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.

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.

Objective To clone the glycosyltransferase gene UGT708Z1 in Anemarrhena asphodeloides and perform its bioinformatics analysis,prokaryotic expression analysis and functional characterization.Methods A candidate glycosyltransferase gene UGT708Z1 was mined and screened out from Anemarrhena asphodeloides based on the transcriptome data.According to its full-length open reading frame,the specific primers with homologous arms were designed.Subsequently,the UGT708Z1 gene was cloned by PCR.The prokaryotic expression recombinant vector pET-32a(+)-UGT708Z1 was constructed through homologous recombination technology,and the soluble target protein was obtained by prokaryotic expression and purified protein technology.Finally,the function of UGT708Z1 was identified through enzymatic reaction in vitro.Results Sequence analysis showed that the open reading frame of UGT708Z1 was 1377 bp,encoding 458 amino acids.The result of prokaryotic expression showed that UGT708Z1 successfully expressed the soluble target protein,and the purified recombinant protein was 70.86 kDa.The results of enzymatic reaction in vitro showed that UGT708Z1 had flavonoid 7-OH glycosylation activity and could catalyze icaritin to produce icariside I.In addition,UGT708Z1 also possessed the activities of catalyzing the 7-O-glycosylation of quercetin and apigenin.Conclusion In this study,a flavonol glycosyltransferase UGT708Z1 was successfully cloned and identified from Anemarrhena asphodeloides,which would lay a foundation for further analysis of flavonol glycosides biosynthesis.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective To clone the glycosyltransferase gene UGT708Z1 in Anemarrhena asphodeloides and perform its bioinformatics analysis,prokaryotic expression analysis and functional characterization.Methods A candidate glycosyltransferase gene UGT708Z1 was mined and screened out from Anemarrhena asphodeloides based on the transcriptome data.According to its full-length open reading frame,the specific primers with homologous arms were designed.Subsequently,the UGT708Z1 gene was cloned by PCR.The prokaryotic expression recombinant vector pET-32a(+)-UGT708Z1 was constructed through homologous recombination technology,and the soluble target protein was obtained by prokaryotic expression and purified protein technology.Finally,the function of UGT708Z1 was identified through enzymatic reaction in vitro.Results Sequence analysis showed that the open reading frame of UGT708Z1 was 1377 bp,encoding 458 amino acids.The result of prokaryotic expression showed that UGT708Z1 successfully expressed the soluble target protein,and the purified recombinant protein was 70.86 kDa.The results of enzymatic reaction in vitro showed that UGT708Z1 had flavonoid 7-OH glycosylation activity and could catalyze icaritin to produce icariside I.In addition,UGT708Z1 also possessed the activities of catalyzing the 7-O-glycosylation of quercetin and apigenin.Conclusion In this study,a flavonol glycosyltransferase UGT708Z1 was successfully cloned and identified from Anemarrhena asphodeloides,which would lay a foundation for further analysis of flavonol glycosides biosynthesis.

Objective:To analyze the data changes of tertiary hospitals,secondary hospitals and primary healthcare institutions in Shandong before and after the reform of Dignosis Related Group(DRG)/Diagnosis-Intervention Packet(DIP)payment method,and to explore the impact of the reform of DRG/DIP payment method on the effect of hierarchical diagnosis and treatment.Methods:Data were collected from 16 cities in Shandong Province for a total of 18 quarters in the first half of 2019-2023,including the percentage of expenditure of the health insurance fund,the percentage of discharges,and the sub-average hospitalization cost.Spatial panel models were constructed to conduct σ-convergence and absolute β-convergence analyses.Results:The convergence analysis showed that the inter-regional differences in the percentage of discharges,the percentage of fund expenditure and the average hospitalization cost of tertiary medical institutions were reduced;the regression coefficients of the three indicators in the absolute convergence analysis were significantly negative(β＜0,P＜0.01),indicating that the level of hierarchical diagnosis and treatment in various cities and regions has been equalized.Conclusion:The reform of DRG/DIP payment method reform has effectively optimized the allocation of medical resources in Shandong and reduced regional differences.It is needed to strengthen the effect of the payment method reform,reinforced the incentive of primary care and construct a full-cycle health management-oriented health insurance system in the future.

Objective:To study the SUV3 gene role during the process of occurrence and advancement of hepatocellular carcinom.Methods:The The differences in SUV3 expression between hepatocellular carcinoma tissues and normal liver tissues were compared by analyzing transcriptome sequencing data from TCGA and GTEx databases. SUV3 knockdown in different hepatocellular carcinoma cells was performed using RNA interference technology. Overexpression vectors were constructed to overexpress SUV3 in different hepatocellular carcinoma cells. The SUV3 regulatory effect was studied on proliferation, migration, and invasion of hepatocellular carcinoma cells. A subcellular fraction isolation approach was used to investigate whether SUV3 knockdown resulted in the release of mitochondrial DNA into the cytoplasm. Quantitative reverse transcription PCR was applied to investigate whether SUV3 knockdown affected PD-L1 expression. The two groups were compared using a two-tailed t-test. Results:The TCGA database analysis revealed that SUV3 expression was higher in hepatocellular carcinoma tissues than in normal liver tissues, and the prognosis of patients with high SUV3 expression in hepatocellular carcinoma tissues was poor. The quantitative RT-PCR results showed that SUV3 expression was higher in hepatocellular carcinoma tissues than that in paracancerous liver tissue. The MTS assay showed that with SUV3 knockdown, the proliferation rate was significantly lower in hepatocellular carcinoma cells than that of the control hepatocellular carcinoma cells ( P<0.01). The proliferation rate was significantly higher in SUV3-overexpressed hepatocellular carcinoma cells than that of control hepatocellular carcinoma cells ( P<0.01). Cell scratch assay and cell migration and invasion assay showed that SUV3 knockdown inhibited the migration and invasion of hepatocellular carcinoma cells ( P<0.01), while SUV3 overexpression promoted the migration and invasion of hepatocellular carcinoma cells ( P<0.05). SUV3 Knockdown led to a decrease in the overall level of mtDNA ( P<0.01) in accompanied by an increase in mtDNA level in the cytoplasm ( P<0.01), indicating that SUV3 knockdown led to mitochondrial DNA leakage into the cytoplasm. SUV3 knockdown resulted in elevated PD-L1 expression ( P<0.001), and overexpression of TREX1 in SUV3 knockdown cells decreased mtDNA levels in the cytoplasm and inhibited SUV3 knockdown, resulting in elevated PD-L1 expression, indicating that SUV3 knockdown induced PD-L1 expression by increasing cytoplasmic DNA levels. Conclusions:The SUV3 gene may play an oncogenic function in hepatocellular carcinoma cells.

AIM: To explore the antibacterial activity and underlying mechanism of ursolic acid combined with fusidic acid against Staphylococcus aureus (SA) ATCC29213 and Methicillin-Resistant Staphylococcus aureus (MRSA) ATCC43300 in vitro. METHODS: The minimum inhibitory concentration (MIC) of the combined use of ursolic acid and fusidic acid on SA, MRSA was determined by the micro broth dilution method and the micro checkerboard method, and the partial inhibitory concentration index (FICI) was calculated to determine the combined effect. And the bactericidal effect of fusidic acid combined with ursolic acid was studied by the time-killing curves. The agar double dilution method was used to determine the anti-drug resistance mutation concentration (MPC) and anti-drug resistance mutation selection window (MSW) of fusidic acid alone and in combination with ursolic acid. The viable count of biofilm carrier were determined by serial dilution method and the semi-quantitative biofilm by crystal violet staining method. RESULTS: The combined use of ursolic acid and fusidic acid for SA and MRSA FICI were 0.312 5 and 0.375, respectively. The time-killing curve showed that 1MIC ursolic acid combined with 1MIC fusidic acid has a synergistic bactericidal effect on SA and MRSA. The MPC of fusidic acid to MRSA was 256 μg/mL and the MSW was 256. After fusidic acid combined with ursolic acid, the MPC decreased to 8 μg/mL. The combined group was significantly reduced compared to the fusidic acid group. The semi-quantitative and biofilm bacterial counts of combined group were markedly decreased compared to the fusidic acid group after the biofilm cultivate for 48 h and 72 h.CONCLUSION: The combined use of UA and FA has a synergistic effect on SA and MRSA.

Lactic acid, a widespread metabolite in the tumor microenvironment, is mainly produced by tumor cells that undergo aerobic glycolysis. Lactic acid is closely related to the occurrence and development of tumor. It not only serves as a substrate to supply energy to tumor cells, but also acts as a signaling molecule to activate multiple pathways to promote invasive and metastasis, angiogenesis and immune escape of tumor cells. In-depth research on the mechanism of action of lactic acid in the occurrence and development of tumor and related therapeutic progress will help to find drug targets for treatment of tumor and improve prognosis of patients.