1.Mechanism of Huangqi Chifengtang in Treating Atherosclerosis Based on 16S rRNA Sequencing and Metabolomics
Yuqin LIANG ; Jiaqi FU ; Yunhe SHI ; Fang LU ; Donghua YU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):94-103
ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang (HQCFT) on rats with atherosclerosis (AS) by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D3 injection, and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups: A blank group, a model group, a group receiving a low dose of HQCFT at 1.53 g·kg-1 (HQCFT-L group), a group receiving a high dose of HQCFT at 3.06 g·kg-1 (HQCFT-H group), and a group receiving atorvastatin calcium tablets at 1.8 mg·kg-1 (Ato group), with 10 rats in each group. Oral gavage administration started on the day after model establishment, once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin (HE) staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction (Real-time PCR) was used for detecting inflammatory factor levels in the aorta, high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents, targeted metabolomics for detecting short-chain fatty acid (SCFA) levels, and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group, the aortic tissue of rats in the model group showed significant AS lesions, including endothelial damage, inflammatory infiltration, and formation of fibrous plaques and calcified foci. Moreover, serum triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated (P<0.05), while high-density lipoprotein cholesterol (HDL-C) levels were significantly reduced (P<0.05). Significant increases were observed in whole blood viscosity, plasma viscosity, and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, interleukin (IL)-β, IL-6, and tumor necrosis factor-α (TNF-α) in aortic tissue (P<0.05). Additionally, gut microbiota composition, SCFA levels, and metabolomic profiles were significantly altered. Compared with those in the model group, serum TC, TG, and LDL-C levels, as well as the whole blood viscosity and plasma viscosity, were significantly reduced in all groups treated with HQCFT (P<0.05). Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT, Caspase-1, IL-β, and IL-6 mRNA expression levels in the HQCFT-H group, and TNF-α mRNA expression levels in the HQCFT-L group (P<0.05). HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid, valeric acid, and propionic acid. Non-targeted metabolomics identified 39 differential metabolites, which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition, promoting SCFA production, and regulating the levels of metabolites in intestinal contents.
2.Mechanism of Huangqi Chifengtang in Treating Atherosclerosis Based on 16S rRNA Sequencing and Metabolomics
Yuqin LIANG ; Jiaqi FU ; Yunhe SHI ; Fang LU ; Donghua YU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):94-103
ObjectiveTo investigate the mechanism of action of Huangqi Chifengtang (HQCFT) on rats with atherosclerosis (AS) by regulating the gut microbiota and their metabolites. MethodsA rat model of AS was induced through high-fat diet feeding and vitamin D3 injection, and the modeling lasted for 12 weeks. Fifty eight-week-old male SD rats were randomly divided into five groups: A blank group, a model group, a group receiving a low dose of HQCFT at 1.53 g·kg-1 (HQCFT-L group), a group receiving a high dose of HQCFT at 3.06 g·kg-1 (HQCFT-H group), and a group receiving atorvastatin calcium tablets at 1.8 mg·kg-1 (Ato group), with 10 rats in each group. Oral gavage administration started on the day after model establishment, once daily for four weeks. The efficacy of HQCFT was verified using aortic hematoxylin-eosin (HE) staining and determination of lipid levels and hemorrheology. The real-time polymerase chain reaction (Real-time PCR) was used for detecting inflammatory factor levels in the aorta, high-throughput sequencing for analyzing the gut microbiota composition in intestinal contents, targeted metabolomics for detecting short-chain fatty acid (SCFA) levels, and non-targeted metabolomics for identifying metabolomic profiles of intestinal contents. ResultsCompared with that in the blank group, the aortic tissue of rats in the model group showed significant AS lesions, including endothelial damage, inflammatory infiltration, and formation of fibrous plaques and calcified foci. Moreover, serum triacylglycerol (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated (P<0.05), while high-density lipoprotein cholesterol (HDL-C) levels were significantly reduced (P<0.05). Significant increases were observed in whole blood viscosity, plasma viscosity, and the mRNA expression levels of NOD-like receptor pyrin domain containing 3 (NLRP3), Caspase-1, interleukin (IL)-β, IL-6, and tumor necrosis factor-α (TNF-α) in aortic tissue (P<0.05). Additionally, gut microbiota composition, SCFA levels, and metabolomic profiles were significantly altered. Compared with those in the model group, serum TC, TG, and LDL-C levels, as well as the whole blood viscosity and plasma viscosity, were significantly reduced in all groups treated with HQCFT (P<0.05). Significant decreases were observed in NLRP3 mRNA expression levels in all groups treated with HQCFT, Caspase-1, IL-β, and IL-6 mRNA expression levels in the HQCFT-H group, and TNF-α mRNA expression levels in the HQCFT-L group (P<0.05). HQCFT reversed the increase in the F/B ratio and dialled back the decrease in the relative abundance of Blautia and the increase in that of Desulfovibrio. HQCFT promoted the production of acetic acid, valeric acid, and propionic acid. Non-targeted metabolomics identified 39 differential metabolites, which were mainly enriched in metabolic pathways such as arachidonic acid metabolism and primary bile acid biosynthesis. ConclusionThe mechanism by which HQCFT ameliorates AS injury may be related to the improvement of dyslipidemia and body inflammatory responses by altering gut microbiota composition, promoting SCFA production, and regulating the levels of metabolites in intestinal contents.
3.Key points and technical difficulties of radical gastrectomy for locally advanced gastric cancer after neoadjuvant therapy
Yunhe GAO ; Yawen CHEN ; Peifa LIU ; Zhi QIAO
International Journal of Surgery 2024;51(5):289-293
China is a major country for gastric cancer incidence, with the majority being at the advanced stage. Currently, there has been a profound change in the perioperative diagnosis and treatment mode of locally advanced gastric cancer. It has become a gradually recommended diagnostic and treatment process in both eastern and western countries gastric cancer guidelines for patients to undergo radical surgery for gastric cancer after neoadjuvant therapy, followed by postoperative adjuvant therapy. Neoadjuvant therapy can downregulate the tumor grade and clinical stage of gastric cancer, facilitating the successful conduct of radical surgery for gastric cancer. Moreover, it allows for further therapeutic selection based on treatment response and empirically guides adjuvant therapy. However, after neoadjuvant therapy, tumor tissue and the whole body of the patient will inevitably undergo a series of changes, which will affect the implementation process of radical surgery for gastric cancer and postoperative management. Therefore, this article intends to discuss the indications and progress of neoadjuvant therapy for gastric cancer, the timing of radical surgery, technical points, postoperative complications, and other aspects, in order to provide reference and guidance for colleagues in the industry.
4.The clinical application of single-incision transobturator bulbourethral sling suspension without skin tunnel puncture in male patients with urinary incontinence
Lingfeng MENG ; Jipeng WANG ; Jibo JING ; Miao WANG ; Huimin HOU ; Yunhe ZHOU ; Yaoguang ZHANG ; Jianye WANG
Chinese Journal of Urology 2024;45(9):681-685
Objective:To explore the efficacy and safety of single-incision transobturator bulbourethral sling suspension without skin tunnel puncture in male patients with urinary incontinence.Methods:The clinical data of 6 male patients with urinary incontinence who underwent single-incision transobturator bulbourethral sling suspension without skin tunnel puncture in Beijing Hospital from August 2023 to August 2024 were retrospectively analyzed.The age of the patients ranged from 66 to 76 years old, with an average of 71.7 years old. The disease duration ranged from 18 to 48 months, with an average of 30 months. Six patients used 1 to 3 pads per day, with an average of 2.3 pads. The International Continence Incontinence Questionnaire Short Form (ICI-Q-SF) scored 13 to 19, with an average of 15.8. The Incontinence Quality of Life Questionnaire (I-QOL) scored 5.3 to 30.6, with an average of 18.8. Three patients underwent transurethral resection of the prostate for benign prostatic hyperplasia and three patients underwent radical prostatectomy for prostate cancer. The degree of urinary incontinence was mild in 2 cases and moderate in 4 cases. The technical points are as follows: the puncture method has been changed from the traditional outside-in approach to an inside-out approach. After the puncture needle passes through from beneath the skin at the incision, the sling is guided in, avoiding the need for skin tunneling punctures. Upon completion of the puncture, the ends of the sling on both sides are tied with a certain tension at the midline of the incision, and the incision is then closed layer by layer. The efficacy and safety of surgery were evaluated by recording the number of daily pad use, subjective scoring scale [International Committee on Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF), Incontinence Quality of Life (I-QOL)] and complications at 1 month after surgery. Social continence was defined as 0 to 1 pad use per day. Successful treatment was defined as social continence. Treatment improvement was defined as no social continence, but 50% or more improvement of symptoms compared with that before surgery. Other conditions were defined as treatment failure.Results:All operations were successfully completed. After 1 to 11 months of follow-up, all patients achieved social continence. The patients' postoperative daily use of urinary pads ranged from 0 to 1 piece, with a mean of 0.5 piece. ICI-Q-SF scores ranged from 1 to 7, with a mean of 3. I-QOL scores ranged from 72.1 to 85.2, with a mean of 77.0. All the indicators were significantly improved compared with those before operation. In terms of postoperative complications, one patient had dysuria and urinary retention 2 days after the removal of the catheter, which was improved after symptomatic treatment of anti-inflammatory, detumescence, and indwelling catheter. At the last follow-up, there were no surgical related complications.Conclusions:The single-incision transobturator bulbourethral sling suspension without skin tunnel puncture for the treatment of male urinary incontinence is safe and effective. Compared to the traditional surgical method, it does not increase the difficulty of the procedure and is technically feasible, offering clinicians a new approach and perspective.
5.Effect and mechanism of berberine on proliferation and invasion of colon cancer cells
Shu ZHANG ; Shanshan MENG ; Yunhe ZHANG ; Jing CAI
Journal of Xinxiang Medical College 2024;41(11):1001-1007
Objective To explore the effect of berberine on the proliferation and invasion of human colon cancer cells and its mechanism.Methods The paraffin-embedded tumor tissues and intestinal incisal tissues(control tissues)of 96 patients who underwent radical resection of colon cancer at the First Affiliated Hospital of Henan University from January 2021 to December 2022 were selected as the research subjects.The expression of hypoxia-inducible factor-1α(HIF-1α)in tumor tissues and control tissues was detected by using the immunohistochemical method,and the relationship between HIF-1α and clinicopathological features was analyzed.The human colon cancer cell line HCT116 was cultivated in normoxic and hypoxic conditions,respectively;after adhesion,the cells were divided into normoxic group,hypoxic group,normoxic combined with berberine group,and hypoxic combined with berberine group.The cells in the normoxic combined with berberine group and the hypoxic combined with berberine group were treated with 25,50,75,and 100 μmol·L-1 berberine,respectively;while the cells in the normoxic group and the hypoxic group were not treated with any drugs.At 24,48,72,and 96 hours of cultivation,the proliferation of cells in each group was detected by using the thiazolyl blue tetrazolium bromide method,respectively.Based on the above results,the most suitable drug concentration was determined as 75 μmol·L-1.At 24 hours of cultivation,the invasion of cells in the normoxic group,normoxic combined with 75 μmol·L-1 berberine group,hypoxic group,and hypoxic combined with 75 μmol·L-1 berberine group was detected by using the Transwell method;at 48 hours of cultivation,the relative expression levels of HIF-1α and vascular endothelial growth factor(VEGF)proteins in the cells in each group were detected by using Western blot.Results HIF-1α was mainly expressed in the nucleus of colon cancer tissues and control tissues.The positive expression rates of HIF-1α in control tissues and colon cancer tissues were 19.8%(19/96)and 67.7%(65/96),respectively;the positive expression rate of HIF-1α in colon cancer tissues was significantly higher than that in control tissues(x2=11.298,P<0.05).The expression of HIF-1α in colon cancer tissues was correlated with tumor size,lymph node metastasis,and TNM staging(P<0.05),but had no correlation with patient gender,age,tumor infiltration depth,and differentiation degree(P>0.05).The cells in the normoxic group showed logarithmic growth after 24 hours of culture;and the addition of berberine at a concentration of 25 μmol·L-1 had no significant effect on cell proliferation(P>0.05);compared with 0 μmol·L-1berberine,the addition of berberine at concentrations of 50 μmol·L-1 and 75 μmol·L-1 significantly reduced cell proliferation activity after 48 hours of culture(P<0.05),and the addition of berberine at a concentration of 100 μmol·L-1 significantly reduced cell proliferation activity after 24 hours of culture(P<0.05).After 48 hours of culture with berberine at a concentration of 25 μmol·L-1,the proliferation activity of cells in the hypoxic group was significantly higher than that in the 0 μmol·L-1 berberine(P<0.05);compared with 0 μmol·L-1 berberine,the addition of berberine at concentrations of 50,75,and 100 μmol·L-1 significantly reduced cell proliferation activity after 24 hours of culture(P<0.05),and the higher the concentration of berberine,the more pronounced the decrease in cell proliferation activity(P<0.05).At the same concentration of berberine,compared with the normoxic group,the hypoxic group showed a more significant decrease in cell proliferation activity and a more pronounced slowing-down trend in cell proliferation(P<0.05).There was no statistically significant difference in the number of cells crossing the membrane between the normoxic group and the normoxic combined with 75 μmol·L-1 berberine group(t=0.955,P>0.05);the number of cells crossing the membrane in the hypoxic combined with 75 μmol·L-1 berberine group was significantly less than that in the hypoxic group(t=5.354,P<0.05);the number of cells crossing the membrane in the hypoxic group was significantly more than that in the normoxic group(t=2.625,P<0.05).There was no statistically significant difference in the relative expression levels of HIF-1α and VEGF proteins between the normoxic group and the normoxic combined with 75 μmol·L-1 berberine group(P>0.05);the relative expression levels of HIF-1α and VEGF proteins in the hypoxic group were significantly higher than those in the normoxic group(P<0.05);the relative expression levels of HIF-1α and VEGF proteins in the hypoxic combined with 75 μmol·L-1 berberine group were significantly lower than those in the hypoxic group(P<0.05);there was no statistically significant difference in the relative expression levels of HIF-1α and VEGF proteins between the normoxic combined with 75 μmol·L-1 berberine group and the hypoxic combined with 75 μmol·L-1 berberine group(P>0.05).Conclusion HIF-1α expression is associated with growth and invasion of colon cancer.Berberine may inhibit the proliferation and invasion of colon cancer cells HCT116 by regulating the expression of HIF-1α and its downstream factor VEGF.
6.Efficacy and safety of micropulse transscleral cyclophotocoagulation in the treatment of refractory glaucoma: a prospective multicenter observational study
Fengbin LIN ; Baiyu HU ; Qiying LING ; Yunhe SONG ; Xinbo GAO ; Yingzhe ZHANG ; Yu CHEN ; Xuanchu DUAN ; Liuzhi ZENG ; Xiulan ZHANG
Chinese Journal of Experimental Ophthalmology 2024;42(6):527-531
Objective:To evaluate the efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) for refractory glaucoma.Methods:A prospective multicenter observational case series study was conducted.A total of 63 refractory glaucoma patients (67 eyes) who underwent MP-TSCPC treatment were enrolled at Zhongshan Ophthalmic Center, Sun Yat-sen University, Chengdu First People's Hospital (Chengdu Integrated TCM& Western Medicine Hospital), and Changsha Aier Eye Hospital from August 2022 to April 2023.Among these cases, there were 40 eyes (59.7%) with unreduced intraocular pressure (IOP) after glaucoma surgery, 4 eyes (6.0%) with secondary glaucoma after vitrectomy, 2 eyes (3.0%) with secondary glaucoma after keratoplasty, 8 eyes (11.9%) with neovascular glaucoma, 3 eyes (4.5%) with secondary glaucoma due to iridocorneal endothelial syndrome, 6 eyes (9.0%) with primary open-angle glaucoma and 4 eyes (6.0%) with primary angle-closure glaucoma.Best corrected visual acuity (BCVA) was measured using the ETDRS chart and the IOP was measured using the Goldmann applanation tonometry before and 6 months after the surgery.The usage of anti-glaucoma medications before and after surgery and postoperative complications were recorded.Surgical success rate was calculated and surgical success was defined as an IOP reduction of more than 20% from baseline or a reduction in the number of ocular hypotensive medications with no change in IOP.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No.2022KYPJ225).Written informed consent was obtained from each subject.Results:There was a statistically significant overall difference in IOP at different time points before and after surgery ( F=60.10, P<0.001), and the IOP at different time points after surgery was significantly lower than that before surgery, with statistically significant differences (all at P<0.001).IOP reduction at 6 months after surgery was (43.7±20.7)%.The number of anti-glaucoma medications used postoperatively was 2(0, 3) types, which was significantly less than the 3(2, 3) types used preoperatively ( Z=-2.70, P=0.007).The 6-month postoperative BCVA (LogMAR) was 1.40(0.52, 2.70), which showed no significant change compared to the preoperative 1.40(0.70, 2.70) ( Z=-0.10, P=0.952).The surgical success rate was 83.6%(56/67) at 6 months postoperatively.Postoperative complications included mydriasis (11/67), conjunctival hemorrhage (11/67), mild anterior chamber inflammation (1/67), mild ciliary body detachment (3/67), local choroidal detachment (1/67), and cystoid macular edema (1/67), all of which were reversible after treatment. Conclusions:MP-TSCPC appears to be a safe and effective treatment option for refractory glaucoma.
7.Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones
Song QIANLIN ; Song CHAO ; Chen XIN ; Xiong YUNHE ; He ZIQI ; Su XIAOZHE ; Zhou JIAWEI ; Ke HU ; Dong CAITAO ; Liao WENBIAO ; Yang SIXING
Journal of Pharmaceutical Analysis 2024;14(6):851-862
Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.
8.Effects of indobuprofen combined with nicodil on inflammatory factors,myocardial injury markers and platelet function in patients with ACS after PCI
Shuhong RUI ; Chenfang WANG ; Yunhe LI ; Junlan PAN ; Jianlou WANG
The Journal of Practical Medicine 2024;40(12):1706-1711
Objective To investigate the efficacy of indobuprofen combined with nicodil for the treatment of acute coronary syndromes(ACS)and the effects of percutaneous coronary intervention on patients Effects of myocardial injury markers,platelet function and inflammatory factors after intervention(PCI).Method A total of 150 patients with ACS admitted to the hospital from January 2021 to December 2022 were divided into groups according to different treatment methods.The control group(n=75)was given nicodil combined with antiplatelet therapy,and the study group(n=75)was given indobufen combined with nicodil combined with antiplatelet therapy.Both groups were treated for 2 weeks.The clinical efficacy of the two groups was compared,the changes of myocardial injury markers,platelet function and inflammatory factors before and after treatment were monitored,and the total incidence of adverse reactions was recorded.Results The total effective rate of the group treated with nicodil combined with indobufen was 98.67%higher than that of the control group treated with nicodil alone,90.67%(χ2=4.754,P<0.05).The levels of myocardial injury markers such as cTnI and CK-MB in the study group after treatment were lower than those in the control group(t=15.492,3.250,P<0.05).The levels of platelet function indexes such as CD62p,CD63,GPⅡb/Ⅲa in the study group after treatment were lower than those in the control group(t=2.034,3.257,2.221,P<0.05).The levels of CRP,TNF-α,IL-6 and other inflammatory factors in the study group were lower than those in the control group after treatment(t=21.862,3.378,2.131,P<0.05).The total incidence of adverse reactions after treatment was 4.00%in the study group and 2.67%in the control group(P>0.05).Conclusion The efficacy of indobufien combined with nicodil in the treatment of ACS is better than that of nicodil alone,and it can improve myocardial injury and platelet function after PCI,inhibit the release of inflammatory factors,and the incidence of adverse reactions is lower.
9.Research progress on immune checkpoint inhibitors for the treatment of adverse reactions related to gastric cancer
Yawen CHEN ; Yunhe GAO ; Zhi QIAO
International Journal of Surgery 2024;51(1):54-60
Traditional chemotherapy is the cornerstone of comprehensive treatment for gastric cancer, but its recurrence and metastasis rates are high, and the overall prognosis is not ideal. The rise of immune checkpoint inhibitors (ICI) has brought new hope to gastric cancer patients and changed the current pattern of comprehensive treatment for gastric cancer. With the increasing use of ICI, immune related adverse reactions (irAEs) such as skin toxicity and gastrointestinal toxicity are becoming increasingly common. Scientific understanding, early diagnosis, and graded management are currently the main strategies for handling irAEs. This article aims to review the mechanisms, clinical manifestations, and prediction, treatment, and management of irAEs after ICI treatment of gastric cancer, in order to enhance the understanding of irAEs among clinical physicians, better manage immunotherapy related adverse reactions, and improve the prognosis and quality of life of patients.
10.Prognosis and influencing factors analysis of patients with initially resectable gastric cancer liver metastasis who were treated by different modalities: a nationwide, multicenter clinical study
Li LI ; Yunhe GAO ; Liang SHANG ; Zhaoqing TANG ; Kan XUE ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Bin KE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Hongqing XI ; Yun TANG ; Zhi QIAO ; Han LIANG ; Jiafu JI ; Lin CHEN
Chinese Journal of Digestive Surgery 2024;23(1):114-124
Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

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