1.Sulodexide alleviates renal fibrosis following prolonged ischemia-reperfusion injury by protecting vascular endothelial glycocalyx
Chaoyu HU ; Peng ZHANG ; Chao SUN ; Shuyong MO ; Yanfeng WANG
Organ Transplantation 2025;16(3):404-415
Objective To investigate the protective effects and mechanisms of sulodexide on renal fibrosis induced by prolonged warm ischemia. Methods An in vivo ischemia-reperfusion injury (IRI) model was established in rats, which were randomly divided into Sham group, IRI 60 min group (IRI group), and IRI 60 min + sulodexide group (IRI+SDX group), with 20 rats in each group. Pathological examination was used to evaluate renal tissue injury and fibrosis levels in each group. Immunohistochemistry was performed to detect the expression levels of kidney injury molecule (KIM)-1, intercellular adhesion molecule (ICAM)-1, von Willebrand factor (vWF), transforming growth factor (TGF)-β, α-smooth muscle actin (SMA), and type I collagen (COL-1). Immunofluorescence staining was used to detect CD31 expression. Real-time quantitative polymerase chain reaction was employed to measure the expression of KIM-1, ICAM-1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in renal tissues. Transmission electron microscopy was used to observe the structure of the renal glycocalyx. Evans blue dye was injected to assess renal vascular permeability. Rat survival was recorded, and serum levels of syndecan (SDC)-1, heparan sulfate (HS) and serum creatinine were measured. An ex vivo perfusion model was also established, with rats randomly assigned to either the hypothermic oxygenated machine perfusion (HOPE) group or the HOPE+SDX group (five rats per group). Perfusion parameters were recorded after 2 hours of ex vivo perfusion. Results One day after reperfusion, compared with the Sham group, the IRI group exhibited more severe renal tissue injury, higher tubular injury scores, increased expression of KIM-1, ICAM-1 and vWF, decreased CD31 expression, elevated serum levels of SDC-1 and HS, increased vascular permeability, and higher expression of TNF-α, IL-1β and IL-6. Compared with the IRI group, the IRI+SDX group showed reduced renal tissue injury, lower tubular injury scores, decreased expression of KIM-1, ICAM-1 and vWF, increased CD31 expression, lower serum levels of SDC-1 and HS, decreased vascular permeability, and reduced expression of TNF-α, IL-1β and IL-6 (all P < 0.05). Ten days after reperfusion, renal tissue injury was further alleviated in the IRI+SDX group. Twenty-five days after reperfusion, the IRI+SDX group exhibited decreased expression of TGF-β, α-SMA, and COL-1, as well as reduced collagen deposition area (all P < 0.05). Compared with the HOPE group, the HOPE+SDX group showed increased renal perfusion flow and decreased intrarenal vascular resistance (both P < 0.01). Conclusions Sulodexide may alleviates renal IRI and fibrosis caused by prolonged warm ischemia by inhibiting inflammatory responses and protecting vascular endothelial glycocalyx.
2.Evolution and innovation of preservation fluid for donor liver
Guotao YU ; Yanfeng YIN ; Chuntao YAN ; Guangxu ZOU ; Huangyan ZHANG ; Li MA ; Zongqiang HU
Organ Transplantation 2024;15(1):131-137
Organ preservation fluid could mitigate cold ischemia injury and maintain normal function of the grafts. At present, how to reduce a series of injury caused by cold ischemia of donor liver and improve the preservation quality of grafts are the hot and challenging spots in this field. Currently, preservation fluid in clinical practice has not achieved ideal preservation effect, especially for the protection of marginal donor organs. In the context of severe donor shortage, the key solution is still to explore the optimal preservation protocol for donor liver to prevent grafts from cold ischemia injury. In this article, the mechanism of donor liver injury during cold ischemia, the classification and evolution of donor liver preservation fluid were summarized, the development direction and challenges of donor liver preservation fluid were discussed, aiming to provide novel ideas and references for the research and development of donor liver preservation fluid.
3.Effect of Ginkgo biloba extract on improving hepatic insulin resistance induced by arsenic exposure based on network pharmacology
Zhida HU ; Shiqing XU ; Ruru MENG ; Yanfeng JIA ; Qiyao ZHANG ; Bohao BIAN ; Shurui WANG ; Yang LIU ; Li WANG ; Yanrong GAO
Journal of Environmental and Occupational Medicine 2024;41(7):751-759
Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L−1 NaAsO2 model group (NaAsO2), 50 mg·L−1 NaAsO2+10 mg·kg−1 GBE intervene group (NaAsO2+GBE), and 10 mg·kg−1 GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L−1 NaAsO2, or given intraperitoneal injection of normal saline containing 10 mg·kg−1 GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L−1 NaAsO2 group (NaAsO2), 8 μmol·L−1 NaAsO2 + 200 mg·L−1 GBE intervene group (NaAsO2+GBE), and 200 mg·L−1 GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO2 group exhibited an elevated blood glucose compared to the control group, and the NaAsO2+GBE group showed a decreased blood glucose compared to the NaAsO2 group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO2 group and NaAsO2+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO2 groups compared to the control groups, which was alleviated in the NaAsO2+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO2+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.
4.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.
5.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.
6.Urinary iodine characteristics of children aged 8 to 10 in Jiangxi Province in 2022
Jun SHANGGUAN ; Binghua ZHOU ; Qiang HU ; Meiqin HUANG ; Guai TANG ; Yanfeng GONG ; Zifen LI ; Wenfang PENG
Chinese Journal of Endemiology 2024;43(10):823-825
Objective:To study the urinary iodine levels of children in Jiangxi Province and provide a basis for prevention and treatment of iodine deficiency disorders and scientific iodine supplementation.Methods:From March to July in 2022, a systematic sampling method was used in 99 counties (cities, districts, abbreviated as counties) in Jiangxi Province. One township (street) was selected from each county in five directions: east, west, south, north and middle. One primary school was selected from each township (street), and 40 non boarding children aged 8 - 10 (half male and half female) were selected from each primary school. One random urine sample was collected to test urinary iodine, and the distribution of urinary iodine in different regions, genders, and ages were compared.Results:A total of 19 842 urine samples were collected from children, with a median urinary iodine level of 181.90 μg/L. The median urinary iodine levels of children in different cities ( H = 1 014.05, P < 0.001), genders ( Z = 6.44, P < 0.001) and ages groups ( H = 29.82, P < 0.001) were compared, and the differences were statistically significant. Conclusion:The urinary iodine level of children in Jiangxi Province is at an appropriate level, but the distribution of urinary iodine is uneven among different regions, genders, and ages, indicating that scientific and precise iodine supplementation is necessary for the prevention and treatment of iodine deficiency disorders.
7.Highlights and cutting-edge advances from the 2024 Korean International Gastric Cancer Week(KINGCA WEEK 2024)
Longfei GOU ; Hao CHEN ; Yanfeng HU ; Jiang YU ; Haijun DENG
Chinese Journal of General Surgery 2024;33(10):1705-1713
From September 26 to 28,2024,the 11th Korean International Gastric Cancer Week(KINGCA WEEK 2024),a prestigious academic conference in the field of gastric cancer,was held in Seoul.Organized by the Korean Gastric Cancer Association,the conference featured one main venue,18 sub-venues,and 16 thematic symposiums,including 100 invited presentations and four keynote speeches,attracting 788 experts and scholars from around the world.Additionally,the conference set 16 themes and received 425 submissions from 24 countries,including Republic of Korea,China,Japan,and the United States.After a review process,365 submissions were accepted,which included eight plenary oral presentations,78 oral reports,and 279 poster presentations.The conference covered many hot topics in gastric cancer diagnosis and treatment,with a particular focus on surgical-related areas such as treatment strategies for metastatic gastric cancer,an international consensus meeting on the conversion therapy for stage Ⅳgastric cancer,future research directions of the Korean Laparoendoscopic Gastrointestinal Surgery Study Group,the development of new surgical instruments and equipment,and key issues in lymph node dissection,resection,and reconstruction during minimally invasive gastric cancer surgeries.Furthermore,our team was invited to present two oral reports on"the application of artificial intelligence in minimally invasive gastric cancer surgery".This report aims to detail the dynamics and hotspots related to surgical treatment for gastric cancer,providing valuable references and insights for domestic surgical peers.
8.Visualization and hotspots analysis of research on adenocarcinoma of esophagogastric junc-tion based on Web of Science
Lin LIU ; Zhongyi WANG ; Chuyin HUANG ; Yanfeng HU ; Jiang YU ; Guoxin LI ; Hao CHEN
Chinese Journal of Digestive Surgery 2023;22(10):1243-1254
In recent years, the incidence of adenocarcinoma of esophagogastric junction (AEG) has increased gradually. Due to the unique anatomical location and the different biological features from esophageal cancer and gastric cancer, AEG cannot be simply equated with esophageal cancer or gastric cancer, and the definition, classification and treatment methods of AEG are still controversial. As a result, the study of AEG is becoming increasingly important. Using bibliometrics, the authors search English literatures from the Web of Science Core Collection database from the establishment to December 31, 2022, with the keyword adenocarcinoma of esophagogastric junc-tion. To systematically review the international literatures on AEG, EndNote and Excel are used to manage literatures and perform statistical analysis, and VOSviewer and CiteSpace are used to analyze the social network, time series of countries, institutions, authors and keywords, the co-citation of authors and the citation bursts of keywords. The authors summarize the research status and hot trends in this field, hoping to provide reference for future research.
9.Application value of mixed reality technology in surgical conversation of laparoscopy radical resection of gastric cancer: a prospective study
Yuxuan YANG ; Weihong GUO ; Guoxin LI ; Jiang YU ; Mingli ZHAO ; Tao CHEN ; Zhian CHEN ; Yiping CHEN ; Wenfei LIU ; Yanfeng HU
Chinese Journal of Digestive Surgery 2023;22(3):414-418
Objective:To investigate the application value of mixed reality technology in surgical conversation of laparoscopy radical resection of gastric cancer.Methods:The prospective randomized controlled study was conducted. There were 80 family members of patients with gastric cancer who were admitted to Nanfang Hospital of Southern Medical University from June 2021 to December 2022 being selected as subjects. All patients underwent laparoscopic radical resection of gastric cancer. Based on random number table, all subjects were allocated into the control group and the experiment group. Subjects in the control group performed routine surgical conversation and subjects in the experiment group performed surgical conversation based on mixed reality technology. Observation indicators: (1) baseline data of the subjects; (2) anxiety assessment of the subjects. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for inter-group comparison. Repeated measurement data were analyzed using the repeated ANOVA. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. Results:(1) Baseline data of the subjects. A total of 80 subjects were selected for eligibility, including 40 subjects in the control group and 40 subjects in the experi-ment group. There were 44 males and 36 females, aged (40±9)years. The gender (male, female), age, education background (primary school education, middle school education, high school education, junior college education, undergraduate education, postgraduate education) were 23, 17, (39±9)years, 1, 3, 9, 16, 9, 2 in subjects of the control group, versus 25, 15, (42±10)years, 0, 8, 6, 11, 14, 1 in subjects of the experiment group, showing no significant difference in the above indicators between the two groups ( χ2=0.20, t=?1.64, Z=?0.10, P>0.05). (2) Anxiety assessment of the subjects. The scores of self-rating Anxiety Scale (SAS) and Hospital Anxiety Scale (HADS) before surgical conversation, after surgical conversation, after surgery were 41±10 and 26±5, 49±11 and 32±3, 40±13 and 15±8 in subjects of the control group, versus 44±9 and 23±3, 66±16 and 28±6, 34±14 and 8±3 in subjects of the experiment group, showing significant differences in the above indicators between the two groups ( FSAS组间=8.83, FSAS时间=40.41, FSAS交互=12.21, FHADS组间=32.42, FHADS时间=321.28, FHADS交互=6.15, P<0.05). Conclusion:Compared with traditional surgical conversation, mixed reality technology based surgical conversation can relieve the postoperative conxiety of subjects.
10.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73

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