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.Sishenwan Restores Intestinal Barrier in Rat Model of Diarrhea-predominant Irritable Bowel Syndrome Due to Spleen-kidney Yang Deficiency by Regulating Intestinal Flora and Short-chain Fatty Acids
Qian ZHANG ; Siqi LI ; HUYUNLIAN ; Na WEN ; Chaoqun HUANG ; Binbin LIU ; Chengxia SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):80-89
ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats, 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank, model, low-dose (3.51 g·kg-1) Sishenwan, high-dose (7.02 g·kg-1) Sishenwan, and Peifeikang (0.54 g·kg-1) groups, with 8 rats in each group. The blank group was fed conventionally, and the other groups were subjected to mother-child separation and Sennae Folium gavage (1 g·mL-1, 10 mL·kg-1) for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed, the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage, and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration, the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta (TGF-β), interleukin-10 (IL-10), and interleukin-22 (IL-22). Immumohistochemical staining (IHC) was performed to detect the positive expression of zonula occludens-1 (ZO-1) and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats, and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids (SCFAs) in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure, neat glands, and no inflammatory cell infiltration. In the model group, the colon tissue showcased a disorganized structure, irregular arrangement of glands, and inflammatory cell infiltration. Compared with the model group, the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure, regular arrangement of glands, and reduced inflammatory cell infiltration. Compared with the blank group, the modeling lowered the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.01), down-regulated the protein levels of ZO-1 and occludin in the colon tissue (P<0.01), and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents (P<0.05). Compared with the model group, low-dose and high-dose Sishenwan raised the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.05, P<0.01), and Peifeikang elevated the levels of TGF-β and IL-10 in the serum (P<0.01). High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin (P<0.05, P<0.01), increased the content of acetic acid and propionic acid in cecum contents (P<0.05), and decreased the content of butyric acid (P<0.05). The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group, Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae, Muribaculaceae, Akkermansiaceae, Ligilactobacillus, UBA3282, Akkermansia, and Corynebacterium while reducing the relative abundance of Oscillospiraceae, Desulfovibrionaceae, Lactobacillus, Romboutsia, and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation, increase the expression of tight junction proteins in the colonic mucosa, and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs, and the effect of high-dose Sishenwan is obvious.
3.Sishenwan Restores Intestinal Barrier in Rat Model of Diarrhea-predominant Irritable Bowel Syndrome Due to Spleen-kidney Yang Deficiency by Regulating Intestinal Flora and Short-chain Fatty Acids
Qian ZHANG ; Siqi LI ; HUYUNLIAN ; Na WEN ; Chaoqun HUANG ; Binbin LIU ; Chengxia SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):80-89
ObjectiveTo investigate the effect and mechanism of Sishenwan in restoring the intestinal barrier function in the rat model of diarrhea-predominant irritable bowel syndrome (IBS-D) due to spleen-kidney Yang deficiency based on intestinal flora and short-chain fatty acids. MethodsAfter the delivery of 10 SPF-grade pregnant rats, 4 male suckling rats were kept in each litter for the experiment. The male suckling rats were randomly allocated into blank, model, low-dose (3.51 g·kg-1) Sishenwan, high-dose (7.02 g·kg-1) Sishenwan, and Peifeikang (0.54 g·kg-1) groups, with 8 rats in each group. The blank group was fed conventionally, and the other groups were subjected to mother-child separation and Sennae Folium gavage (1 g·mL-1, 10 mL·kg-1) for the modeling of IBS-D due to spleen-kidney Yang deficiency. After the modeling was completed, the rats in Sishenwan groups were administrated with the corresponding dose of Sishenwan decoction by gavage, and the Peifeikang group with bifidobacterium triple live powder+normal saline suspension. The blank and model groups were treated with an equal volume of normal saline by gavage. The general conditions and fecal characteristics of rats were observed. After 2 weeks of administration, the rats were anesthetized for sample collection. The pathological changes of the colon tissue in rats were observed by hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to measure the levels of transforming growth factor-beta (TGF-β), interleukin-10 (IL-10), and interleukin-22 (IL-22). Immumohistochemical staining (IHC) was performed to detect the positive expression of zonula occludens-1 (ZO-1) and occludin in the colon tissue. Western blot was employed to determine the protein levels of ZO-1 and occludin in the colon tissue of rats, and 16S rRNA gene sequencing was performed for intestinal flora. Gas chromatography-mass spectrometry was employed to determine the content of short-chain fatty acids (SCFAs) in the cecum contents of rats. ResultsThe colon tissue in the blank group presented a clear structure, neat glands, and no inflammatory cell infiltration. In the model group, the colon tissue showcased a disorganized structure, irregular arrangement of glands, and inflammatory cell infiltration. Compared with the model group, the low-dose and high-dose Sishenwan groups and the Peifeikang group exhibited an intact colon tissue structure, regular arrangement of glands, and reduced inflammatory cell infiltration. Compared with the blank group, the modeling lowered the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.01), down-regulated the protein levels of ZO-1 and occludin in the colon tissue (P<0.01), and decreased the content of acetic acid and propionic acid and increased the content of butyric acid in cecum contents (P<0.05). Compared with the model group, low-dose and high-dose Sishenwan raised the levels of TGF-β, IL-10, and IL-22 in the serum (P<0.05, P<0.01), and Peifeikang elevated the levels of TGF-β and IL-10 in the serum (P<0.01). High-dose Sishenwan and Peifeikang up-regulated the protein levels of ZO-1 and occludin (P<0.05, P<0.01), increased the content of acetic acid and propionic acid in cecum contents (P<0.05), and decreased the content of butyric acid (P<0.05). The 16S rRNA gene sequencing results showed that the intestinal flora structure of the model group changed compared with that of the blank group. Compared with the model group, Sishenwan and Peifeikang increased the relative abundance of Lachnospiraceae, Muribaculaceae, Akkermansiaceae, Ligilactobacillus, UBA3282, Akkermansia, and Corynebacterium while reducing the relative abundance of Oscillospiraceae, Desulfovibrionaceae, Lactobacillus, Romboutsia, and Desulfovibrio. They can restore the intestinal flora structure similar to that in the blank group. ConclusionSishenwan can alleviate diarrhea symptoms and colonic mucosal inflammation, increase the expression of tight junction proteins in the colonic mucosa, and strengthen the intestinal barrier in IBS-D rats with the syndrome of spleen-kidney Yang deficiency. The mechanism of action may be related to optimizing the structure and balance of intestinal flora and regulating the SCFAs, and the effect of high-dose Sishenwan is obvious.
4.A Comparative Study of Three Methods of Preventing Intrauterine Adhesions after HEOS
Liyan MENG ; Junli GAO ; Chunlin LI ; Jie NIU ; Yan SUN ; Chaoqun WANG
Journal of Kunming Medical University 2024;45(2):141-147
Objective To compare the efficacy of three different methods in the prevention of adhesion after the HEOS system for different degrees of intrauterine adhesions.Methods 284 patients with mild,moderate and severe intrauterine adhesions,who were treated with the HEOS system,were divided into three groups,the intrauterine device with sodium hyaluronate gel was placed in Group A,Foley water capsule tube with sodium hyaluronate gel was placed in Group B,and sodium hyaluronate gel was placed in Group C only.The recovery of uterine adhesion,improvement of menstruation,endometrial thickness,and adverse reactions were compared among the three groups.Results The mild intrauterine adhesions group showed statistical differences among the three groups(P<0.05).Group A had a higher menstrual improvement rate than Group C(P<0.017),and there was no significant difference in other therapeutic indicators(P>0.017).However,the adverse reaction rate in Group A was also higher than that in Group C(P<0.017).In the moderate intrauterine group,there was a significant difference in the improvement rate of intrauterine adhesions between Group B and the other two groups(P<0.017).Group A and B were higher than Group C in terms of menstrual status,endometrial thickness,and adverse reactions(P<0.017).In severe intrauterine adhesions,Group A had higher efficacy indicators than other groups(P<0.017).Conclusions The curative effect index and adverse reaction rate were analyzed,after operation.For the light,moderate,and severe intrauterine adhesions,sodium hyaluronate gel,Foley water capsule tube with sodium hyaluronate gel,and intrauterine device with sodium hyaluronate gel were the best choice for adhesion.Individual and hierarchical management can achieve good clinical effects,which is worth popularizing.
5.Construction and application of an injectable cartilage graft
Chaoqun MA ; Haiqiang LI ; Wei WU
Journal of Practical Stomatology 2024;40(1):20-25
Objective:To explore a set of procedures for the effictive granulation of cartilage,and to construct injectable cartilage graft with platelet-rich gel(PRG),and to evaluate its effects in nude mice models.Methods:The costal cartilage of adult male rab-bits was cut into pieces and placed in a mortar for 30-60 s freezing in liquid nitrogen and grinding for a short time to obtain granular cartilage.Blood was collected from the middle ear artery and PRG was prepared by double centrifugation.Granular cartilage and the mixture of granular cartilage and PRG were injected subcutaneously in nude mice of control group(n=5)and experimental group(n=5)respectively.8 weeks after injection,the gross morphology observation and histological examination were pertormed.The nasal dor-sum augmentation model of nude mice was established in the experimental group.Results:The cartilage particles were in the size of 10-500 pm in diameter after frozen grinding,and injection could be realized.In vitro culture showed that the cell survival rate of granular cartilage reached to 80%.In vivo test showed that the sample morphology of the control group was insignificant,and the sur-face was grainy.That of the experimental group was well maintained,and the surface was smooth with obvious capillaries.The sam-ples of experimental group achieved significant augmentation in the nude mouse model of nasal dorsum augmentation.Conclusion:Freeze-milling technology can achieve efficient granulation of cartilage,and the graft constructed with PRG gel is suitable for maxillo-facial cartilage transplantation repair.
6.Characteristics and significance of age-related changes in cervical uncinate process-related angle
Dezhou ZHANG ; Chaoqun WANG ; Jun SHI ; Kun LI ; Shaojie ZHANG ; Yuan MA ; Erfei HOU ; Danyang ZHAO ; Yunteng HAO ; Simin WANG ; Xiaohe LI ; Haiyan WANG ; Zhijun LI ; Xing WANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5766-5772
BACKGROUND:As a unique structure of the cervical spine,the occurrence,development and progression of the uncovertebral joint directly affect the stability and range of motion of the cervical spine,and are also closely related to the pathogenesis of cervical spondylosis.A thorough understanding of the developmental characteristics of the uncovertebral joint is of great significance for the pathogenesis,diagnosis,and treatment of cervical spondylosis. OBJECTIVE:By using imaging and three-dimensional reconstruction technology to measure and observe the cervical uncinate process-related angle in a large sample of different age groups,the aim is to reveal the characteristics of its changes with age and vertebral growth,as well as its relationship with cervical spine stability. METHODS:Using a retrospective research design,we collected 1 447 cases of raw CT imaging data that meet the study requirements for complete cervical spine segments.The raw data were imported into Mimics 21.0 software in DICOM format for post-processing and measurement of angle of uncinate process and sagittal angle of uncinate process.The data were grouped based on gender,age,and side. RESULTS AND CONCLUSION:(1)With the increase of vertebral sequence,the angle of uncinate process increased in a V-shaped shape,and the lowest peak was at C5.The overall population showed a sharp peak with the increase of age,and the peak value mostly occurred in the age range of 30-39 years.(2)The sagittal angle of the uncinate process increased like a fishhook with the increase of the vertebral sequence,and the overall angle of the uncinate process increased with age,and the peak value mostly occurred in the age range of 20-29 years.The uncinate process angle and sagittal angle showed only partial significant differences between sides and genders(P<0.05).(3)It is concluded that the angle of the uncinate process increased with the increase of vertebral sequence in a V-shaped manner.The sagittal angle of the uncinate process increases like a fish hook with increasing vertebral order,while the two angles generally peak with increasing age.The angle of the uncinate process is about 131°,which may be closely related to the stability of the cervical spine,while the sagittal angle of the uncinate process is about 14°,and its function may play a certain role in limiting the excessive rotation of the cervical spine.
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.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.
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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