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.

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.

In recent years, advances in surgical techniques and evolving concepts have significantly improved treatment strategies and prognosis for patients with gastric cancer liver metastases. In particular, patients diagnosed with initially resectable gastric cancer liver metastases shows marked improvement in survival. Despite variations in the definition of initially resectable gastric cancer liver metastases among different consensus and guidelines, surgical resection and hepatic physiotherapy are increasingly crucial components of comprehensive treatment. Meanwhile, the advancement of the multidisciplinary team model for diagnosis and treatment, along with the evolution of minimally invasive surgical concepts, offers patients increasingly personalized and less intrusive therapeutic alternatives. According to the Chinese Consensus Classification System for Gastric Cancer Liver Metastasis, the optimal clinical pathway for patients initially diagnosed with resectable gastric cancer liver metastasis involves precise categorization, guided selection of surgical approaches and physiotherapy using the multidisciplinary team model, and consideration of molecular classification. However, the refinement and confirmation of these clinical strategies is still required through high-quality clinical trials.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To investigate the prevalence and risk factors of sarcopenia in patients following radical gastrectomy with the aim of guiding clinical decisions.Methods:This was a retrospective observational study of data of patients who had undergone radical gastrectomy between June 2021 and June 2022 at the Department of General Surgery, First Medical Center of Chinese PLA General Hospital. Participants were reviewed 9-12 months after surgery. Inclusion criteria were as follows: (1) radical gastrectomy with a postoperative pathological diagnosis of primary gastric cancer; (2) no invasion of neighboring organs, peritoneal dissemination, or distant metastasis confirmed intra- or postoperatively; (3) availability of complete clinical data, including abdominal enhanced computed tomography and pertinent blood laboratory tests 9-12 after surgery. Exclusion criteria were as follows: (1) age <18 years; (2) presence of gastric stump cancer or previous gastrectomy; (3) history of or current other primary tumors within the past 5 years; (4) preoperative diagnosis of sarcopenia (skeletal muscle index [SMI) ≤52.4 cm2/m2 for men, SMI ≤38.5 cm2/m2 for women). The primary focus of the study was to investigate development of postoperative sarcopenia in the study cohort. Univariate and multivariate logistic regression were used to identify the factors associated with development of sarcopenia after radical gastrectomy.Results:The study cohort comprised 373 patients of average age of 57.1±12.3 years, comprising 292 (78.3%) men and 81 (21.7%) women. Postoperative sarcopenia was detected in 81 (21.7%) patients in the entire cohort. The SMI for the entire group was (41.79±7.70) cm 2/m 2: (46.40±5.03) cm 2/m 2 for men and (33.52±3.63) cm 2/m 2 for women. According to multivariate logistic regression analysis, age ≥60 years (OR=2.170, 95%CI: 1.175-4.007, P=0.013), high literacy (OR=2.512, 95%CI: 1.238-5.093, P=0.011), poor exercise habits (OR=3.263, 95%CI: 1.648-6.458, P=0.001), development of hypoproteinemia (OR=2.312, 95%CI: 1.088–4.913, P=0.029), development of hypertension (OR=2.169, 95%CI: 1.180-3.984, P=0.013), and total gastrectomy (OR=2.444, 95%CI:1.214-4.013, P=0.012) were independent risk factors for postoperative sarcopenia in post-gastrectomy patients who had had gastric cancer ( P<0.05). Conclusion:Development of sarcopenia following radical gastrectomy demands attention. Older age, higher education, poor exercise habits, hypoproteinemia, hypertension, and total gastrectomy are risk factors for its development post-radical gastrectomy.

Objective:To investigate the prevalence and risk factors of sarcopenia in patients following radical gastrectomy with the aim of guiding clinical decisions.Methods:This was a retrospective observational study of data of patients who had undergone radical gastrectomy between June 2021 and June 2022 at the Department of General Surgery, First Medical Center of Chinese PLA General Hospital. Participants were reviewed 9-12 months after surgery. Inclusion criteria were as follows: (1) radical gastrectomy with a postoperative pathological diagnosis of primary gastric cancer; (2) no invasion of neighboring organs, peritoneal dissemination, or distant metastasis confirmed intra- or postoperatively; (3) availability of complete clinical data, including abdominal enhanced computed tomography and pertinent blood laboratory tests 9-12 after surgery. Exclusion criteria were as follows: (1) age <18 years; (2) presence of gastric stump cancer or previous gastrectomy; (3) history of or current other primary tumors within the past 5 years; (4) preoperative diagnosis of sarcopenia (skeletal muscle index [SMI) ≤52.4 cm2/m2 for men, SMI ≤38.5 cm2/m2 for women). The primary focus of the study was to investigate development of postoperative sarcopenia in the study cohort. Univariate and multivariate logistic regression were used to identify the factors associated with development of sarcopenia after radical gastrectomy.Results:The study cohort comprised 373 patients of average age of 57.1±12.3 years, comprising 292 (78.3%) men and 81 (21.7%) women. Postoperative sarcopenia was detected in 81 (21.7%) patients in the entire cohort. The SMI for the entire group was (41.79±7.70) cm 2/m 2: (46.40±5.03) cm 2/m 2 for men and (33.52±3.63) cm 2/m 2 for women. According to multivariate logistic regression analysis, age ≥60 years (OR=2.170, 95%CI: 1.175-4.007, P=0.013), high literacy (OR=2.512, 95%CI: 1.238-5.093, P=0.011), poor exercise habits (OR=3.263, 95%CI: 1.648-6.458, P=0.001), development of hypoproteinemia (OR=2.312, 95%CI: 1.088–4.913, P=0.029), development of hypertension (OR=2.169, 95%CI: 1.180-3.984, P=0.013), and total gastrectomy (OR=2.444, 95%CI:1.214-4.013, P=0.012) were independent risk factors for postoperative sarcopenia in post-gastrectomy patients who had had gastric cancer ( P<0.05). Conclusion:Development of sarcopenia following radical gastrectomy demands attention. Older age, higher education, poor exercise habits, hypoproteinemia, hypertension, and total gastrectomy are risk factors for its development post-radical gastrectomy.

In recent years, advances in surgical techniques and evolving concepts have significantly improved treatment strategies and prognosis for patients with gastric cancer liver metastases. In particular, patients diagnosed with initially resectable gastric cancer liver metastases shows marked improvement in survival. Despite variations in the definition of initially resectable gastric cancer liver metastases among different consensus and guidelines, surgical resection and hepatic physiotherapy are increasingly crucial components of comprehensive treatment. Meanwhile, the advancement of the multidisciplinary team model for diagnosis and treatment, along with the evolution of minimally invasive surgical concepts, offers patients increasingly personalized and less intrusive therapeutic alternatives. According to the Chinese Consensus Classification System for Gastric Cancer Liver Metastasis, the optimal clinical pathway for patients initially diagnosed with resectable gastric cancer liver metastasis involves precise categorization, guided selection of surgical approaches and physiotherapy using the multidisciplinary team model, and consideration of molecular classification. However, the refinement and confirmation of these clinical strategies is still required through high-quality clinical trials.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

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.

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.