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.Prevalence and risk factors of sarcopenia after radical gastrectomy for gastric cancer
Jing ZHOU ; Xuefen CHEN ; Yunhe GAO ; Fei YAN ; Hongqing XI
Chinese Journal of Gastrointestinal Surgery 2024;27(2):189-195
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.
4.Progress and implementing of novel surgical concepts and techniques in patients with resectable gastric cancer liver metastasis
Chinese Journal of Surgery 2024;62(5):359-363
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.
5.Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases
Li LI ; Yunhe GAO ; Lu ZANG ; Kan XUE ; Bin KE ; Liang SHANG ; Zhaoqing TANG ; Jiang YU ; Yanrui LIANG ; Zirui HE ; Hualong ZHENG ; Hua HUANG ; Jianping XIONG ; Zhongyuan HE ; Jiyang LI ; Tingting LU ; Qiying SONG ; Shihe LIU ; Yawen CHEN ; Yun TANG ; Han LIANG ; Zhi QIAO ; Lin CHEN
Chinese Journal of Surgery 2024;62(5):370-378
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.
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.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.
10.Progress and implementing of novel surgical concepts and techniques in patients with resectable gastric cancer liver metastasis
Chinese Journal of Surgery 2024;62(5):359-363
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.

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