Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Objective:To investigate the effect of glucagon like peptide-2(GLP-2)on 2,4,6-trinitrobenzenesulfonic acid(TNBS)induced intestinal mucosal tissue damage and the effects of helper T cell 1/helper T cell 2(Th1/Th2)balance in rats with Crohn's disease(CD).Methods:Forty rats were randomly divided into control group,CD group,treatment(CD+GLP-2)group and positive control[CD+sulfasalazine(SASP)]group,with 10 rats in each group.TNBS induced CD model was established and the rats in the other 3 groups were given corresponding treatment.After completion,colon macroscopic damage index(CMDI)was evaluated,HE staining was used to observe the histopathological changes of intestinal mucosa,TUNEL staining was used to detect apoptosis of co-lonic tissue cells,ELISA was used to determine serum IFN-γ,TNF-α,IL-12,IL-4 and IL-10,immunohistochemical staining was used to detect the expressions of IFN-γ and IL-4 in colon tissues,flow cytometry was used to determine the proportion of Th1/Th2 in spleen.Results:Compared with CD group,CMDI in CD+GLP-2 group and CD+SASP group were significantly decreased(P all<0.001),intes-tinal mucosal damage was improved,the positive rate of TUNEL in colon tissue was significantly decreased(P all<0.001),the con-tents of IFN-γ,TNF-α and IL-12 in serum were significantly decreased(P all<0.001),the contents of IL-4 and IL-10 in serum were significantly increased(P all<0.001),the expression of IFN-γ in colon tissue was significantly decreased and the expression of IL-4 was significantly increased(P all<0.001),the proportion of Th1 cells was significantly decreased while the proportion of Th2 cells was significantly increased(P all<0.001),Th1/Th2 also decreased significantly(P all<0.001).Conclusion:GLP-2 can effectively im-prove the intestinal mucosal injury of CD rats induced by TNBS,and the mechanism may be related to regulating the immune balance of Th1/Th2 cells,inhibiting inflammatory response and reducing cell apoptosis.

Natural polyphenols are a group of components widely found in traditional Chinese medicines and have been demonstrated to delay or prevent the development of aging and age-related diseases in recent years. As far as we know, the studies of natural polyphenols in aging and aging-related diseases have never been extensively reviewed. In the present paper, we reviewed recent advances of natural polyphenols in aging and common age-related diseases and the current technological methods to improve the bioavailability of natural polyphenols. The results showed that natural polyphenols have the potential to prevent or treat aging and common age-related diseases through multiple mechanisms. Nanotechnology, structural modifications, and matrix processing could provide strong technical support for the development of natural polyphenols to prevent or treat aging and age-related diseases. In conclusion, natural polyphenols have important potential in the prevention and treatment of aging and age-related diseases.

Objective To explore the protective effect and mechanism of Xinkang Granules-containing serum in adriamycin-induced injury of cardiomyocytes H9C2 based on cGAS-STING signaling axis.Methods Adriamycin was used to induce the H9C2 cells injury model.The cells were divided into normal group,model group,Xinkang Granules group and inhibitor group.After 24 hours of intervention,the CCK-8 method was used to detect cell survival rate,the DCFH-DA fluorescent probe was used to detect the content of cell reactive oxygen species(ROS),cell apoptosis rate was detected by flow cytometry,ELISA was used to detect the content of tumor necrosis factor-α(TNF-α)in cell supernatant,colorimetry was used to detect lactate dehydrogenase(LDH)in cells,RT-qPCR was used to detect the expression of mitochondrial transcription factor A(TFAM),cyclic guanosine-adenylate synthetase(cGAS),stimulator of interferon genes(STING)and TNF-α mRNA,Western blot and immunofluorescence were used to detect the protein expressions of cGAS and STING.Results Compared with the normal group,cell survival rate in the model group was significantly reduced(P<0.01),the ROS content was significantly increased(P<0.01),the apoptosis rate significantly increased(P<0.01),the content of TNF-α in the supernatant significantly increased(P<0.01),the activity of LDH significantly increased(P<0.01),the expression of TFAM mRNA significantly decreased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expression of cGAS and STING significantly increased(P<0.01).Compared with the model group,cell survival rate in Xinkang Granules group and inhibitor group significantly increased(P<0.01),the ROS content significantly decreased(P<0.01),the apoptosis rate significantly decreased(P<0.01),the content of TNF-α in supernatant significantly decreased(P<0.01),the activity of LDH significantly decreased(P<0.01),the expression of TFAM mRNA significantly increased(P<0.01),and the expressions of TNF-α,cGAS,STING mRNA and the protein expressions of cGAS and STING significantly decreased(P<0.05,P<0.01).Conclusion Xinkang Granules have a protective effect on adriamycin-induced H9C2 cardiomyocytes,which may be related to the inhibition of cGAS/STING axis activation and the secretion of inflammatory factors.

Objective:To investigate the effect of glucagon like peptide-2(GLP-2)on 2,4,6-trinitrobenzenesulfonic acid(TNBS)induced intestinal mucosal tissue damage and the effects of helper T cell 1/helper T cell 2(Th1/Th2)balance in rats with Crohn's disease(CD).Methods:Forty rats were randomly divided into control group,CD group,treatment(CD+GLP-2)group and positive control[CD+sulfasalazine(SASP)]group,with 10 rats in each group.TNBS induced CD model was established and the rats in the other 3 groups were given corresponding treatment.After completion,colon macroscopic damage index(CMDI)was evaluated,HE staining was used to observe the histopathological changes of intestinal mucosa,TUNEL staining was used to detect apoptosis of co-lonic tissue cells,ELISA was used to determine serum IFN-γ,TNF-α,IL-12,IL-4 and IL-10,immunohistochemical staining was used to detect the expressions of IFN-γ and IL-4 in colon tissues,flow cytometry was used to determine the proportion of Th1/Th2 in spleen.Results:Compared with CD group,CMDI in CD+GLP-2 group and CD+SASP group were significantly decreased(P all<0.001),intes-tinal mucosal damage was improved,the positive rate of TUNEL in colon tissue was significantly decreased(P all<0.001),the con-tents of IFN-γ,TNF-α and IL-12 in serum were significantly decreased(P all<0.001),the contents of IL-4 and IL-10 in serum were significantly increased(P all<0.001),the expression of IFN-γ in colon tissue was significantly decreased and the expression of IL-4 was significantly increased(P all<0.001),the proportion of Th1 cells was significantly decreased while the proportion of Th2 cells was significantly increased(P all<0.001),Th1/Th2 also decreased significantly(P all<0.001).Conclusion:GLP-2 can effectively im-prove the intestinal mucosal injury of CD rats induced by TNBS,and the mechanism may be related to regulating the immune balance of Th1/Th2 cells,inhibiting inflammatory response and reducing cell apoptosis.

BACKGROUND:Intra-articular injection played an important role in the treatment of osteoarthritis and has more options with the development of novel drug delivery systems.The cartilage targeting function is aimed at the adhesion or retention of drugs in the cartilage layer to form a drug bank to achieve slow release and precise drug delivery. OBJECTIVE:To review various cartilage targeting biomaterials and their characteristics in the treatment of osteoarthritis by articular injection. METHODS:Using the term"osteoarthritis,drug carrier,drug delivery,cartilage targeting,penetrate"as key words,relevant articles were searched in CNKI,WanFang and PubMed databases.According to inclusion and exclusion criteria,67 articles were finally selected for further review. RESULTS AND CONCLUSION:The research on cartilage-targeting biomaterials is mainly divided into two directions.One is the combination of electrostatic interaction,such as the combination of positively charged biomaterials and negatively charged polysaccharides in cartilage.This kind of scheme is operable and easy to modify,but limited by the shortcomings of electrostatic interaction itself,it performs badly in advanced osteoarthritis.Another one is the specific binding of various components in cartilage which is strong and reliable,and related biomaterials have excellent performance in advanced osteoarthritis,which is an important direction for future cartilage-targeted therapy.

Objective To explore the intervention effect and molecular mechanism of Xinkang Granules on inflammatory factors in rats with chronic heart failure based on cGAS/STING signaling pathway.Methods SD rats were randomly divided into normal group and modeling group.The chronic heart failure model was established by intraperitoneal injection of Doxorubicin Hydrochloride.After successfully modeling,the rats were further divided into model group,Valsartan group and Xinkang Granules group.The model group was treated with distilled water every day,the Valsartan group was treated with Valsartan solution every day,and the Xinkang Granules group was treated with Xinkang Granules every day,all given for 4 consecutive weeks.Echocardiography was used to detect cardiac function,the pathological changes of myocardium were detected by hematoxylin-eosin staining(HE),the ultrastructural changes of myocardium in each group were observed by transmission electron microscope,and the contents of interleukin-1β(IL-1β)and interleukin-6(IL-6)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of mitochondrial transcription factor A(TFAM),cyclic guanosine monophosphate-adenylate synthase(cGAS),interferon-stimulated gene(STING)and IL-6 in myocardial tissue of rats in each group were detected by real-time fluorescence quantitative method(qPCR).The protein expressions of cGAS and STING in rat myocardial tissue were detected by immunohistochemical method.Results Compared with the blank group,the rats in the model group had significant inflammatory cell infiltration and inflammatory edema in myocardial tissue,their cardiac function was significantly reduced(P＜0.05,P＜0.01),and serum inflammatory factors were significantly increased(P＜0.01).The mRNA expression of TFAM in myocardial tissue was significantly reduced(P＜0.01),the mRNA expressions of IL-6,cGAS,and STING were significantly increased(P＜0.01),and the protein expressions of cGAS and STING in the myocardial tissue were significantly increased(P＜0.01).Compared with the model group,the cardiac function of the rats in the Xinkang Granules group was significantly improved(P＜0.05,P＜0.01),the inflammatory infiltration of myocardial cells was reduced,the expression of serum inflammatory factors was significantly reduced(P＜0.01),the mRNA expression of TFAM in myocardial tissue was significantly increased(P＜0.05),and the mRNA expressions of IL-6,cGAS,and STING were significantly decreased(P＜0.01),the protein expressions of cGAS and STING in myocardial tissue were significantly decreased(P＜0.01).Conclusion Xinkang Granules can reduce the expression of inflammatory factors and improve cardiac function in rats with chronic heart failure.Its mechanism may be related to inhibiting the cGAS/STING signaling pathway.

OBJECTIVE: To investigate the chemical constituents from the leaves of Jatropha curcas and evaluate their inhibition on lipopolysaccharide (LPS)-activated BV-2 microglia cells. METHODS: The n-BuOH extract of the leaves of J. curcas was isolated by macroporous adsorption resin, silica gel, ODS, column chromatography and semi-preparative HPLC. The structures of the compounds were identified by MS, NMR, ECD, and other spectroscopic methods. In addition, anti-neuroinflammatory effects of isolated compounds were evaluated by measuring the production of nitric oxide (NO) in over-activated BV-2 cells. RESULTS: Seventeen compounds, including (7R,8S)-crataegifin A-4-O-β-D-glucopyranoside ( 1), (8R,8'R)-arctigenin ( 2), arctigenin-4'-O-β-D-glucopyranoside ( 3), (-)-syringaresinol ( 4), syringaresinol-4'-O-β-D-glucopyranoside ( 5), (-)-pinoresinol ( 6), pinoresinol-4'-O-β-D-glucopyranoside ( 7), buddlenol D ( 8), (2R,3R)-dihydroquercetin ( 9), (2S,3S)-epicatechin ( 10), (2R,3S)-catechin ( 11), isovitexin ( 12), naringenin-7-O-β-D-glucopyranoside ( 13), chamaejasmin ( 14), neochamaejasmin B ( 15), isoneochamaejasmin A ( 16), and tomentin-5-O-β-D-glucopyranoside ( 17) were isolated and identified. Compounds 2, 4 and 8 significantly inhibited the release of NO in BV-2 microglia activated by LPS, with IC₅₀ values of 18.34, 29.33 and 26.30 μmol/L, respectively. CONCLUSION Compound 1 is a novel compound, and compounds 2, 3, 8, 14- 17 are isolated from Jatropha genus for the first time. In addition, the lignans significantly inhibited NO release and the inhibitory activity was decreased after glycosylation.

Objective:To investigate the application value of intrathoracic double-flap tech-nique (Kamikawa anastomosis) in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 10 patients with esophagogastric junction cancer who were admitted to the First Affiliated Hospital of Xiamen University between July 2022 and April 2023 were collec-ted. There were 7 males and 3 females, aged 62(range, 53-71)years. All the 10 patients underwent combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer. Reconstruction was performed with an intrathoracic Kamikawa anastomosis. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3) follow-up and survival. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Intraoperative and postoperative situations. All the 10 patients underwent surgery successfully. The operation time and volume of intraoperative blood loss were (347±41)minutes and (91±41)mL. The time to postoperative fluid diet intake, time to removal of postoperative abdominal drainage tube, time to removal of postoperative chest drainage tube, duration of postoperative hospital stay were (4.3±1.1)days, (5.0±1.6)days, (10.5±3.9)days, (13.3±3.8)days. Six patients had postoperative complications, including 1 case of Clavien-Dindo grade ⅢB, 3 cases of Clavien Dindo grade Ⅱ, 2 cases of Clavien Dindo grade Ⅰ. An upper gastrointestinal contrast at postoperative day 7 showed no anastomotic leak or anastomotic stricture in the 10 patients. (2) Postoperative pathological examination. Results of postoperative pathological examination in the 10 patients showed negative surgical margin. The number of lymph node dissected was 22±6. There were 3 patients with 5 positive lymph nodes. The tumor diameter and distance from center of tumor to squamocolumnar mucosal junction were (3.3±0.5)cm and (1.9±1.4)cm. One patient had tumor differentiation degree as high and moderate differentiation, 5 cases as moderate differentiation, 3 cases as moderate and low differentiation, 1 case as low differentiation. There were 5 patients with squamous cell carcinoma of the esophagogastric junction and 5 patients with adenocarcinoma of the esophagogastric junction. (3) Follow-up and survival. All the 10 patients were followed up for 7(range, 3?12)months, achieving disease-free survival. The visick quality of life grade Ⅰ, Ⅱ, Ⅲ, Ⅳ were observed in 7, 3, 0, 0 patients. Postoperative gastroscopy was completed in 7 patients, in which mild anastomotic strictures were noted in 2 patients, but no treatment was required. There was no reflux esophagitis.Conclusion:Intrathoracic Kamikawa anastomosis in combined thoracoscopic and laparoscopic radical resection for esophagogastric junction cancer is safe and feasible, with satisfactory short-term efficacy.

Objective:To investigate the application value of transanal endoscopic partial intersphincteric resection for ultra-low rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 9 ultra-low rectal cancer patients undergoing transanal endoscopic partial intersphincteric resection at the First Affiliated Hospital of Xiamen University from December 2017 to August 2020 were collected. There were 8 males and 1 female, aged from 39 to 62 years, with a median age of 58 years. Observation indicators: (1) surgical and postoperative situations; (2) postoperative pathological examination; (3) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect postoperative tumor local recurrence and distant metastasis, survival of patients, ileostomy closure, anus function at 3 months after ileostomy closure, male urinary and sexual function and female sexual function at 6 months after rectal surgery. The follow-up was up to February 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1)Surgical and postoperative situations: all 9 patients underwent surgery successfully, without conversion to open surgery. Seven of the 9 patients underwent transanal endoscopic partial intersphincteric resection and the rest of 2 patients with tumor close to the dentate line underwent transanal endoscopic modified partial intersphincteric resection. The operation time and volume of intraoperative blood loss of 9 patients were (267±48)minutes and 50 mL(range, 30?60 mL), respectively. Five of the 9 patients underwent transanal specimen extraction, and 4 patients underwent specimen extraction by an abdominal incision. All 9 patients underwent transanal hand-sewn coloanal anastomosis and protective ileostomy, and two pelvic drainage tubes were indwelled. Transanal drainage tube was placed after anastomosis in 3 of 9 patients. Three cases had intraoperative adverse events and there were no intraoperative adverse event reported in the remaining 6 cases. The time to postoperative initial stoma exhausting and time to postoperative first semi-liquid food intake of 9 patients were 3 days(range, 2?4 days) and 5 days(range, 4?7 days), respectively. One case had Clavien-Dindo grade Ⅰ complication and 2 cases had Clavien-Dindo grade Ⅱ complication during postoperative 30 days and the rest of 6 cases had no postoperative complication. No anastomotic stricture, hemorrhage or urinary retention occurred in 9 patients. The duration of postoperative hospital stay and cost of hospitalization of 9 patients were 11 days(range, 9?23 days) and (6.8±1.3)×10 4 yuan, respectively. (2) Postoperative pathological examination: the diameter of tumor, the distance of distal resection margin, the number of lymph node dissected and the number of positive lymph node of 9 patients were (3.2±1.4)cm, 0.6 cm(range, 0.5?1.5 cm), 17±7 and 0(range, 0?7), respectively. The tumor histopathological type was adenocarcinoma with negative tumor nodule and nerve infiltration in all 9 patients. Only 1 case of 9 patients was found vascular tumor thrombus. The surgical specimens of all 9 patients showed negative for distal and circumferential margins and complete mesorectum. Results of postoperative pathological TNM staging showed that of 6 cases with preoperative T1-T2 staging tumors, 3 cases were classified as pT2N0M0 stage, and 3 cases were classified as pT2N1M0 stage, pT2N2M0 stage or pT3N1M0 stage, respectively. Three cases with preoperative T3 staging tumors were classified as ypT0N0M0 stage, ypT2N0M0 stage or ypT3N0M0 stage, respectively. (3) Follow-up: all 9 patients were followed up for 6 to 13 months, with a median follow-up time of 9 months. No local recurrence, distant metastasis or tumor-related death was found during follow-up. Of the 9 patients, only 1 case did not receive stoma closure and undergo anus function assessment, and the rest of 8 cases underwent stoma closure. Results of postoperative anus function assessment showed 5 cases of accessibility, 2 cases of mild impairment and 1 case of severe impairment. Results of urogenital function assessment showed 6 cases of the 8 male patients of mild impairment, 1 case of moderate impairment and 1 case of severe impairment in micturition function, respectively, and 3 cases of accessibility, 2 cases of mild impairment and 3 cases of moderate impairment in sexual function, respectively. The female patient underwent accessibility of sexual function and the six-item version of the female sexual function index was 25. Conclusion:Transanal endoscopic partial intersphincteric resection can be used for the treatment of ultra-low rectal cancer.