1.Effect of composite electromagnetic stimulation combined with chin tuck against resistance on post-stroke pa-tients with dysphagia
Guojun FU ; Xiufang YU ; Xin LÜ ; Lu JI ; Huaqing LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(6):721-728
Objective To explore the effect of composite electromagnetic stimulation combined with chin tuck against resistance(CTAR)on post-stroke dysphagia.Methods From January,2021 to December,2023,156 post-stroke patients with pharyngeal dysphagia in the First Peo-ple's Hospital of Yibin were randomly divided into CTAR group(n=51),neuromuscular electrical stimulation(NMES)+repetitive transcranial magnetic stimulation(rTMS)group(n=52)and combination group(n=53).On the basis of routine swallowing function training,they received CTAR,NMES+rTMS and NMES+rTMS+CTAR,respectively,for four weeks.They were assessed with Functional Oral Intake Scale(FOIS),Standardized Swal-lowing Assessment(SSA),Swallowing-Quality of Life(SWAL-QOL),Rosenbek Penetration Aspiration Scale(PAS),video fluoroscopic swallowing study(VFSS)(including the score of VFSS,pharyngeal transit time,and upward and forward displacement of hyoid bone),average surface electromyography(AMEG)of submental and hyoid muscles,before and after treatment.Results The inter-group effect,intra-group effect and interaction effect were significant in SSA,SWAL-QOL and AMEG of the two muscles(F>6.611,P<0.001).The inter-group effect and interaction effect were significant in FOIS,VFSS,pharyngeal transit time,upward displacement of hyoid bone and forward displacement of hyoid bone(F>3.451,P<0.05).Pairwise comparison results showed that pharyngeal transit time was shorter in the combination group than in NMES+rTMS group(P=0.048),forward displacement of hyoid bone was more in the combina-tion group than in CTAR group(P=0.002),and AMEG was higher in the combination group than in CTAR group and NMES+rTMS group(P<0.001).There was significant difference in the score of PAS among three groups(Hc=8.282,P=0.016),and it was the best in the combination group.Conclusion The combination of NMES+rTMS and CTAR is superior to single electromagnetic stimulation or CTAR in the treatment of post-stroke sysphagia.
2.Effects of nutritional therapy based on indirect calorimetry in patients with extremely severe burns during hypermetabolic stage
Bin JIANG ; Yong DU ; Yilan XIA ; Huaqing CHEN ; Fuchang LU
Chinese Journal of Burns 2025;41(1):94-100
Objective:To explore the effects of nutritional therapy based on indirect calorimetry in patients with extremely severe burns during hypermetabolic stage.Methods:This study was a retrospective cohort study. From March 25, 2022 to March 30, 2024, 20 extremely severe burn patients who met the inclusion criteria were admitted to the Department of Burn and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 15 males and 5 females, aged (46±12) years. The patients were divided into death group (6 cases) and survival group (14 cases) according to their treatment outcomes. At the 3 rd, 7 th, 14 th, and 21 st d after injury, the resting energy expenditure (REE) of patients in the two groups was measured by indirect calorimetry once a day, and the nutritional treatment scheme was formulated according to the results of REE. The REE value, levels of albumin and interleukin-6 (IL-6), actual energy intake, and enteral nutrition energy intake of patients in the two groups at the 3 rd, 7 th, 14 th, and 21 st d after injury were collected (the last two indicators were respectively expressed as the mean values of the 3 rd to 6 th, 7 th to 10 th, 14 th to 17 th, and 21 st to 24 th d after injury). The actual energy intake/REE value and enteral nutrition energy intake/actual energy intake were calculated. Results:The REE values of patients in survival group and death group were (8 143±2 328), (9 843±2 610), (10 149±2 248), (9 608±2 838) kJ and (6 816±2 057), (10 691±2 515), (11 031±2 850), (8 990±2 018) kJ, respectively at the 3 rd , 7 th, 14 th, and 21 st d after injury. The REE value and enteral nutrition energy intake of patients in the two groups showed trends of increase first and decrease then from the 3 rd to 21 st d after injury, while the differences in the above two indicators at each time point between the two groups of patients were not statistically significant ( P>0.05). The actual energy intake of patients in survival group at the 21 st d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05), and the enteral nutrition energy intake of patients in death group at the 14 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). There were no statistically significant differences in overall comparison in actual energy intake/REE value and enteral nutrition energy intake/actual energy intake at each time point after injury between and within the two groups of patients ( P>0.05). The level of IL-6 of patients in survival group at the 21 st d after injury was significantly lower than that at the 3 rd and 7 th d after injury, respectively (with both P values <0.05), and significantly higher than that at the 14 th d after injury ( P<0.05); the level of IL-6 of patients in death group at the 21 st d after injury was significantly higher than that at the 3 rd, 7 th, and 14 th d after injury (with P values all <0.05). The albumin level of patients in survival group at the 7 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). Conclusions:The REE value and enteral nutrition energy intake of extremely severe burn patients showed trends of increase first and decrease then, while they have no significant effects on the clinical outcome of the patients. The nutritional treatment scheme based on the indirect calorimetry can basically meet the energy demand of patients with extremely severe burns during hypermetabolic stage. The impacts of the albumin and IL-6 levels on the clinical outcome of extremely severe burn patients still need further research.
3.Effect of composite electromagnetic stimulation combined with chin tuck against resistance on post-stroke pa-tients with dysphagia
Guojun FU ; Xiufang YU ; Xin LÜ ; Lu JI ; Huaqing LIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(6):721-728
Objective To explore the effect of composite electromagnetic stimulation combined with chin tuck against resistance(CTAR)on post-stroke dysphagia.Methods From January,2021 to December,2023,156 post-stroke patients with pharyngeal dysphagia in the First Peo-ple's Hospital of Yibin were randomly divided into CTAR group(n=51),neuromuscular electrical stimulation(NMES)+repetitive transcranial magnetic stimulation(rTMS)group(n=52)and combination group(n=53).On the basis of routine swallowing function training,they received CTAR,NMES+rTMS and NMES+rTMS+CTAR,respectively,for four weeks.They were assessed with Functional Oral Intake Scale(FOIS),Standardized Swal-lowing Assessment(SSA),Swallowing-Quality of Life(SWAL-QOL),Rosenbek Penetration Aspiration Scale(PAS),video fluoroscopic swallowing study(VFSS)(including the score of VFSS,pharyngeal transit time,and upward and forward displacement of hyoid bone),average surface electromyography(AMEG)of submental and hyoid muscles,before and after treatment.Results The inter-group effect,intra-group effect and interaction effect were significant in SSA,SWAL-QOL and AMEG of the two muscles(F>6.611,P<0.001).The inter-group effect and interaction effect were significant in FOIS,VFSS,pharyngeal transit time,upward displacement of hyoid bone and forward displacement of hyoid bone(F>3.451,P<0.05).Pairwise comparison results showed that pharyngeal transit time was shorter in the combination group than in NMES+rTMS group(P=0.048),forward displacement of hyoid bone was more in the combina-tion group than in CTAR group(P=0.002),and AMEG was higher in the combination group than in CTAR group and NMES+rTMS group(P<0.001).There was significant difference in the score of PAS among three groups(Hc=8.282,P=0.016),and it was the best in the combination group.Conclusion The combination of NMES+rTMS and CTAR is superior to single electromagnetic stimulation or CTAR in the treatment of post-stroke sysphagia.
4.Lymph node dissection extent in stage Ⅲ right-sided colon cancer: a single-center, retrospective cohort study
Kexuan LI ; Huaqing ZHANG ; Bin WU ; Guole LIN ; Junyang LU ; Xiyu SUN ; Beizhan NIU ; Lai XU ; Guannan ZHANG ; Zheng SUN ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1026-1033
Objective:To compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.
5.Lymph node dissection extent in stage Ⅲ right-sided colon cancer: a single-center, retrospective cohort study
Kexuan LI ; Huaqing ZHANG ; Bin WU ; Guole LIN ; Junyang LU ; Xiyu SUN ; Beizhan NIU ; Lai XU ; Guannan ZHANG ; Zheng SUN ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2025;28(9):1026-1033
Objective:To compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.
6.Effects of nutritional therapy based on indirect calorimetry in patients with extremely severe burns during hypermetabolic stage
Bin JIANG ; Yong DU ; Yilan XIA ; Huaqing CHEN ; Fuchang LU
Chinese Journal of Burns 2025;41(1):94-100
Objective:To explore the effects of nutritional therapy based on indirect calorimetry in patients with extremely severe burns during hypermetabolic stage.Methods:This study was a retrospective cohort study. From March 25, 2022 to March 30, 2024, 20 extremely severe burn patients who met the inclusion criteria were admitted to the Department of Burn and Wound Repair of the Second Affiliated Hospital of Zhejiang University School of Medicine. There were 15 males and 5 females, aged (46±12) years. The patients were divided into death group (6 cases) and survival group (14 cases) according to their treatment outcomes. At the 3 rd, 7 th, 14 th, and 21 st d after injury, the resting energy expenditure (REE) of patients in the two groups was measured by indirect calorimetry once a day, and the nutritional treatment scheme was formulated according to the results of REE. The REE value, levels of albumin and interleukin-6 (IL-6), actual energy intake, and enteral nutrition energy intake of patients in the two groups at the 3 rd, 7 th, 14 th, and 21 st d after injury were collected (the last two indicators were respectively expressed as the mean values of the 3 rd to 6 th, 7 th to 10 th, 14 th to 17 th, and 21 st to 24 th d after injury). The actual energy intake/REE value and enteral nutrition energy intake/actual energy intake were calculated. Results:The REE values of patients in survival group and death group were (8 143±2 328), (9 843±2 610), (10 149±2 248), (9 608±2 838) kJ and (6 816±2 057), (10 691±2 515), (11 031±2 850), (8 990±2 018) kJ, respectively at the 3 rd , 7 th, 14 th, and 21 st d after injury. The REE value and enteral nutrition energy intake of patients in the two groups showed trends of increase first and decrease then from the 3 rd to 21 st d after injury, while the differences in the above two indicators at each time point between the two groups of patients were not statistically significant ( P>0.05). The actual energy intake of patients in survival group at the 21 st d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05), and the enteral nutrition energy intake of patients in death group at the 14 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). There were no statistically significant differences in overall comparison in actual energy intake/REE value and enteral nutrition energy intake/actual energy intake at each time point after injury between and within the two groups of patients ( P>0.05). The level of IL-6 of patients in survival group at the 21 st d after injury was significantly lower than that at the 3 rd and 7 th d after injury, respectively (with both P values <0.05), and significantly higher than that at the 14 th d after injury ( P<0.05); the level of IL-6 of patients in death group at the 21 st d after injury was significantly higher than that at the 3 rd, 7 th, and 14 th d after injury (with P values all <0.05). The albumin level of patients in survival group at the 7 th d after injury was significantly higher than that at the 3 rd d after injury ( P<0.05). Conclusions:The REE value and enteral nutrition energy intake of extremely severe burn patients showed trends of increase first and decrease then, while they have no significant effects on the clinical outcome of the patients. The nutritional treatment scheme based on the indirect calorimetry can basically meet the energy demand of patients with extremely severe burns during hypermetabolic stage. The impacts of the albumin and IL-6 levels on the clinical outcome of extremely severe burn patients still need further research.
7.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.
8.Impacts of participation in surgical clinical trial on safety and survival outcomes in patients with right-sided colon cancer
Huaqing ZHANG ; Guoqiang WANG ; Bin WU ; Guole LIN ; Huizhong QIU ; Beizhan NIU ; Junyang LU ; Lai XU ; Xiyu SUN ; Guannan ZHANG ; Yi XIAO
Chinese Journal of Gastrointestinal Surgery 2024;27(9):928-937
Objective:To explore the impact on safety and prognosis in patients with right-sided colon cancer participating in surgical clinical research.Methods:This retrospective cohort study utilized data from a randomized controlled trial (RELARC study) conducted by the colorectal surgery group at Peking Union Medical College Hospital in which laparoscopic complete mesocolic excision (CME) was compared with D2 radical resection for the management of right-sided colon cancer. The eligibility criteria were age 18–75 years, biopsy-proven colon adenocarcinoma, tumor located between the cecum and right 1/3 of the transverse colon, enhanced chest, abdomen, and pelvic CT scans suggesting tumor stage T2–T4N0M0 or TanyN+ M0, and having undergone radical surgical treatment from January 2016 to December 2019. Exclusion factors included multiple primary colorectal cancers, preoperative stage T1N0 or enlarged central lymph nodes, tumor involving surrounding organs requiring their resection, definite distant metastasis or otherwise unable to undergo R0 resection, history of any other malignant tumors within previous 5 years, intestinal obstruction, perforation, or gastrointestinal bleeding requiring emergency surgery, and assessed as unsuitable for laparoscopic surgery. Patients who had participated in the RELARC study were included in the RELARC group, whereas those who met the inclusion criteria but refused to participate in the RELAEC study were included in the control group. The main indicators studied were the patient's baseline data, surgery and perioperative conditions, pathological characteristics, adjuvant treatment, and postoperative follow-up (including average frequency of follow-up within the first 3 years) and survival (including 3-year disease-free survival rate (DFS) and 3-year overall survival rate (OS). Differences in these indicators between the RELARC and control groups were compared.Results:The study cohort comprised 290 patients, 173 in the RELARC group (RELARC-CME group, 82; RELARC-D2 group, 91) and 117 in the control group (CME control group, 72; D2 control group, 45). There was a significantly higher proportion of overweight patients (BMI ≥24 kg/m 2) in the RELARC-CME than in the CME control group (67.1% [55/82] vs. 33.3% [24/72], χ 2=17.469, P<0.001). There were no other statistically significant differences in baseline characteristics (all P>0.05). No significant disparities were found between the CME and D2 groups in terms of operation duration, intraoperative blood loss, rate of conversion to open surgery, combined organ resection, intraoperative blood transfusion, or intraoperative complications (all P>0.05). There was a trend toward Clavien–Dindo grade II or higher postoperative complications in the RELARC-CME group (24.4% [20/82]) than in the CME control group (18.1% [13/72]); however, this difference was not statistically significant (χ 2=0.914, P=0.339). Similarly, the difference in this rate did not differ significantly between the RELARC-D2 group (25.3% [23/91]) and D2 control group (24.4% [11/45], χ 2=0.011, P=0.916). The median duration of postoperative follow-up was significantly shorter in the RELARC groups than in the corresponding control groups. Specifically, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-CME and 7.2 (6.0, 9.0) months in the CME control group ( Z=-10.608, P<0.001). Similarly, the median duration of follow-up was 4.5 (4.5, 4.5) months in the RELARC-D2 group as opposed to 8.3 (6.6, 9.0) months in the D2 control group ( Z=-10.595, P<0.001). The 3-year DFS rate (91.5%) and OS rate (96.3%) tended to be higher in the RELARC-CME group than in the CME control group (84.7% and 90.3%, respectively). The 3-year DFS rate (87.9%) and OS rate (96.7%) tended to be higher in the RELARC-D2 group than in the D2 control group (81.8% and 88.6%, respectively); however, these differences were not statistically significant (all P>0.05). Subgroup analysis according to pathological stage revealed that patients in the RELARC-D2 group with pN0 stage achieved a significantly superior 3-year OS rate than did those in the D2 control group (100% vs. 88.9%, P=0.008). We identified no statistically significant differences in survival rates between the remaining subgroups (all P>0.05). Conclusions:A high-quality surgical clinical trial with close follow-up can achieve perioperative safety and a trend toward improved survival outcomes.
9.Iron-based and BRD4-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-II-boosted nano-matchbox.
Lujing GENG ; Tong LU ; Huaqing JING ; Yue ZHOU ; Xiaoyang LIANG ; Jiao LI ; Nan LI
Acta Pharmaceutica Sinica B 2023;13(2):863-878
Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.
10.The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia.
Jian LU ; Xuyang SHANG ; Bingyi YAO ; Dongyi SUN ; Jie LIU ; Yuanjin ZHANG ; He WANG ; Jingru SHI ; Huaqing CHEN ; Tieliu SHI ; Mingyao LIU ; Xin WANG
Acta Pharmaceutica Sinica B 2023;13(2):648-661
Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.

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