1.Prognosis of patients with resectable pancreatic ductal adenocarcinoma treated by AG or AG combined with PD-1 inhibitor regimen and application value of CCF risk score
Junnan HUANG ; Yiyun HUANG ; Linwei XU ; Fang HAN ; Qianwei JIANG ; Yuhua ZHANG
Chinese Journal of Digestive Surgery 2025;24(5):609-616
Objective:To evaluate the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated by gemcitabine and nab-paclitaxel (AG) or AG combined with pro-grammed death-1 (PD-1) inhibitor regimen and application value of the Cleveland Clinic Foundation (CCF) risk score.Methods:The retrospective cohort study was conducted. The clinicopathological data of 151 PDAC patients who were treated by AG regimen or AG combined with PD-1 inhibitor regimen in Zhejiang Cancer Hospital from January 2013 to March 2024 were collected. There were 84 males and 67 females, aged (64±9)years. Observation indicators: (1) comparison of clinical characteristics among resectable PDAC patients with different CCF risk score; (2) analysis of influencing factors for overall survival time of resectable PDAC patients; (3) survival of resectable PDAC patients. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinical characteristics among resectable PDAC patients with different CCF risk score. Based on CCF risk score, 102 of 151 patients were classified as low risk and 49 cases were classified as intermediate-to-high risk. There were signi-ficant differences in sex, age, smoking status, alcohol consumption, hypertension, and diabetes between the two categories ( P<0.05). (2) Analysis of influencing factors for overall survival time of resectable PDAC patients. Results of multivariate analysis showed that the treatment regimen was an indepen-dent influencing factor for overall survival time of resectable PDAC patients ( hazard ratio=1.976, 95% confidence interval as 1.065?3.666, P<0.05). (3) Survival of resectable PDAC patients. The follow-up time of 151 patients was 21.8(18.7,24.2)months, and the median overall survival time was 23.3(19.0,32.4)months. The follow-up time was 22.1(18.9,30.7)months of patients treated by AG regimen and 11.2(8.1,23.3)months of patients treated by AG combined with PD-1 inhibitor regimen, respectively. The median overall survival time of the two types of patients was 24.4(17.2,31.7)months and 16.9(8.9,24.9)months. The 1-year overall survival rates were 79.1% and 60.0%, and the 2-year overall survival rates were 53.4% and 28.5%, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=1.913, 95% confidence interval as 1.041?3.516, P<0.05). Of the intermediate-to-high risk patients, the follow-up time was 18.5(8.8,28.1)months of 37 patients treated by AG regimen and 8.1(7.3,9.0)months of 12 patients treated by AG combined with PD-1 inhibitor regimen. The median overall survival time of the two types of patients was 32.4(15.7,49.0)months and 8.9(5.7,12.1)months, respectively. The 1-year overall survival rates were 82.7% and 31.3%, and the 2-year overall survival rates were 66.5% and 0, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=5.402, 95% confidence interval as 1.811?16.118, P<0.05). Conclusions:The treatment regimen is an independent influencing factor for overall survival in patients with resectable PDAC. Compared with the AG combined with PD-1 inhibitor regimen, AG regimen is associated with good survival of patients with resectable PDAC. For patients classified as intermediate-to-high risk based on the CCF risk score, AG regimen is assiociated with a better overall survival compared to AG combined with PD-1 inhibitor regimen.
2.Prognosis of patients with resectable pancreatic ductal adenocarcinoma treated by AG or AG combined with PD-1 inhibitor regimen and application value of CCF risk score
Junnan HUANG ; Yiyun HUANG ; Linwei XU ; Fang HAN ; Qianwei JIANG ; Yuhua ZHANG
Chinese Journal of Digestive Surgery 2025;24(5):609-616
Objective:To evaluate the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated by gemcitabine and nab-paclitaxel (AG) or AG combined with pro-grammed death-1 (PD-1) inhibitor regimen and application value of the Cleveland Clinic Foundation (CCF) risk score.Methods:The retrospective cohort study was conducted. The clinicopathological data of 151 PDAC patients who were treated by AG regimen or AG combined with PD-1 inhibitor regimen in Zhejiang Cancer Hospital from January 2013 to March 2024 were collected. There were 84 males and 67 females, aged (64±9)years. Observation indicators: (1) comparison of clinical characteristics among resectable PDAC patients with different CCF risk score; (2) analysis of influencing factors for overall survival time of resectable PDAC patients; (3) survival of resectable PDAC patients. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinical characteristics among resectable PDAC patients with different CCF risk score. Based on CCF risk score, 102 of 151 patients were classified as low risk and 49 cases were classified as intermediate-to-high risk. There were signi-ficant differences in sex, age, smoking status, alcohol consumption, hypertension, and diabetes between the two categories ( P<0.05). (2) Analysis of influencing factors for overall survival time of resectable PDAC patients. Results of multivariate analysis showed that the treatment regimen was an indepen-dent influencing factor for overall survival time of resectable PDAC patients ( hazard ratio=1.976, 95% confidence interval as 1.065?3.666, P<0.05). (3) Survival of resectable PDAC patients. The follow-up time of 151 patients was 21.8(18.7,24.2)months, and the median overall survival time was 23.3(19.0,32.4)months. The follow-up time was 22.1(18.9,30.7)months of patients treated by AG regimen and 11.2(8.1,23.3)months of patients treated by AG combined with PD-1 inhibitor regimen, respectively. The median overall survival time of the two types of patients was 24.4(17.2,31.7)months and 16.9(8.9,24.9)months. The 1-year overall survival rates were 79.1% and 60.0%, and the 2-year overall survival rates were 53.4% and 28.5%, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=1.913, 95% confidence interval as 1.041?3.516, P<0.05). Of the intermediate-to-high risk patients, the follow-up time was 18.5(8.8,28.1)months of 37 patients treated by AG regimen and 8.1(7.3,9.0)months of 12 patients treated by AG combined with PD-1 inhibitor regimen. The median overall survival time of the two types of patients was 32.4(15.7,49.0)months and 8.9(5.7,12.1)months, respectively. The 1-year overall survival rates were 82.7% and 31.3%, and the 2-year overall survival rates were 66.5% and 0, respectively. There was a significant difference in the overall survival between the two types of patients ( hazard ratio=5.402, 95% confidence interval as 1.811?16.118, P<0.05). Conclusions:The treatment regimen is an independent influencing factor for overall survival in patients with resectable PDAC. Compared with the AG combined with PD-1 inhibitor regimen, AG regimen is associated with good survival of patients with resectable PDAC. For patients classified as intermediate-to-high risk based on the CCF risk score, AG regimen is assiociated with a better overall survival compared to AG combined with PD-1 inhibitor regimen.
3.Predictive value of Naples prognostic score on long-term outcome in patients with intrahepatic cholangiocarcinoma
Hang JIANG ; Xing CHEN ; Jia WU ; Fang HAN ; Chao HU ; Linwei XU ; Jiangshu LIU ; Yuhua ZHANG
Chinese Journal of General Surgery 2024;39(8):609-614
Objective:To investigate the predictive value of Naples prognostic score (NPS) in assessing the overall survival of intrahepatic cholangiocarcinoma (ICC) patients after receiving hepatectomy treatment.Methods:Clinicopathological characteristics and follow-up data of 164 ICC patients who underwent curative hepatectomy at Zhejiang Cancer Hospital from Jan 2010 to Aug 2022 were retrospectively collected. NPS was calculated basing on preoperative serum albumin concentration, total cholesterol concentration, the neutrophil-lymphocyte ratio, and lymphocyte-monocyte ratio. The relationship between NPS and overall survival was analyzed, and the efficacy of NPS in predicting long-term survival was compared to TNM staging system and other independent risk factors.Results:Multivariate analysis identified the NPS [Score 1 versus 0: 1.864 (1.011-3.437), P=0.046; Score 2 versus 0: 3.013 (1.465-6.199), P=0.003] as an independent risk factor for overall survival. The area under curve (AUC) of the rece中iver operating characteristic (ROC) curve for predicting 5-year OS based on NPS is 0.75, which is higher than TNM staging (0.59) and other independent risk factors (CA19-9:0.71, lymph node metastasis: 0.66, tumor size: 0.62, microvascular invasion: 0.56). Conclusion:NPS as an independent predictor of overall survival for ICC patients, is more accurate than TNM staging system and other clinicopathological factors.
4.All-stage targeted therapy for the brain metastasis from triple-negative breast cancer.
Zimiao LUO ; Sunyi WU ; Jianfen ZHOU ; Weixia XU ; Qianzhu XU ; Linwei LU ; Cao XIE ; Yu LIU ; Weiyue LU
Acta Pharmaceutica Sinica B 2023;13(1):359-371
Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.
5.Production and application of rabbit polyclonal antibody against mouse testis expressed 38 (TEX38).
Ling YANG ; Lu YUAN ; Fan YANG ; Tingting GE ; Wenhua XU ; Linwei XU ; Changmin NIU ; Ying ZHENG
Chinese Journal of Cellular and Molecular Immunology 2023;39(10):933-939
Objective To produce rabbit polyclonal antibody against mouse testis expressed 38 (TEX38). Methods Full-length open reading frame sequence of TEX38 was amplified and inserted into the pET-30a-(+) vector to construct pET-30a-TEX38 prokaryotic plasmid. The recombinant plasmid was transformed into E.coli BL21, and expression was induced with isopropyl β-D-thiogalactopyranoside (IPTG). New Zealand white rabbits were immunized with TEX38 protein after purification and denaturation, then TEX38 polyclonal antibodies were collected from rabbit serum samples. ELISA was performed to detect the antibody titer. Western blot and immunofluorescence staining were performed to determine the specificity of TEX38 polyclonal antibodies. Results The pET-30a-TEX38 recombinant plasmid was constructed, and TEX38 prokaryotic protein was expressed and purified successfully. After immunization, the titer of TEX38 antibody reached 1:1 000 000. Western blot analysis and immunofluorescence staining showed that TEX38 was localized in the mouse spermatogenic cells and sperms with a good specificity. Conclusion The rabbit polyclonal antibody against mouse TEX38 is successfully produced, and the expression of TEX38 in mouse spermatogenic cells and sperms is validated.
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6.Preoperative simulative resection in laparoscopic anatomical hepatectomy
Jia WU ; Fang HAN ; Yuhua ZHANG ; Linwei XU ; Yizhen CHEN ; Youyao XU ; Yurun HUANG ; Hang JIANG
Chinese Journal of General Surgery 2022;37(11):812-816
Objective:To formulate surgical strategies and guide the implementation of laparoscopic anatomical hepatectomy with preoperative simulative resection.Methods:Twenty-two cases of hepatocellular carcinoma undergoing laparoscopic lobe, segment, subsegment and combined segment liver resection following preoperative simulative resection from Sep 2020 to Jan 2022 were enrolled in this study retrospectively.We observed and analyzed the operation time,intraoperative blood loss,postoperative hospital stay and postoperative complication.Results:All patients underwent laparoscopic hepatectomy successfully according to the preoperative simulative resection plan without conversion, some of them adjusted plan according to preoperative simulative resection. The median operation time was 170.0 min, the median intraoperative blood loss was 150.0 ml, the median times of pringle maneuver was done on 4 episodes, and the median postoperative hospital stay was 6.5 days. There were no severe postoperative complications in all cases.Conclusion:Preoperative simulative resection can plan the range of surgical resection accurately by visualizing important anatomical structures,greatly helping the actual surgical hepatectomy.
7.Effect of psoas major intramuscular block therapy on the early complications related to the multi-segmental crenel lumbar interbody fusion
Zexiang ZHONG ; Fangcai LI ; Qixin CHEN ; Weishan CHEN ; Zhiwei WANG ; Linwei CHEN ; Guoping XU ; Yuanqing SHEN
Chinese Journal of Orthopaedics 2021;41(13):825-833
Objective:To explore the clinical effect of the application of intraoperative psoas major intramuscular block therapy on the complications related to the approach after multi-segmental crenel lumbar interbody fusion (CLIF).Methods:All of 68 degenerative lumbar scoliosis patients who had received multi-segmental crenel lumbar interbody fusion during January 2020 and June 2020 were retrospectively reviewed. Patients were divided into two groups according to whether the psoas major muscle was treated with block therapy during the operation. The psoas muscle inblock group were filled with gel sponge infiltrated with a mixture of Betamethasone and lidocaine for local block therapy before closing the incision while that in the control group were not filled with gel sponge. There were 33 patients in the control group, 7 males and 26 females with an average of 65.8±7.1 years old (range: 54-81 years old); 35 cases in the block group, 9 males and 26 females with an average of 68.0±6.5 years old (range: 54-85 years old). The complications related to the approach (mainly includes pain, numbness in the front of the thigh, as well as psoas major, quadriceps muscle strength) were recorded respectively 1 day, 1 week, 1 month and 3 months after surgery. The main indicators of outcome including visual analog scale (VAS) of pain, the visual analog scale (VAS) of numbness, muscle strength of psoas major and quadriceps femoris, and the incidence of complications related to the approach were compared between the two groups of patients at different time points after surgery. The clinical outcomes were assessed using the Oswestry disability index (ODI), VAS for low back pain. The radiological outcome was evaluated with Cobb angles and sagittal balance parameters (sagittal vertical axis, SVA).Results:There were no significant differences in age, gender, body mass index (BMI), number of fusion segments, operation time, and intraoperative blood loss between the two groups. The incidence of approach-related complications was 17.1% in the block group and 39.4% in the control group, with statistically significant difference between the two groups ( χ2=4.177, P=0.041). The incidence of postoperative pain, numbness in the front of the thighs, and muscle strength of psoas major in the block group (11.4%, 14.3%) were lower than those in the control group (33.3%, 36.4%) ( χ2=4.740, P=0.029; χ2=4.416, P=0.036). And for numbness in the front of thigh, the block group (14.3) was lower than control group (21.2%), but no significant difference was shown between two groups ( χ2=0.561, P=0.454). However, there was no quadriceps weakness in either group. The VAS scores of painof the block group were lower than those of the control group at 1 day, 1 week, and 1 month after surgery, and the difference was statistically significant ( t=2.220, P=0.031; t=2.235, P=0.031; t=2.086, P=0.044). The difference at 3 months was not statistically significant ( t=0.385, P=0.701). The muscle strength of psoas major of the block group, meanwhile, was higher than those of the control group on the 1day and 1 week after surgery, the difference was statistically significant as well ( t=2.208, P=0.032; t=2.171, P=0.034). The difference at 1 and 3 months was not statistically significant ( t=0.923, P=0.359; t=1.437, P=0.160). No statistically significant differences were found in VAS scores of numbness at 1 day, 1 week, 1 month, and 3 months after surgery. Postoperative low back pain and lumbar spine function were significantly improved in both groups, and there was no statistical significance between the two groups. Coronal Cobb angle and sagittal balance were significantly improved in both groups after surgery, and there was no statistical significance between the two groups. Conclusion:Psoas major intramuscular block therapy can reduce the incidence of early postoperative complications of multi-segmental CLIF. Furthermore, it was found to be effective to alleviate anterior thigh pain within 1 month, and improve psoas major muscle weakness within 1 week.
8. Effect of Bigelovii A on hepatocellular carcinoma by regulating SHP and STAT signaling pathway
Fuqin GUAN ; Yu SHAN ; Yu CHEN ; Qizhi WANG ; Linwei LI ; Xu FENG ; Haiying TONG ; Xu FENG
Chinese Pharmacological Bulletin 2021;37(2):192-195
Aim To investigate the effect of Bigelovii A on HepG2 cell apoptosis and its possible mechanism. Methods MTT assay was used to determine the inhibitory effect of Bigelovii A on HepG2 cells. Flow cytometry was performed to detect apoptosis. Western blot was applied to detect the expression of proteins of STAT pathway. Results BA (20 μmol L
9.Effect of tripterygium on growth,invasion and angiogenesis of A375 melanoma and its action mechanisms
Hongtao XU ; Zhongbao HAN ; Huili ZHANG ; Linwei MA
Chongqing Medicine 2016;45(20):2752-2755
Objective To investigate the effect of tripterygium on the grow th ,invasion and angiogenesis of melanoma A375 and its action mechanisms .Methods MTS was used to test the effect of tripterygium on proliferation of A375 melanoma;the nude mouse subcutaneous melanoma xenograft model was used to detect the effect of tripterygium on tumor growth ;the Transwell ex‐periment was used to determine the effect of tripterygium on invasion of A 375 melanoma;the tubule formation experiment was used to determine the effect of tripterygium on tumor angiogenesis ;ELISA was used to detect the influence of tripterygium on A 375 cel‐lular secretion factors ,such as VEGF ,bFGF ,TGF‐βand IL‐8 .Results The in vitro proliferation and in vivo growth of A375 mela‐noma cells after tripterygium treatment were significant inhibited ,the invasion ability of A375 melanoma cells was significant weak‐ened compared with the control group ;tripterygium could inhibit tumor cell‐induced vessel formation by down‐regulating the ex‐pression of VEGF ,bFGF and IL‐8 proteins ,but it had no influence on expression of TGF‐βprotein .Conclusion Tripterygium has anti‐growth and anti‐invasion effects on A375 melanoma ,its potential mechanisms may associated with the inhibition of tumor an‐giogenesis of A375 melanoma .
10.Inhibitory effect of paeoniflorin on inflammatory chemokines and their receptor in a mouse model of asthma
Jiaqi LIU ; Zhengxiao ZHAO ; Ying WEI ; Fei XU ; Hongying ZHANG ; Mihui LI ; Linwei LU ; Kai WEI ; Jingcheng DONG
Acta Laboratorium Animalis Scientia Sinica 2016;24(5):460-464
Objective To study the effect of paeoniflorin on inflammatory chemokines and their receptor in a rat model of ovalbumin-induced asthma.Methods Sixty 6-week old SPF female BALB/c mice were used in this study.To es-tablish a mouse model of asthma by sensitizing and challenging with ovalbumin.ELISA was used to analyze the serum IL-6 and TNF-α, and the specific IgE against ovalbumin ( OVA-IgE ) , CCL19 and CCL21 in bronchoalveolar lavage fluid (BALF).RT-PCR was performed to determine CCR7mRNA and protein expression of chemokine receptor CCR7, and the level of NF-κB was tested by Western blot.ResultsIn In the paeoniflorin groups, the serum IL-6 and TNF-αlevels were significantly lower, and the OVA-IgE, CCL19 and CCL21 levels in BALF were significantly reduced, compared with that in the control group.CCR7mRNA and protein expression of chemokine receptor CCR7 and NF-κB in the lung were significant-ly reduced by paeoniflorin.Conclusions Paeoniflorin has a remarkably inhibitory effect on the airway inflammatory chemo-kines CCL19/CCL21 and the receptor CCR7 in the mouse model of asthma.

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