1.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
2.Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study
Xinhua CHEN ; Hexin LIN ; Yuehong CHEN ; Xiaodong WANG ; Chaoqun LIU ; Huilin HUANG ; Huayuan LIANG ; Huimin ZHANG ; Fengping LI ; Hao LIU ; Yanfeng HU ; Guoxin LI ; Jun YOU ; Liying ZHAO ; Jiang YU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):694-701
Objective:To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer.Methods:The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results:Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ 2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026–0.828, P=0.030). Conclusion:Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.
3.Effect of ligustrazine on cardiac inflammation in rats with type 2 diabetes mellitus
Xinyuan ZHAO ; Kui XU ; Cairong LI ; Juan LI ; Fengping LIN ; Caiyan LI ; Jiazhong SUN ; Xiao CHEN
Chinese Journal of Pathophysiology 2017;33(4):744-748
AIM: To study the effect of ligustrazine on the cardiacmyocyte lesion in rats with type 2 diabetes mellitus.METHODS: Male Wistar rats were injected with STZ via tail vein under high-glucose and high-fat feeding for 4 weeks to establish the animal model of type 2 diabetes mellitus.Ligustrazine at different doses was used to treat the diabetic rats.The body weight, blood glucose and the morphology of heart tissues were observed.The myocardial levels of IL-1β, IL-6 and TNF-α were detected by ELISA, and the protein expression of IKKβ and NF-κB in the myocardium was determined by Westeren blotting.RESULTS: Ligustrazine at high dose alleviated the body weight reduction and blood glucose elevation cause by diabetes, and reduced pro-inflammatory factors IL-1β, TNF-α and IL-6.Moreover, the protein expression of IKKβ and NF-κB was significant decreased by ligustrazine.CONCLUSION: Ligustrazine inhibits the myocardial inflammation caused by diabetes through anti-inflammatory pathway.
4.Allergens detection and clinical analysis of prurigo nodularis in patients
Wei CAO ; Xiaoyuan WANG ; Xiaoyan ZHAI ; Xiaoying ZHU ; Ting XU ; Yingjuan WANG ; Fengping LIN ; Jianyu HE
Journal of Xi'an Jiaotong University(Medical Sciences) 2017;38(1):122-126
ABSTRACT:Objective To investigate the distributional characteristics of anaphylactogens in prurigo nodularis (PN)patients so as to provide clinical basis for selecting the method of allergy test.Methods We divided 262 PN patients into four groups and then used skin-prick (5 4 patients ),skin-patch (5 0 patients ),serum IgE allergen detection (56 patients)and serum IgG allergen detection (102 patients)to analyze anaphylactogen positive rate and their distribution differences in PN.Results For skin-prick test in 54 PN patients,the detection rates of platanus orientalis,artemisia argyi,poplar,dust mite,dirt mite,cod,peanut and tomato were higher than those in the control group (P<0.05 ).For skin-patch test in 50 PN patients,the detection rates of nickel sulfate,flavor compounds,black rubber,and carba mix were higher than those in the control group (P<0.05).For serum IgE test in 5 6 PN patients,the detection rates of house dust,scandent hop,cat/dog hair,bug,penicillium/neurospora and mutton were higher than those in the control group (P<0.05).For serum IgG test in 102 PN ones,the detection rates of crab,shrimp,beef and cod were higher than those in the control group (P<0.05).Conclusion Skin-prick test and serum IgE detection have high application values in PN patients.Serum IgG detection is of certain importance in adjusting PN patients’diet structure while skin-patch test applied in PN needs further exploration.
5.Clinical application of real-time fluorescence quantitative PCR for the detection of fecal tumor M2-pyruvate kinase in colorectal cancer patients
Yulan LIU ; Fengping HE ; Xin XU ; Qingsong WU ; Dingyun LI ; Zhanzhong MA ; Yanle GUO ; Sheng TANG ; Weidong YIN ; Haitao GONG ; Yi LIU ; Hengxian LIN
International Journal of Laboratory Medicine 2017;38(11):1444-1446
Objective To investigate the application valve of real-time fluorescence quantitative polymerase chain reaction(RT-PCR) for the detection of tumor M2-pyruvate kinase(tM2-PK) DNA in patients with colorectal cancer(CRC).Methods Fragment of tM2-PK DNA(162 bp) was amplified and inserted into PGM-T vector to construct recombinant plasmid,which was used to develop RT-PCR method.Sensitivity,specificity and repeatability of RT-PCR for the detection of tM2-PK were analyzed.From Jan.2014 to Jun.2016,200 CRC patients and 100 healthy subjects were enrolled and detected for fecal and serum tM2-PK DNA by using RT-PCR,and the detected results were compared with those detected by using enzyme linked immunosorbent assay(ELISA).Results Recombinant plasmid was successfully constructed,which was certified by sequencing.The sensitivity of RT-PCR for the detection of tM2-PK DNA was 10 copy/mL,with high specificity and 0.3%-2.9% of coefficient of variation.In patients,the positive rate of fecal tM2-PK DNA,detected by RT-PCR,was 92.50%,and that of ELISA to detect tM2-PK was 80.00%.Fecal and serum levels of tM2-PK were correlated with the pathologic stages of tumour.Conclusion Self-established RT-PCR could be specificity and sensitivity for the detection of fecal tM2-PK,which could be used for the early diagnosis of CRC.
6.Application of quantum dots immune fluorescent labelling in colorectal cancer tissues
Fengping HE ; Xin XU ; Qingsong WU ; Dingyun LI ; Zhanzhong MA ; Sheng TANG ; Weidong YIN ; Haitao GONG ; Hengxian LIN
International Journal of Laboratory Medicine 2016;37(18):2531-2533
Objective To investigate different antigens detected by a novel labelled reagent‐quantum dots(QDs) in the colorectal cancer tissues microarray(TMA) .Methods Depend on QDs streptavidin conjugate(QDs‐SA) combined specially with biotinylation IgG ,immune of luorescent histochemistry was utilized to examine expression of K‐ras ,matrix‐remodeling associated 5(MXRA5) proteins in the colorectal cancer TMA ,where the protein accurate location was observed .Results K‐ras ,matrix‐remodeling associ‐ated 5(MXRA5) proteins were high expressed in colorectal cancer tissue and located accurately in the cell membrane and nucleus of colorectal cancer cells ,respectively .Conclusion QDs exhibit excellent photostability ,broad emission spectrum and long fluorescence lifetime .Modified with streptavidin could accurately detect different protein locations in the colorectal cancer TMA .This is a novel approach for studying targeted imaging of colorectal cancer in vivo and vitro clinical diagnosis .
7.Influence of portal vein thrombosis on clinical efficacy of endoscopic esophageal variceal ligation
Lingjun CHEN ; Yunwei GUO ; Ying LIN ; Fengping ZHENG
Chinese Journal of Hepatic Surgery(Electronic Edition) 2016;5(3):153-157
ObjectiveTo explore the influence of portal vein thrombosis (PVT) on the clinical efifcacy of endoscopic esophageal variceal ligation (EVL) in cirrhotic patients with esophagogastric variceal hemorrhage (EVH).MethodsClinical data of 314 cirrhotic patients with EVH who underwent endoscopic EVL and were followed up for more than 6 months in the Third Afifliated Hospital of Sun Yat-sen University between January 2005 and December 2014 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. The patients were divided into the PVT group and the control group according to whether they had PVT during treatment. Among the 72 patients in the PVT group, 61 were males and 11 were females with the mean age of (50±11) years old.Among the 242 patients in the control group, 206 were males and 36 were females with the mean age of (47±11) years old. The clinical efifcacy of two groups was compared, and the correlation between PVT and the elimination rate of esophageal varices (EV) as well as the recurrent bleeding rate of EV was analyzed. The number of EVL treatment period in two groups was compared usingt test and the rate was compared using Chi-square test. Univariate logistic regression analysis was conducted for the correlation between PVT and the elimination rate, recurrent bleeding rate of EV.ResultsThirty-six patients in the PVT group and 115 patients in the control group developed acute EVH. After EVL, the emergency hemostatic rate of both groups was 100%. The elimination rate of EV in the PVT group was 76%(55/72), signiifcantly lower than 90%(218/242) in the control group (χ2=9.166,P<0.05). The number of EVL treatment period in the PVT group was 3.4±1.6, significantly more than 2.8±1.1 in the control group (t=3.065,P<0.05). The recurrent bleeding rate of EV in the PVT group was 36%(26/72), signiifcantly higher than 21%(51/242) in the control group (χ2=6.779,P<0.05). PVT was a risk factor for both the elimination rate of EV (OR=0.356, 95%CI: 0.179-0.709,P<0.05) and the recurrent bleeding rate of EV (OR=2.383, 95%CI: 1.354-4.196,P<0.05). ConclusionPVT is a risk factor for both the elimination rate of EV and the recurrent bleeding rate of EV in cirrhotic patients with EVH treated by endoscopic EVL.
8.Effect of SIRT1 on cell proliferation and senescence of human pancreaticβ-cells CRL-1837
Xiaoling TIAN ; Dongliang ZHU ; Fengping LIN ; Simin ZHU ; Guanya CHEN ; Caiyan LI
Chinese Journal of Endocrinology and Metabolism 2015;(7):621-622
Histone deacetylase 1 ( sirtuin 1, SIRT1) is an important member of deacetylase family, and plays an important role in the process of malignant tumor and embryonic development. In this article it was found that overexpression of SIRT1 could accelerate the DNA synthesis in human pancreatic beta cell CRL-1837 and inhibit cell senescence. SIRT1 also could bind to p53 as detected by co-immunoprecipitation and could change the phosphorylation level of p53.
9.Effect of miR-19a on lipid catabolism in hepatocyte LO2
Xiaoling TIAN ; Fengping LIN ; Weimin LI ; Xiufen LIU
Chinese Journal of Pathophysiology 2015;(3):481-484
[ ABSTRACT] AIM: To observe the effect of microRNA-19a ( miR-19a) on the lipid catabolism of hepatocyte LO2, and to explore the potential mechanism.METHODS: miR-19a was over-expressed or silenced by transfection of miR-19a mimics or miR-19a inhibitor into LO2 cells, then the mRNA level of miR-19a was detected by real-time PCR.The potential target of miR-19a was found by the method of bioinformatics through internet website.The effect of miR-19a on the 3’ UTR of peroxisome proliferator-activated receptorα(PPARα) was measured by dual luciferase reporter assay, and the protein level of PPARαand its 2 major downstream rate-limiting enzymes involved in lipid catabolism, acyl-coenzyme a dehydrogenase (ACADM) and carnitine palmitoyltransferase 1A ( CPT1A), were detected by Western blotting.Mean-while, the effect of miR-19a on the generation of ketone body was measured by beta-hydroxybutyric acid (β-OHB) detec-tion assay.RESULTS:The mRNA level of miR-19a was dramatically elevated by the transfection of miR-19a mimics, and sharply decreased by the transfection of miR-19a inhibitor (P<0.05).PPARαwas found as a potential target of miR-19a, and dual luciferase reporter assay and Western blotting confirmed the regulatory effect of miR-19a on the expression of PPARα, with the protein level changes of ACADM and CPT1A.miR-19a mimics down-regulated, while miR-19a inhibitor up-regulated the concentration ofβ-OHB in LO2 cells (P<0.05).CONCLUSION:miR-19a regulates the lipid catabo-lism of hepatocytes by targeting the PPARαand its 2 downstream rate-limiting enzymes.
10.Application value of ERCP in biliary stricture following liver transplantation
Zhie WU ; Huaying GU ; Yisui WANG ; Fengping ZHENG ; Yunwei GUO ; Ying LIN
Chinese Journal of Hepatic Surgery(Electronic Edition) 2015;(3):173-175
ObjectiveTo investigate the application value of endoscopic retrograde cholangiopancreatography (ERCP) in biliary stricture following liver transplantation (LT).MethodsClinical data of 47 patients with biliary stricture following LT treated with ERCP in the Third Affiliated Hospital of Sun Yat-sen University between January 2008 and January 2014 were retrospectively studied. The informed consents of all patients were obtained and the local ethical committee approval had been received. Among the 47 patients, 41 were males and 6 were females with the age ranging from 24 to 62 years old and the median of 51 years old. Anastomotic stricture was observed in 31 cases and non-anastomotic stricture in 16 cases. ERCP was performed on patients to localize biliary stricture and then papillotomy was performed under the support of guide wire. The stricture was dilated progressively by dilating catheter or columnar balloon through the guide wire. Endoscopic nasobiliary drainage or plastic stent placement was chosen according to the ERCP results. The evaluation of curative effect was graded by cure, improvement, inefifcacy and restenosis.ResultsAll the 47 patients underwent ERCP successfully with totally 112 times. Nasobiliary drainage was performed 79 person-times, stent placement 33 person-times. Among the 31 patients with anastomtic stricture, 28 were cured and 3 were improved. Among the 16 patients with non-anastomtic stricture, 5 were cured, 3 were improved, and 8 were ineffective. The total cured rate of all the patients was 70% (33/47) and the effective rate was 83% (39/47). The incidence of complications was 9% (4/47), including 2 cases of mild pancreatitis, 1 case of hyperamylasemia and 1 case of biliary tract infection.ConclusionERCP is safe, effective and integrated in diagnosis and treatment for biliary stricture following LT, which is the ifrst choice for non-surgery treatment.

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