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.ResNet-Vision Transformer based MRI-endoscopy fusion model for predicting treatment response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A multicenter study.
Junhao ZHANG ; Ruiqing LIU ; Di HAO ; Guangye TIAN ; Shiwei ZHANG ; Sen ZHANG ; Yitong ZANG ; Kai PANG ; Xuhua HU ; Keyu REN ; Mingjuan CUI ; Shuhao LIU ; Jinhui WU ; Quan WANG ; Bo FENG ; Weidong TONG ; Yingchi YANG ; Guiying WANG ; Yun LU
Chinese Medical Journal 2025;138(21):2793-2803
BACKGROUND:
Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment.
METHODS:
In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model.
RESULTS:
The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set.
CONCLUSION
The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans
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Rectal Neoplasms/diagnostic imaging*
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Magnetic Resonance Imaging/methods*
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Male
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Female
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Middle Aged
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Neoadjuvant Therapy/methods*
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Aged
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Adult
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Chemoradiotherapy/methods*
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Endoscopy/methods*
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Treatment Outcome
6.Types of Major Microorganisms in Pharmaceutical Water Systems and Control Measures
Yinghong LI ; Linshuang ZHANG ; Jue LI ; Xiaoling ZHENG ; Zhengnan WANG ; Yinhuan WANG ; Junhao CHEN ; Liang HONG ; Qiaofeng TAO ; Huan CHEN
Chinese Journal of Modern Applied Pharmacy 2024;41(3):415-419
OBJECTIVE
To analyze the types and control measures of major microorganisms in pharmaceutical water systems, so as to provide guidance for effective control of pharmaceutical water systems.
METHODS
The main microbial species, abundance and harmfulness of drinking water, purified water and water for injection were reviewed, and the control measures on microorganisms in pharmaceutical water were discussed.
RESULTS
There were differences in the main microbial types in pharmaceutical water. Burkholderia cepacia complex and Ralstonia pickettii were conditioned pathogens in pharmaceutical water, thus causing certain biological safety hazards.
CONCLUSION
Pharmaceutical companies can strengthen the control of microorganisms in the water system by establishing microbial databases and common microbial strain banks at all levels. Trend analysis should to be conducted based on alert limits and action limits, so as to strengthen the control of microorganisms in the water system.
7.Study on the potentiation effect of Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma on PNS in the improvement of blood-brain barrier damage in MCAO rats based on the opening and closing of sweat pores
Linyao HAO ; Shuangyang LI ; Junhao REN ; Xiaoqiang WANG ; Lingxue WANG ; Dechou ZHANG ; Hongmei TANG ; Xue BAI
International Journal of Traditional Chinese Medicine 2024;46(8):1006-1014
Objective:To observe the neuroprotective effect of wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) in combination with Panax ginseng total saponin (PNS) on cerebral ischemia-reperfusion rats; To elucidate the mechanism of "wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group, model group, PNS group, Puerariae Lobatue Radix group, Acori Tatarinowii Rhizoma group, Puerariae Lobatue Radix + PNS group, Acori Tatarinowii Rhizoma + PNS group according to the random number table method, with 20 rats in each group. Except for the sham-operation group, the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups. After 7 d of administration of the appropriate pharmacologic intervention in each group, neurological dysfunction was evaluated by Zea-longa score after final administration, cerebral infarct volume was determined by TTC staining; blood brain barrier (BBB) permeability of brain tissue on the ischemic side was detected by Evans blue content; BBB ultrastructure of each group of rats was observed by transmission electron microscopy; Claudin 5 protein expression level was detected by immunohistochemistry; Zonula occludens-1 (ZO-1), major facilitator supeffamily domain-containing protein 2a (Mfsd2a), Occludin, P-glycoprotein (P-gp), Monocarboxylate Transporters-1 (MCT1) and breast cancer resistance protein (BCRP) protein expression levels were detected by Western-blot.Results:Compared with the model group, the rat neurological function scores were reduced in each administration group ( P<0.05), infarct volume was reduced ( P<0.05), EB content of brain tissue decreased ( P<0.05), protein expressions of Claudin 5, ZO-1, Mfsd2a and Occludin in brain tissue were elevated ( P<0.05), the protein expressions of P-gp, BCRP and MCT1 were reduced ( P<0.05), and the protein expressions of Claudin 5, Mfsd2a, and Occludin was higher in the Puerariae Lobatue Radix + PNS group and Acori Tatarinowii Rhizoma + PNS group than that of each group of medication alone ( P<0.05), and the protein expression of MCT1 was lower than that of each group of medication alone ( P<0.05); the protein expression level of ZO-1 in the Puerariae Lobatue Radix + PNS group was higher than that of the group of medication alone ( P<0.05); P-gp protein expression was lower in Acori Tatarinowii Rhizoma + PNS group than in the PNS group and Acori Tatarinowii Rhizoma group ( P<0.05). Conclusion:Wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) may potentiate the neuroprotective effect of PNS on cerebral ischemia-reperfusion rats, and the mechanism may be related to the protection of BBB structural integrity and maintenance of central barrier properties, while regulating substance transport proteins and increasing the intracerebral content of the drug.
8.Evaluation of quality of life instrument for nephrotic syndrome based on generalization theory and item response theory
Yue LIN ; Xingshan ZHANG ; Junhao GUO ; Wendan CHEN ; Chonghua WAN ; Haiyan PAN
Chongqing Medicine 2024;53(9):1295-1300
Objective To evaluate the performance of the Quality of Life Instrument for Chronic Dis-ease Nephrotic Syndrome [QLICD-NS(V2.0)] in patients with nephrotic syndrome.Methods A total of 203 patients with nephrotic syndrome (NS) diagnosed in the Department of Nephrology,Affiliated Hospital of Guangdong Medical University from March 2021 to November 2021 were selected for QLICD-NS(V2.0) eval-uation,and the evaluation methods were generalization theory (GT) and item response theory (IRT).The dif-ficulty,discrimination coefficient and information amount of each item were obtained by using Multilog 7.0 software to analyze the grade response model (GRM) of IRT.Results The results of GT showed that the contribution ratio of the global total score in the four domains of QLICD-NS(V2.0) scale was evenly distribu-ted,and the generalization coefficient of the four domains was greater than 0.50.Except for social function,the variance component of the participants in the other three domains were greater than the item variance compo-nent,and the reliability index of each domain was greater than 0.50.The results of IRT showed that the dis-crimination degree of QLICD-NS(V2.0) scale was 0.82.Except for items TNS7 and TNS8,the difficulty coef-ficients of the other items ranged from -3 to 3 and increase monotonically.Conclusion The QLICD-NS (V2.0) scale has good reliability in physiological function and psychological function,and is acceptable in so-cial field and special function.The QLICD-NS(V2.0) scale developed in this study has good performance.
9.Exploration on application value of 18F-PSMA-1007 PET/CT in diagnostic evaluation and treatment decision of prostate cancer
Jian CHEN ; Qiming CHEN ; Xiao CHEN ; Renxiang XIA ; Ze WANG ; Junhao JIN ; Xuzhi YAN ; Qiuli LIU ; Zehua SHU ; Yao ZHANG ; Jun ZHANG ; Luofu WANG ; Weihua LAN ; Jun JIANG
Chongqing Medicine 2024;53(22):3418-3428
Objective To investigate the value of 18F labeled prostate-specific membrane antigen(18F-PSMA)-1007 developing agent PET/CT(18F-PSMA-1007PET/CT)examination in the diagnostic evaluation and therapeutic decision of the newly diagnosed prostate cancer(PCa)and follow up after radical prostatecto-my(RP).Methods This study adopted the retrospective observational study method.A total of 68 patients receiving 18 F-PSMA-1007 PET/CT examination in this hospital from September 2022 to October 2023 were analyzed,including 36 cases of newly diagnosed PCa and 32 cases of biochemistry follow up failure after RP.A total of 30 items of clinical data were collected,including 8 items of basic clinical characteristics,7 items of pa-thology-related characteristics and 15 items of imaging characteristics.The patients clinical characteristics in the newly diagnosed PCa and biochemical failure after RP conducted the descriptive analysis.The Fisher exact probability method was used to analyze the differentiation of the SUVmax of primary lesions in different clini-cal subgroups[different tPSA levels at diagnosis,different mi-T stages,different Gleason scores at postopera-tive pathological puncture and different pathological types]in the newly diagnosed PCa group and the differ-entiation of recurrent lesion detection rates in different clinical subgroups(different tPSA in 18F-PSMA-1007 PET/CT examination,different pathological T stages,different lymph node invasion and different pathological Gleason scores in the biochemical failure after RP group.The Spearman correlation was adopted to test and analyze the correlation between the imaging features of positive lesions and tPSA.Results In the newly diag-nosed PCa group,there were 1 case of prostatic hyperplasia and 35 cases of PCa.SUVmax had no statistical differences among the primary lesions with different tPSA levels(P=0.81),different mi-T stages(P=0.70),different puncture Glleasonscores(P=0.20)and different pathological types(P=0.71).Moreover the tPSA value at diagnosis was positively correlated with the number of metastatic lesions(r=0.410,P=0.01).The clinical treatment decisions in 11 cases(31.43%)were changed according to the examination re-sults.In 9 cases of RP combined with lymph node dissection,the accuracy rate and concordance rate of 18F-PS-MA-1007 PET/CT and MRI in the lymph node detection rate all were 100%.I n the biochemical failure after RP group,the overall recurrent lesion detection rate was 71.88%(23/32),the operative area in situ recurrence(11 cases,34.38%)and bone metastasis(11 cases,34.38%)were most common.The differences of 18F-PS-MA-1007 PET/CT recurrent lesions detection rates had no statistical differences among the patients with dif-ferent tPSA levels(P=0.08),different pathological T stages(P=0.10),different postoperative pathological lymph node invasions(P=0.68)and different pathologic Gleason score in the 18F-PSMA-1007 PET/CT ex-amination.In the 18 F-PSMA-1007 PET/CT examination in the biochemical failure after RP,the tPSA value in the recurrent lesion was positively correlated with the number of recurrent lesions(r=0.48,P=0.01),SUVmax value in the recurrent lesion(r=0.46,P=0.01)and the SUVmean value(r=0.38,P=0.03).The clinical treatment decision in 18 cases(56.25%)was changed according to the examination results.Conclusion 18 F-PSMA-1007 PET/CT has good diagnostic value and efficiency for primary lesion and metastasis lesion of new-ly diagnosed PCa and recurrent foci of biochemical failure after RP.
10.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.


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