1.Analysis of the safety and efficacy of neoadjuvant immunotherapy combined with chemotherapy for radical resection of locally advanced gastric cancer: a two-center propensity-matched study
Chenbin LYU ; Jun LU ; Binbin XU ; Hongda PAN ; Qiuxian CHEN ; Jie CHEN ; Yuqin SUN ; Yongbin ZHANG ; Lisheng CAI ; Fenglin LIU
Chinese Journal of Surgery 2025;63(10):952-961
Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.
2.Analysis of the safety and efficacy of neoadjuvant immunotherapy combined with chemotherapy for radical resection of locally advanced gastric cancer: a two-center propensity-matched study
Chenbin LYU ; Jun LU ; Binbin XU ; Hongda PAN ; Qiuxian CHEN ; Jie CHEN ; Yuqin SUN ; Yongbin ZHANG ; Lisheng CAI ; Fenglin LIU
Chinese Journal of Surgery 2025;63(10):952-961
Objective:To investigate the impact of neoadjuvant immunotherapy combined with chemotherapy on the safety and efficacy of radical resection in patients with cT3-4NxM0 gastric cancer.Methods:A retrospective cohort study method was used. The clinicopathological data of 515 patients who underwent radical gastrectomy after neoadjuvant treatment at Second Department of Gastric Surgery,Fudan University Shanghai Cancer Center and Department of Gastric Surgery,Zhangzhou Hospital Affiliated to Fujian Medical University from January 2020 to June 2023 were collected. Among them,379 patients received neoadjuvant chemotherapy alone(chemotherapy group),and 136 patients received neoadjuvant immunotherapy combined with chemotherapy(immunotherapy group). There were 382 males and 133 females,with an age of (58.4±10.9)years(range:26 to 85 years). To reduce the influence of potential confounding factors,a 1∶1 propensity score matching method was adopted,and the clamp value was 0.02. The peri-operative safety,imaging and postoperative pathological tumor regression,and prognosis were compared by independent sample t-test, Mann-Whitney U test, χ 2 test or Fisher exact probability method between the two groups. The Kaplan-Meier method was used to draw survival curves, and the differences between groups were compared by Log-rank test. Results:After matching, there were 101 patients in each of the chemotherapy group and the immunotherapy group. The baseline data of the patients in the two groups were evenly distributed (all P>0.05). According to the RECIST 1.1 criteria, the complete response rate (11.9% (12/101) vs. 4.0% (4/101)), partial response rate(68.3%(69/101) vs. 53.4%(54/101)), stable disease rate (17.8%(18/101) vs. 39.6%(40/101)) and disease progression rate (2.0%(2/101) vs. 3.0%(3/101)) between the immunotherapy group and the chemotherapy group were no statistical defferences ( χ2=14.374, P=0.002), and objective response rate (80.2%(81/101) vs. 57.4%(58/101), χ2=12.203, P<0.01) in the immunotherapy group was higher than that in the chemotherapy group. The results of postoperative pathological examination showed that the immunotherapy group had a higher complete response rate (16.8%(17/101) vs. 6.9% (7/101), χ2=4.728, P=0.030) and major pathological response rate (42.6%(43/101) vs. 23.8% (24/101), χ2=8.062, P=0.005). For the two groups, the operation time (175.0(76.0)minutes vs. 160.0 (30.0)minutes, Z=-0.059, P=0.953), intraoperative blood loss (110.0 (150.0)ml vs. 100.0 (120.0)ml, Z=-0.370, P=0.712), overall incidence of postoperative complications (20.8%(21/101) vs. 18.8%(19/101), χ2=0.125, P=0.724) and incidence of severe complications (5.0%(5/101) vs. 3.0%(3/101), χ2=0.130, P=0.718) were comparable. The median follow-up time of all patients was 46 months(range: 19 to 61 months). The 3-year overall survival rate (63.2% vs. 54.4%, P=0.035) and progression-free survival rate (59.1% vs. 45.6%, P=0.022) of the immunotherapy group were higher than those of the chemotherapy group. Meanwhile, there were no statistically significant differences in the incidence of neoadjuvant-treatment-related adverse events (48.5%(49/101) vs. 40.6% (41/101), χ2=1.283, P=0.411) and the incidence of severe adverse reactions of grade 3 or above (13.9% (14/101) vs. 10.9% (11/101), χ2=0.257, P=0.522) between the two groups. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy can significantly improve the imaging and postoperative pathological tumor response rates and 3-year survival rate of patients with locally advanced gastric cancer,without increasing the incidence of postoperative complications and neoadjuvant treatment-related adverse event.
3.Diagnostic value of acid indigocarmine mixture sandwich staining combined with flexile spectral imaging color enhancement colonoscopy Pit pattern classification for colorectal lesions
Junping LU ; Yuxi LI ; Qiuxian LIU ; Shuming LI ; Aihua WU ; Zhaofu QU
China Journal of Endoscopy 2024;30(9):61-70
Objective To explore the diagnostic value of acetic acid indigocarmine mixture(AIM)sandwich staining combined with flexile spectral imaging color enhancement(FICE)technology for colonoscopic Pit pattern classification for colorectal lesions.Methods 100 patients with colorectal lesions from June 2022 to October 2023 were selected as the research subjects,and 222 lesions;Patients were examined using conventional endoscopy,FICE,AIM sandwich staining+FICE,and the detection status and pathological type of Pit pattern classification were recorded.Calculate the sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),and accuracy of Pit pattern classification diagnosis under different modes.Kappa was used to evaluate the consistency between Pit pattern classification and pathological examination under different modes.Evaluate diagnostic effectiveness using receiver operator characteristic curve(ROC curve).Results Compared with ordinary endoscopy(74.32%),FICE technology(92.34%)and AIM staining+FICE(97.30%)detected more lesions that matched the pathological results through Pit pattern classification,and AIM sandwich staining+FICE detected more than FICE,the differences were statistically significant(P<0.05).Compared with ordinary endoscopy,the diagnostic accuracy of FICE and AIM staining+FICE for colorectal carcinoma lesions were higher,and AIM sandwich staining+FICE higher than FICE,the differences were statistically significant(P<0.05).Compared with ordinary endoscopy,the diagnostic accuracy of FICE and AIM sandwich staining+FICE for early colorectal cancer were higher,the differences were statistically significant(P<0.05).The area under the curve(AUC)predicted by ordinary endoscopy,FICE and AIM sandwich staining+FICE for colorectal carcinoma lesions were 0.815(95%CI:0.711~0.859),0.881(95%CI:0.752~0.904),and 0.933(95%CI:0.793~0.961),respectively;The AUC predicted by ordinary endoscopy,FICE and AIM sandwich staining+FICE for early colorectal cancer were 0.850(95%CI:0.720~0.866),0.938(95%CI:0.764~0.951),and 0.947(95%CI:0.803~0.972),respectively.For predicting colorectal carcinoma lesions and early colorectal cancer,the Youden index of AIM staining+FICE technology was the highest,with values of 0.955 and 0.968,respectively.Conclusion Under AIM sandwich staining+FICE,Pit pattern classification can detect more carcinoma lesions and early colorectal cancer,with high diagnostic accuracy and effective improvement of endoscopic diagnosis and treatment quality.
4.Novel benzothiazole derivatives target the Gac/Rsm two-component system as antibacterial synergists against Pseudomonas aeruginosa infections.
Jun LIU ; Wenfu WU ; Jiayi HU ; Siyu ZHAO ; Yiqun CHANG ; Qiuxian CHEN ; Yujie LI ; Jie TANG ; Zhenmeng ZHANG ; Xiao WU ; Shumeng JIAO ; Haichuan XIAO ; Qiang ZHANG ; Jiarui DU ; Jianfu ZHAO ; Kaihe YE ; Meiyan HUANG ; Jun XU ; Haibo ZHOU ; Junxia ZHENG ; Pinghua SUN
Acta Pharmaceutica Sinica B 2024;14(11):4934-4961
The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC50 = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

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