1.Progress on the mechanisms of prevention and treatment of radiation-induced intestinal injury using Chinese medicine monomers and application of nanotechnology for enhanced efficiency
Lei CHEN ; Zekun LI ; Chaoqun PI ; Yang HE ; Ming LI
Chinese Journal of Radiological Health 2025;34(4):614-624
Radiation-induced intestinal injury is caused by high dose of radiation in the abdomen and pelvis. The disease is characterized by complicated pathological mechanisms and poses significant challenges to clinical treatment, seriously affecting the quality of life and health of patients. Current treatments in modern medicine offer limited efficacy and are often associated with adverse side effects. Traditional Chinese medicine monomers inhibit inflammatory factors (e.g., tumor necrosis factor-α and interleukin-1β) and regulate the antioxidant enzyme system (e.g., improving the activity of superoxide dismutase) to effectively reduce the symptoms of radiation-induced intestinal injury with minimal side effects. Through targeted delivery of nanoparticles, nanotechnology can accurately deliver the active ingredients of traditional Chinese medicine to damaged intestinal tissues, thus improving their bioavailability and therapeutic effects. This paper reviews the mechanisms of Chinese medicine monomers in the prevention and treatment of radiation-induced intestinal injury and the application of nanotechnology for enhanced efficiency. The paper also discusses the clinical potential of these approaches. These results provide a reference for future research and clinical practice.
2.National bloodstream infection bacterial resistance surveillance report(2022): Gram-positive bacteria
Chaoqun YING ; Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(2):99-112
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units,and the top five bacteria were Staphylococcus aureus( n=1 147,36.3%),coagulase-negative Staphylococci( n=928,29.3%), Enterococcus faecalis( n=369,11.7%), Enterococcus faecium( n=296,9.4%)and alpha-hemolyticus Streptococci( n=192,6.1%). The detection rates of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)were 26.4%(303/1 147)and 66.7%(619/928),respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome,rifampin,compound sulfamethoxazole,linezolid,minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%(2/369),and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions( χ2=14.578, P=0.002),while the detection rate of MRCNS in northern China was significantly higher than that in other regions( χ2=15.195, P=0.002). The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals( χ2=13.519 and 12.136, P<0.001). The detection rates of MRSA and MRCNS in economically more advanced regions(per capita GDP≥92 059 Yuan in 2022)were higher than those in economically less advanced regions(per capita GDP<92 059 Yuan)( χ2=9.969 and 7.606, P=0.002和0.006). Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China, Staphylococci is the most common while the MRSA incidence decreases continuously with time;the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China,with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.
3.Effect of MDT supervision model in the construction of incorruptible hospital under the new situation
Xuefei WANG ; Chaoqun CHEN ; Xiaoying WANG
Modern Hospital 2024;24(5):670-673
Under the new national initiative to rigorously rectify corruption in the medical field,the Discipline Inspection and Supervision Office of the Children's Hospital,Zhejiang University School of Medicine has adopted a multidisciplinary team(MDT)supervision model.Drawing on multidisciplinary administrative practices,the hospital has developed a strategy centered around the establishment of integrity-focused departments and the conduct of work style inspections.This approach is designed to promote the fulfillment of the Party committee's primary responsibility in building a clean and disciplined Party,as well as the supervisory responsibilities of the discipline inspection commission.The model employs a full-process closed-loop management system,which involves identifying issues,urging for corrective actions,and refining systems to ensure accountability and trans-parency.Significant achievements have been made in strengthening the responsibility system,preventing corruption,bolstering work style construction,and delivering targeted anti-corruption education.
4.Feasibility and safety of Da Vinci robotic-assisted thoracoscopy in pediatric mediastinal tumor resection
Huifang LIU ; Li WANG ; Fan DONG ; Chaoqun HU ; Demei CHEN ; Li FAN
The Journal of Practical Medicine 2024;40(13):1840-1845
Objective This study aims to investigate the feasibility and safety of Da Vinci robotic-assisted thoracoscopy for resecting mediastinal tumors in pediatric patients.Methods From November 2020 to June 2023,a total of 80 pediatric patients undergoing mediastinal tumor resection at Wuhan Children's Hospital were randomly assigned into two groups,with each group consisting of 40 participants.The control group underwent conventional thoracoscopy,while the observation group underwent Da Vinci robotic-assisted thoracoscopy.This study aimed to compare perioperative indicators between the two groups and establish learning curves based on surgical duration and intraoperative blood loss.Additionally,it assessed levels of pain mediators and stress response markers before surgery and at 24 hours post-surgery,as well as postoperative complications.Inflammatory marker levels were evaluated one month after surgery,and the children's quality of life was measured using the Pediatric Quality of Life Inventory(PedsQL)Generic Core Scales before surgery and one month post-surgery.Results The surgical duration for the observation group and the control group was(1.76±0.33)hours and(2.82±0.62)hours,respectively,and the intraoperative blood loss was(49.83±6.39)mL and(71.55±8.19)mL,respectively.Furthermore,the post-operative drainage time,drainage volume,and hospital stay for the observation group were all lower than those for the control group(P<0.05).After surgery,the levels of BK,5-HT,NPY,and PGE2 in the observation group were(8.06±1.06)mg/L,(170.20±13.21)ng/L,(201.82±13.52)mg/L,and(241.82±15.32)ng/L,respectively,indicating lower levels of pain mediators,stress response markers,and inflammatory factors compared to the control group(P<0.05).he overall incidence of complications was 2.50%in the observation group as opposed to 20.00%in the control group.Moreover,there was a statistically significant improvement in quality of life after surgery within the observation group when compared to that within the control group(P<0.05).Conclusion Da Vinci robotic-assisted thoracoscopy demonstrates enhanced feasibility and safety in pediatric mediastinal tumor resection,thereby justifying its clinical promotion.
5.99Tcm-MIBI Bone Uptake on Hungry Bone Syndrome in Renal Hyperparathyroidism After Parathyroidectomy
Zejun CHEN ; Bin ZHOU ; Jingjing FU ; Chaoqun WU ; Qing SHAO ; Qianhuan HUANG ; Feng WANG
Chinese Journal of Medical Imaging 2024;32(7):669-673
Purpose To investigate the value of 99Tcm-(methoxyisobutvlisonitrile,MIBI)bone uptake on hungry bone syndrome(HBS)in renal secondary hyperparathyroidism(SHPT)after parathyroidectomy.Materials and Methods From June 2014 to December 2021,106 renal SHPT patients who underwent successful parathyroidectomy in Jiangyin Hospital Affiliated Nantong University were retrospectively enrolled.Visual analysis was used to evaluate the abnormal bone uptake of 99Tcm-MIBI.The patients were divided into HBS group and non-HBS group based on whether occurred HBS.The clinical features,laboratory indicators and 99Tcm-MIBI bone uptake were compared between the two groups.Results Of 106 renal SHPT patients,42(39.62%)patients with bone uptake on visual assessment,showed diffusely increased tracer accumulation,particularly in sternum,clavicle and ribs.The age in HBS group was younger than that in non-HBS group(t=-3.058),the alkaline phosphatase and parathyroid hormone level in HBS group were higher than that in non-HBS group(Z=-5.148,-2.218),the serum corrected calcium in HBS group was lower than that in non-HBS group(Z=-2.102),the positive rate and number of 99Tcm-MIBI bone uptake in HBS group was 50%and 2(1,3),which was higher than that of 28%and 1(1,1)in non-HBS group(χ2=5.344,Z=-2.970),respectively,all showed statistically significant difference(all P<0.05).Conclusion Renal SHPT patient with HBS after parathyroidectomy is commonly related to a high level of alkaline phosphatase and parathyroid hormone,and more likely to develop abnormal 99Tcm-MIBI bone uptake.
6.Efficacy and prognostic survival analysis of pembrolizumab combined with apatinib and chemotherapy in treating human epidermal growth factor receptor-2-negative advanced gastric cancer
Hongmei XU ; Tao ZHOU ; Lanlan CHEN ; Lifang GUAN ; Liming GAO ; Chaoqun WANG
Clinical Medicine of China 2024;40(6):408-414
Objective:To investigate the efficacy and prognostic survival of pembrolizumab combined with apatinib and chemotherapy in the treatment of human epidermal growth factor receptor-2 (HER2)-negative advanced gastric cancer.Methods:Patients with HER2-negative advanced gastric cancer were selected from December 2019 to December 2022 as the study subjects. Forty-five patients who received chemotherapy therapy (fluorouracil+cisplatin) were randomly collected and included in control group, and 52 patients who were treated with pembrolizumab combined with apatinib were randomly selected and enrolled as observation group. The difference in short-term efficacy was compared. The levels of serum tumor markers and immune function (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) were recorded. The long-term efficacy and adverse reactions of patients were compared. Measurement data conforming to the normal distribution were expressed as xˉ± s, and the mean comparison between groups was performed by independent sample t test. Chi-square test was used to compare the rate or composition ratio among enumeration data. P<0.05 was considered statistically significant. Results:At 6 months after treatment, the disease control rate in observation group was significantly higher than that in control group (78.85% (41/52) vs 57.78% (26/45)) ( χ2=5.01, P=0.025), but there was no statistical significance in objective response rate between groups (36.54% (19/52) vs 24.45% (11/45)) ( χ2=1.65, P=0.199). The levels of pepsinogen I, tissue polypeptide specific antigen, carcinoembryonic antigen, carbohydrate antigen 199 and CD8 + in both groups were reduced after treatment, and the levels were lower in observation group than those in control group ( t=6.06, 6.78, 4.68, 11.21, 3.45, all P<0.001). The levels of CD3 +, CD4 + and CD4 +/CD8 + were enhanced significantly in the two groups, and the observation group had higher levels after treatment ( t values were 2.10, 3.74, and 5.19; P values were 0.028, <0.001, and <0.001). After 1 year of follow-up, the survival rate in observation group with 59.62% (31/52) was significantly higher than 37.78% (17/45) in control group ( χ2=4.60, P=0.032). The progression-free survival time ((10.22±1.62) months vs (8.13±1.57) months, t=6.43, P<0.001) and overall survival time ((11.62±1.84) months vs (9.73±1.71) months, t=5.21, P<0.001) in observation group were significantly longer compared to control group. There were no statistical differences in the incidence rates of bone marrow suppression ( χ2=1.92, P=0.165), hand-foot syndrome ( χ2=3.47, P=0.062), gastrointestinal reaction ( χ2=0.32, P=0.574), hypertension ( χ2=0.94, P=0.333) and proteinuria ( χ2=2.39, P=0.122) between the two groups. Conclusion:Compared with chemotherapy, pembrolizumab combined with apatinib shows good short-term efficacy and long-term efficacy in patients with HER2-negative advanced gastric cancer.
7.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
8.The mechanism of Bufei Tongbi Decoction in treatment of systemic lupus erythematosus interstitial lung disease based on network pharmacology and verification of key regulation pathway
Shangwen WU ; Huan LI ; Xiaohong GONG ; Chaoqun LU ; Yiming CHEN ; Ximeng LI ; Yan LI ; Songwei LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1256-1271
Objective To explore the effect and possible pharmacological mechanism of Bufei Tongbi Decoction in the treatment of systemic lupus erythematosus interstitial lung disease (SLE-ILD).Methods The effective components and related targets of Bufei Tongbi Decoction were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Uniprot database. Key genes for SLE-ILD were screened based on DrugBank,DisGeNET,GeneCards,PharmGKB,OMIM,and GEO databases. Using Cytoscape software,a drug active ingredient-target-disease relationship network diagram was constructed to obtain the effective active ingredients and possible mechanisms of action of Bufei Tongbi Decoction in the treatment of SLE-ILD. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal related target genes and pathway functions. Taking C57BL/6 mice as normal group,MRL/lpr mice were injected with bleomycin 5mg/kg in the nasal cavity. According to the random number table method,the mice were divided into model group,Bufei Tongbi Decoction low-dose group (10.4 g/(kg·d)),Bufei Tongbi Decoction medium-dose group (20.8 g/(kg·d)),Bufei Tongbi Decoction high-dose group (41.6 g/(kg·d)) and prednisone group (3 mg/(kg·d)). The intervention lasted for 28 days. Hematein eosin and Masson staining were used to observe the pathological changes of mouse lung tissue,the expressions of transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Col-Ⅲ) in lung tissue were detected by immunohistochemistry,and the expressions of interleukin-1β(IL-1β),interleukin-10 (IL-10) and interleukin-17 (IL-17) in serum were detected by ELISA. The mRNA expressions of matrix metallopeptidase 1(MMP-1),hypoxia inducible factor-1α(HIF-1α),retinoid-related orphan receptor γt (RORγt ) and forkhead box P3 (FOXP3) in lung tissue were analyzed by RT-PCR,the protein expressions of HIF-1α and MMP-1 in lung tissue were detected by Western blotting,and the expressions of T helper 17 cells (Th17) and regulatory T cells (Treg cells) in blood were detected by cytometry.Results A total of 163 effective ingredients,259 targets,1729 SLE-ILD disease targets,958 SLE-ILD differential genes and 40 drug-disease interaction targets were obtained by screening. GO functional enrichment and KEGG pathway enrichment showed that IL-17 signaling pathway activated by IL-1β and MMP-1,and Th17 cell differentiation activated by IL-1β and HIF-1α were the main pathways. Animal experiments showed that Bufei Tongbi Decoction could effectively improve the degree of lung interstitial lesion and reduce the expressions of TGF-β1 and Col-Ⅲ in SLE-ILD mice (P<0.01). The expressions of IL-1β,HIF-1α and IL-17 were decreased (P<0.01). Medium and high doses of Bufei Tongbi Decoction decreased the expressions of MMP-1 and RORγt mRNA (P<0.01),and increased the expressions of IL-10 and FOXP3 mRNA (P<0.01). Bufei Tongbi Decoction could reduce the proportion of Th17 cells,increase the proportion of Treg cells,downregulate the balance of Th17/Treg (P<0.05),and improve the immune disorder. Conclusion Bufei Tongbi Decoction has the characteristics of multi-target and multi-pathway in treating SLE-ILD,and its mechanism may be related to the regulation of Th17/Treg cell balance.
9.A genetic variant in the immune-related gene ERAP1 affects colorectal cancer prognosis
Danyi ZOU ; Yimin CAI ; Meng JIN ; Ming ZHANG ; Yizhuo LIU ; Shuoni CHEN ; Shuhui YANG ; Heng ZHANG ; Xu ZHU ; Chaoqun HUANG ; Ying ZHU ; Xiaoping MIAO ; Yongchang WEI ; Xiaojun YANG ; Jianbo TIAN
Chinese Medical Journal 2024;137(4):431-440
Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)
10.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.

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