1.Baseline Inflammatory Burden Index Predicts Primary Resistance to Combinations of ICIs With Chemotherapy in Patients With HER-2-Negative Advanced Gastric Cancer
Tingting WANG ; Huihui ZENG ; Ting HU ; Junhao ZHANG ; Zishu WANG
Journal of Gastric Cancer 2025;25(2):266-275
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.
2.Baseline Inflammatory Burden Index Predicts Primary Resistance to Combinations of ICIs With Chemotherapy in Patients With HER-2-Negative Advanced Gastric Cancer
Tingting WANG ; Huihui ZENG ; Ting HU ; Junhao ZHANG ; Zishu WANG
Journal of Gastric Cancer 2025;25(2):266-275
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.
3.Baseline Inflammatory Burden Index Predicts Primary Resistance to Combinations of ICIs With Chemotherapy in Patients With HER-2-Negative Advanced Gastric Cancer
Tingting WANG ; Huihui ZENG ; Ting HU ; Junhao ZHANG ; Zishu WANG
Journal of Gastric Cancer 2025;25(2):266-275
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.
4.SUV3 knockdown inhibits proliferation, migration, and invasion of hepatocellular carcinoma cells and induces PD-L1 expression
Junhao ZHANG ; Xiao WU ; Tingting WANG ; Zishu WANG
Chinese Journal of Hepatology 2024;32(8):734-743
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.
5.Design and application of the global health talent competency index system
Chinese Journal of Hospital Administration 2023;39(6):449-455
Objective:To establish a global health talent competency index system in China as a scientific basis for improving the global health talent team construction.Methods:Such keywords as global health, competence, global competence and public health talent competence, were used to search for literature published from 2012 to 2022 in the China National Knowledge Infrastructure database. Through literature research and job responsibility analysis and the competency iceberg theory model, the authors established the initial Index set. In October 2022, the expert consultation method was used to identify indexes, with their weight evaluated. Based on the results of expert consultation, a survey questionnaire was developed to evaluate the importance of global health talent competency indexes. A questionnaire survey was conducted in November 2022 through random convenient sampling to select relevant personnel from domestic medical institutions, universities, and pharmaceutical enterprises, and exploratory factor analysis and regression analysis on questionnaire data were made to explore the internal structure, weights and quantitative relationships between indexes of the index system.Results:The global health talent competency index system consisted of 8 level-1 indexes and 28 level-2 indexes. The 8 level-1 indexes were professional accumulation, foreign language communication, international exchange, self-management and growth, influence, achievement drive, globalization literacy, and professionalism. The weights of the level-1 indexes were 0.110, 0.104, 0.153, 0.121, 0.106, 0.171, 0.139, and 0.096, respectively. Knowledge and skill related competencies included professional accumulation and foreign language communication; Behavioral competencies included international communication, self-management and growth, and influence; Personality traits and competencies included internal drive by achievements, global literacy, and professionalism. The regression analysis results showed that all the level-2 indexes, except for creativity, team collaboration, and independent thinking, had a significant predictive effect on their level-1 indexes ( P<0.01). Conclusions:The global health talent competency index system established in this study proves scientific, and practical for the selection, training, and evaluation of global health talents.
6.Exploration on the application of standardization into the construction of modern hospital management system
Haihong YUAN ; Zishu WANG ; Yafang LI ; Ziyuan WANG
Chinese Journal of Hospital Administration 2022;38(12):877-881
Beijing Union Medical College Hospital applied the standardized management theory, focused on establishing a scientific and standardized system management mechanism, and carried out the exploration of modern hospital management standardization system construction through systematic practice. With the application of the principles of simplification, unification, coordination, optimization and competition of standardization into the construction of modern hospital management system, the basic method for the construction of standardization system was proposed based on standard system management theory. It included the standardization of system architecture, system construction process and system management mechanism. Its purpose was to effectively address the problems of the lack of systematicness, practicality and sustainability in the construction of hospital system. Importantly, the value and vitality of a system depended on its sustainable development. According to the standard system management principle of system effect, structural optimization, orderly development and circular control, the optimization of hospital system could be promoted, which is worth further practice and exploration.
7. Synergistic antibacterial effect of ursolic acid combined with fusidic acid on Staphylococcus aureus
Peng ZHANG ; Zishu WANG ; Lihong XU ; Xiangnan YIN ; Chunlin CHEN ; Wen HU
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(6):608-613
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.
8.Effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B
Wei ZHANG ; Fang SU ; Zishu WANG
Journal of International Oncology 2019;46(1):27-31
Objective To observe the effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. Methods The clinical data of 72 patients with advanced hepatocellular carcinoma associated with hepatitis B admitted to the First Affiliated Hospital of Bengbu Medical College from January 2015 to May 2017 were retrospectively analyzed. Among them,37 patients were treated with apatinib once a day,as apatinib group;35 patients were treated with FOLFOX4(oxaliplatin + calcium folinate + 5-fluorouracil)palliative chemotherapy,as FOLFOX4 group. The objective response rate(ORR),disease con-trol rate(DCR),serum alpha fetal protein(AFP),improvement of clinical symptoms,Karnofsky functional status(KPS)score improvement rate,median progression-free survival(PFS),median overall survival(OS), and the incidence of adverse reactions from both groups were contrastively analyzed. Results The ORR of apa-tinib group(27. 03% ,10 / 37)was higher than that of FOLFOX4 group(17. 14% ,6 / 35),and DCR (64. 86% ,24 / 37)was also higher than that of FOLFOX4 group(48. 57% ,17 / 35). However,there were no significant difference in ORR and DCR between the two groups(χ2 = 1. 017,P = 0. 313;χ2 = 1. 948,P =0. 163). After 16 weeks of treatment,serum AFP of apatinib group[(280 ± 20)ng/ ml]was significantly lower than that in FOLFOX4 group[(450 ± 20)ng/ ml,t = 36. 049,P < 0. 001]. Improvement rate of KPS score(86. 49% ,32 / 37)was significantly more than that of FOLFOX4 group(57. 14% ,20 / 35;χ2 = 7. 720, P = 0. 006). Improvement rate of clinical symptoms(72. 97% ,27 / 37)was significantly more than that of FOLFOX4 group(42. 86% ,15 / 35;χ2 = 6. 712,P = 0. 010). The mean PFS of apatinib group was 6. 2 months,which was significantly longer than that of FOLFOX4 group(2. 8 months,χ2 = 4. 815,P = 0. 028). The mean OS of apatinib group was 10. 9 months,which was significantly longer than that of FOLFOX4 group (6. 6 months,χ2 = 26. 429,P < 0. 001). In apatinib group,the main adverse reactions were hypertension, proteinuria and hand-foot syndrome;and in FOLFOX4 group,the main adverse reactions were leukopenia,neu-rotoxicity and liver function damage. Moreover,the adverse reactions in both groups were mostly 1 or 2 grade, which could be relieved or improved through symptomatic treatment. Conclusion Apatinib is safe and effective in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. It can significantly prolong the life of patients and improve the quality of life and the clinical symptoms of patients.
9.Inhibitory Effect of siRNA Expression Vector Inhibiting IGF2 Gene on the Proliferation of Hepatoma Cell Line Huh-7
Wei HU ; Shenglan WU ; Kuangjing WANG ; Liangpeng ZHANG ; Zishu PAN ; Shaohui TANG
China Pharmacy 2015;(22):3059-3062
OBJECTIVE:To investigate the inhibitory effect of siRNA expression vector inhibiting human insulin-like growth factor 2(IGF2)gene on the proliferation of hepatoma cell line Huh-7. METHODS:siRNA expression vector pGL3-hAFP-hTERT-siRNA3(“siRNA3”)which inhibited IGF2 gene by dual promoter regulation of recombinant human alpha-foetoprotein(hAFP)and human telomerase reverse transcriptase(hTERT)was transfected into the Huh-7 cell and normal hepatocyte L-02,and then a nega-tive control group(vector pGL3-hAFP-hTERT)and a blank control group were set up. IGF2 mRNA expression was detected by re-al-time fluorescent quantitative polymerase chain reaction 48 h after transfection into the cells in all groups;the activity of the cells by the microplate reader 0,24,48 and 72 h thereafter;and the cell cycle and apoptosis by the flow cytometer 48 h thereafter,and the changes in the protein levels of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in the cell were detected by Western blot. RESULTS:Compared with the negative control group and blank control group,IGF2 mRNA expression in the Huh-7 cell transfected with siRNA3 was obviously weaker;at 48 and 72 h after transfection,the activity of Huh-7 cell signigicantly reduced, Huh-7 cells at G1 phase obviously increased and those at S phase markedly decreased;the occurrence of early,late and total apopto-sis in Huh-7 cells apparently increased,and the protein expression of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in cells significantly weakened,with statistically significance(P<0.01 or P<0.05). No obvious change in the above-mentioned index-es could be found in L-02 cells transfected with siRNA3 expression vector (P>0.05). CONCLUSIONS:siRNA which inhibited IGF2 gene by dual promoter regulation of recombinant hAFP and hTERT can specially inhibit IGF2 gene expression and the prolifer-ation of Huh-7 cells,which may be involved with down-regulated protein expression of cell proliferation-associated gene PCNA, cell cycle control-associated genes Cyclin E2,Cyclin D2 and Cdc2 and apoptosis regulation-associated gene Bcl-2 as a result of down-regulated IGF2 mRNA expression and protein expres-sion.
10.Patterns of Lymph Node Recurrence after Radical Surgery Impacting on Survival of Patients with pT1-3N0M0 Thoracic Esophageal Squamous Cell Carcinoma.
Xiao Li CHEN ; Tian Wu CHEN ; Zhi Jia FANG ; Xiao Ming ZHANG ; Zhen Lin LI ; Hang LI ; Hong Jie TANG ; Li ZHOU ; Dan WANG ; Zishu ZHANG
Journal of Korean Medical Science 2014;29(2):217-223
The aim of this study was to investigate how patterns of lymph nodes recurrence after radical surgery impact on survival of patients with pT1-3N0M0 thoracic esophageal squamous cell carcinoma. One hundred eighty consecutive patients with thoracic esophageal squamous cell carcinoma underwent radical surgery, and the tumors were staged as pT1-3N0M0 by postoperative pathology. Lymph nodes recurrence was detected with computed tomography 3-120 months after the treatment. The patterns of lymph nodes recurrence including stations, fields and locations of recurrent lymph nodes, and impacts on patterns of survival were statistically analyzed. There was a decreasing trend of overall survival with increasing stations or fields of postoperative lymph nodes involved (all P<0.05). Univariate analysis showed that stations or fields of lymph nodes recurrence, and abdominal or cervical lymph nodes involved were prognostic factors for survival (all P<0.05). Cox analyses revealed that the field was an independent factor (P<0.05, odds ratio=2.73). Lymph nodes involved occurred predominantly in cervix and upper mediastinum (P<0.05). In conclusion, patterns of lymph node recurrence especially the fields of lymph nodes involved are significant prognostic factors for survival of patients with pT1-3N0M0 thoracic esophageal squamous cell carcinoma.
Aged
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Aged, 80 and over
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Carcinoma, Squamous Cell/mortality/pathology/*surgery
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Esophageal Neoplasms/mortality/pathology/*surgery
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Female
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Follow-Up Studies
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Humans
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Lymph Nodes/*pathology
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Recurrence, Local
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Neoplasm Staging
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Odds Ratio
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Postoperative Period
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Proportional Hazards Models
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Survival Analysis
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Tomography, X-Ray Computed

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