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.Mechanism of action of lactic acid in tumor microenvironment and related treatment
Journal of International Oncology 2022;49(6):349-352
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.
6. 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.
7.Imaging changes in brain microstructural in long-term abstinent from methamphetamine-dependence.
Lidan FAN ; Qingqing ZHANG ; Shengxiang LIANG ; Huabing LI ; Zhong HE ; Jianning SUN ; Weijun SITU ; Zhixue ZHANG ; Dawei WU ; Zishu ZHANG ; Zhifeng KOU ; Jun ZHANG ; Jun LIU
Journal of Central South University(Medical Sciences) 2019;44(5):491-500
To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.
Amphetamine-Related Disorders
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Anisotropy
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Brain
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Diffusion Tensor Imaging
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Humans
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Methamphetamine
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.Drug-eluting beads in the treatment of hepatocellular carcinoma with hepatic arterio-portal shunt
Xionghui ZHENG ; Zishu ZHANG ; Yudong XIAO ; Chunjuan CAO ; Weiqian LU
Journal of Chinese Physician 2019;21(2):220-223
Objective To investigate the safety and efficiency of drug-eluting beads (DEB) in the treatment of hepatocellular carcinoma (HCC) with hepatic arterio-portal shunt (HAPS).Methods 26 HCC patients with HAPS who underwent DEB-TACE (transcatheter arterial chemoembolization) were included in this retrospective study.Liver function level included preoperative serum albumin level,ascites,Child-Pugh classification,imaging manifestations of HAPS,follow-up and record survival time and response to cancer treatment.According to the degree of HAPS,all the patients were divided into 4 groups.After performing Kaplan-Meier,survival rate was calculated.Tumor response was measured by mRECIST criteria.Results The median survivals were 310 days,261 days,333 days,and 250 days in the entire study population,group 1,group 2,and group 3,respectively.There was no statistical significance in the survival curve among three groups (P =0.456).In the entire study population,the survival rates were 76.9%,37.3%,and 12.4% at 6 months,12 months,and 24 months,respectively.After performing proportional hazards model,the preoperative serum albumin level,presence or absence of ascites,and preoperative Child-Pugh classification were independent predict factors for prognosis.Conclusions DEB-TACE is a safe and effective treatment for HCC with HAPS.The preoperative liver function is essential for patients'prognosis.
10.The research on the technology of vacuum coating developing fingerprints and the profiling of DNA on the objects of cloth
Shuai SUN ; Zishu JIA ; Qingxia ZHANG ; Yulong HU ; Luyan XUE ; Jinjie LIU ; Li LIU ; Hui TANG
Chinese Journal of Forensic Medicine 2017;32(5):500-503
Objectives To conduct a research on the possibility and effect factors of latent fingerprints development in clothing objects after vacuum coating, and extracting fingerprints DNA and to probe in the relation among DNA template quantity and genetic loci numbers tested, and the rfu value after coating. Methods To select two groups that are free sweat hands and sweat hands and have them press their fingerprints on the cloth, after coating, and to analyze the effect of time, to quantify and test the targeted fingerprints DNA, to compare the locus numbers tested between white and black cloth. Results As the time is prolonged, the locus numbers tested decrease. The locus numbers tested on the group of sweat hands using the same method after the same placed time are lager than the free sweat hands. When the value of rfu is 600 above, the ratio of the locus numbers tested is more than 90% and the threshold of templates is 0.013ng. The locus numbers tested of white cloth is larger, comparing with black cloth when using the same method. What is more, there exists an prohibitive influence of pigments of the dyed cloth over the PCR amplification, to put it further, the loci numbers tested will be trimmed. Conclusion The technology of vacuum coating can be well used in the area of detecting fingerprint DNA.

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