<0.05),which were positively correlated with OSM expression.Conclusion:OSM is highly expressed in endometrial cancer tissues and correlated with prognosis;OSM expression is positively correlated with immune cell infiltration level and can be used as a biomarker for immunotherapy and prognosis.

Cases of human infection with H7 subtype avian influenza virus(AIV)combined with five NA subtypes(N2,N3,N4,N7,and N9)have been reported.This study was aimed at establishing a method for simultaneous detection and dif-ferential diagnosis of H7 and five NA subtypes of AIV.Seven pairs of specific primers were designed according to the conserved sequences of the HA gene of H7 subtype AIV,the NA gene of five NA AIV subtypes,and the M gene of all AIV subtypes.A high-throughput GeXP typing method was established for simultaneous detection of the H7 subtype and the five NA subtypes of AIV by using GeXP multiple gene expression and capillary electrophoresis analysis technology.The specificity and sensitivity of the method were determined,and clinical samples were tested.The specificity results indicated that this method was able to simultaneously detect seven target genes in a single tube;each pair of specific primers was able to detect the corresponding AIV subtype,and the universal detection primers were able to detect all subtypes of AIV,with no cross-reaction with other common avian disease pathogens.Sensitivity results demonstrated that this method was able to simultaneously detect seven target genes with a threshold detection limit was 100 copies/μL.The detection results for 150 clinical samples were consistent with those of viral isolation and identification.The high-throughput GeXP method for simultaneous differential diagnosis of the H7 subtype and five subtypes of AIV established in this study has advantages of high specificity,high sensitivity,rapidity,and simplicity,thus providing a new detection method for the effective prevention and control of AIV.

Objective:To evaluate the efficacy and side effects of venetoclax combined with azacitidine chemotherapy in the treatment of previously untreated adult patients with acute myeloid leukemia(AML).Methods:A retrospective analysis was performed on 48 untreated adult AML patients admitted to the Department of Hematology,Affiliated Hospital of Jinggangshan University from January 2020 to December 2022.Among them,26 patients received venetoclax combined with azacitidine chemotherapy(observation group),and 22 patients received daunorubicin plus cytarabine chemotherapy(control group).The differences in complete response(CR)rate,objective response rate(ORR),progression-free survival(PFS),overall survival(OS)and adverse reactions(AR)were compared between the two groups.Results:There was no significant difference in age,sex ratio,absolute value of tri-lineage cell and proportion of bone marrow primordial cells between the two groups before treatment(all P＞0.05).The CR rate and the ORR rate of the observation group was significantly higher than that of the control group(P＜0.05).After treatment,there were no significant difference in the adverse reactions such as myelosuppression,granulocytosis,secondary infection,mucosal damage,liver and kidney damage,cardiotoxicity and gastrointestinal toxicity between the two groups(P＞0.05).The median PFS and the median OS of the observation group were significantly better than those of the control group(P＜0.05).Conclusion:The remission rate of venetoclax combined with azacitidine was higher than that of conventional chemotherapy in previously untreated adult acute myeloid leukemia.Venetoclax combined with azacitidine chemotherapy could reduce hematologic related side reactions and prolong the remission period and survival of AML patients.

Objective To explore the dilemmas faced by surrogate decision-makers of severe stroke patients in treatment decision-making,and to provide a basis for developing decision support strategies.Methods From April to December 2023,through phenomenological qualitative research with 16 surrogate decision-makers with severe stroke patients from ICU of the department of neurology in a tertiary hospital in Jing'an District,Shanghai.semi-structured in-depth interviews were used to examine the perceptions of decision-making on surrogate.Data were analyzed via Braun's style of thematic analysis.Results 4 themes and 10 sub-themes were identified.Theme 1:negative emotional dilemmas(urgent decision-making leads to anxiety,fear,and unknown stroke trajectory increases the sense of uncertainty).Theme 2:supportive environment dilemmas(lack of information support delays decision-making;lack of family support increases decision-making stress;insufficient economic support increases the burden of decision-making).Theme 3:the dilemma of weighing the pros and cons(difficult trade-offs between risk and reward,tough decisions between reality and ethics,conflicting choices of life and dignity).Theme 4:preference management dilemmas(practical difficulties in adhering to patient preferences,impediments to decision-making due to unknown patient preferences).Conclusion Surrogate decision-makers of severe stroke patients face multiple decision-making dilemmas.Healthcare professionals should provide emotional support in multiple ways and comprehensive support to reduce the decision-making dilemmas experienced by surrogate decision-makers,as well as implement death education for surrogate decision-makers and promote advance care planning to reduce their decision-making stress.

Objective To explore the mechanism of intervention of phosphatidylinositol 3-kinase/nerve growth factor/vanilloid receptor 1(NGF/PI3K/TRPV 1)signaling pathway.Methods Forty 10 SPF SD male rats were selected,including 10 in blank group,13 in model group,7 in study 1 and 9 in study 2.The control group and model group will only receive saline ingavage without any other treatment.Study group 1 received 20 mg/kg aqueous solution for gavage,and study 2 group gave 4 g/kg for gavage.The Bristol score,the spleen coefficient and thymus coefficient were analyzed,and the expression levels of IgA,IgG,IgM,IL-1 β,IL-6,TNF-α and NGF/PI3K/TRPV 1 protein expression were measured.Results Compared with the blank group,Bristol score,IgA,IgG,IgM,IL-1 β,IL-6,TNF-α were increased(P＜0.05),Bristol score,spleen coefficient,thymus coefficient,IgA,IgG,IgM,IL-1 β,IL-6,TNF-α levels and NGF,PI3K,and TRPV 1 were decreased(P＜0.05).Conclusion Shenling powder inhibited NGF/PI3K/TRPV 1 pathway,improved gastrointestinal function and stool state,reduced inflammation,and improved the homeostasis of immune function,with remarkable intervention effect.