ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Objective To investigate the correlation between the expression of circulating exosome miR-485-3p and STYX with the risk of premature coronary heart disease.Methods A total of 50 inpatients with early onset coronary heart disease diagnosed by coronary angiography or CT angiography (CTA) in Af-filiated Puyang Municipal People's Hospital of Xinxiang Medical College from August to December 2023 were selected as the study group and 50 patients with excluded coronary artery disease by examination during the same period were included in the control group.The general clinical data of the two groups were collected,the plasma exosome miR-485-3p and STYX levels were detected.The degree of coronary arterial lesions in the pa-tients of the study group was evaluated by the Gensini score.The Spearman correlation analysis was used to analyze the relationship between plasma exosome miR-485-3p and STYX with LDL and Gensini score.The re-ceiver operating characteristic (ROC) curve was used to analyze the diagnostic value of plasma exosome miR-485-3p and STYX in the diagnosis of premature coronary heart disease.The multivariate logistic regression was used to determine the independent risk factors for premature coronary heart disease.Results Compared with the control group,the family history of coronary heart disease,smoking history,LDL and plasma exo-some miR-485-3p level in the study group were increased,the plasma STYX level was decreased and the differences were statistically significant (P<0.05);the Spearman correlation analysis showed that miR-485-3p was positively correlated with LDL (r=0.546) and Gensini score (r=0.485),and negatively correlated with STYX (r=-0.576).STYX was negatively correlated with LDL (r=-0.389) and Gensini score (r=-0.531).The ROC curve showed that the area under the curve of miR-485-3p,STYX and their combination in the diagnosis of premature coronary heart disease was 0.821 (95％CI:0.736-0.906),0.850 (95％CI:0.772-0.927) and 0.899 (95％CI:0.837-0.960) respectively.Conclusion The expression of circulating exosome miR-485-3p in premature coronary heart disease is up-regulated and the expression of STYX is down-regulated,the both are closely related to the degree of coronary artery lesion,which could be used as the po-tential biomarkers for the diagnosis of premature coronary heart disease.

Objective: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. Methods: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. Results: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). Conclusions and Relevance: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

ObjectiveTo observe the effects of the water extract of modified Xiao Xianxiongtang on microenvironment of gastric cancer MGC-803 cells， and to explore its possible mechanism in inhibiting the invasion and metastasis and epithelial-mesenchymal transformation （EMT） of MGC-803 cells and regulating Wnt5a/Ca²⁺/nuclear factor of activated T-cells （NFAT） signaling pathway by regulating microenvironment. MethodThe model of MGC-803 cells was established by transforming growth factor-β₁ （TGF-β₁）. The MGC-803 cells were divided into blank group， model group， and modified Xiao Xianxiongtang （10， 20， 40 mg·L^-1） groups. After transfection of Wnt5a overexpression plasmid， they were divided into pEX-normal control （NC） group， pEX-Wnt5a group， pEX-NC+modified Xiao Xianxiongtang （40 mg·L^-1） group and pEX-Wnt5a+modified Xiao Xianxiongtang （40 mg·L^-1） group. The invasion ability， migration ability， key factors of microenvironment， epithelial mesenchymal transformation （EMT） gene， Wnt5a， calcineurin （CaN）， NFAT1， phosphorylated （p）-NFAT1 and NFAT1 nuclear protein expression and cell Ca²⁺ concentration of MGC-803 cells were observed. ResultCompared with the blank group， the microenvironment in the model group was significantly up-regulated（P<0.01）， and compared with the model group， modified Xiao Xianxiongtang （10，20， 40 mg·L^-1） could significantly inhibit the microenvironment（P<0.05， P<0.01）. Further experiments showed that compared with the blank group， the number of invasive cells increased， the scratch rate increased， the microenvironmental factors and EMT gene were activated and the Wnt5a/Ca²⁺/NFAT pathway was activated in the model group after overexpression of Wnt5a. Compared with the model group， modified Xiao Xianxiongtang could inhibit cell distant invasion and reduce healing， inhibit microenvironment， EMT development， and Wnt5a/Ca²⁺/NFAT signal transduction， reduce NFAT1 nuclear expression and NFAT1-mediated transcriptional activity， thus reduce cell Ca²⁺ concentration， and reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionModified Xiao Xianxiongtang could regulate Wnt5a/Ca²⁺/NFAT pathway and inhibit the invasion and metastasis of gastric cancer and EMT progression by improving tumor microenvironment.

Blunt bowel injury (BBI) is relatively rare but life-threatening when delayed in surgical repair or anastomosis. Providing enteral nutrition (EN) in BBI patients with open abdomen after damage control surgery is challenging, especially for those with discontinuity of the bowel. Here, we report a 47-year-old male driver who was involved in a motor vehicle collision and developed ascites on post-trauma day 3. Emergency exploratory laparotomy at a local hospital revealed a complete rupture of the jejunum and then primary anastomosis was performed. Postoperatively, the patient was transferred to our trauma center for septic shock and hyperbilirubinemia. Following salvage resuscitation, damage control laparotomy with open abdomen was performed for abdominal sepsis, and a temporary double enterostomy (TDE) was created where the anastomosis was ruptured. Given the TDE and high risk of malnutrition, multiple portions EN were performed, including a proximal portion EN support through a nasogastric tube and a distal portion EN via a jejunal feeding tube. Besides, chyme delivered from the proximal portion of TDE was injected into the distal portion of TDE via a jejunal feeding tube. Hyperbilirubinemia was alleviated with the increase in chyme reinfusion. After 6 months of home EN and chyme reinfusion, the patient finally underwent TDE reversal and abdominal wall reconstruction and was discharged with a regular diet. For BBI patients with postoperative hyperbilirubinemia who underwent open abdomen, the combination of multiple portions EN and chyme reinfusion may be a feasible and safe option.
Male ; Humans ; Middle Aged ; Enteral Nutrition ; Intestines/surgery* ; Intestinal Diseases ; Abdomen/surgery* ; Anastomosis, Surgical ; Abdominal Injuries/surgery*

ObjectiveTo evaluate the efficacy and safety of Linggui Zhugantang in the treatment of heart failure. MethodCNKI，Wanfang Data，VIP，CBM，PubMed，ClinicalKey，Cochrane Library ，Web of Science ，Medline and Embase were systematically searched to screen randomized controlled trials（RCT）of Linggui Zhugantang in the treatment of heart failure. Meta-analysis was performed on the included studies using RevMan 5.3 ResultTwenty-seven studies were included with a total sample size of 3 569 cases，including 1 816 in experimental group and 1 753 in control group. Meta-analysis showed that compared with conventional drugs alone，combination of Linggui Zhugantang and conventional drugs improved the marked effective rate [relative risk（RR）=1.41，95% confidence interval（CI）[1.29，1.54]，P<0.000 01] and the total effective rate（RR=1.21，95%CI[1.17，1.25]，P<0.000 01），decreased the levels of serum B-type brain natriuretic peptide （BNP）[mean difference（MD）=-390.08，95%CI[-538.84，-241.52]，P<0.000 01] and serum N-terminal pro-brain natriuretic peptide（NT-proBNP）（MD=-713.83，95%CI[-828.41, -599.25]，P<0.000 01）， left ventricular end-diastolic diameter（LVDD）（MD=-5.23，95%CI[-7.18, -3.29]，P<0.000 01）, left ventricular end-systolic diameter（LVSD）（MD=-4.54，95%CI[-6.75，-2.33]，P<0.000 01）, tumor necrosis factor-α（TNF-α）（MD=-37.53，95%CI [-50.72，-24.34]，P<0.000 01）and interleukin-6（IL-6）（MD=-23.64，95%CI [-47.40，0.11]，P=0.05）, increased left ventricular ejection fraction（LVEF）（MD=5.73，95%CI [3.33，8.14]，P<0.000 01），and cardiac output [stroke volume (SV) ]（MD=5.90，95%CI[4.56，7.25]，P<0.000 01）. In addition, the combination prolonged the 6 minute walking test distance（MD=51.08，95%CI [33.01，69.16]，P<0.000 01），reduced the traditional Chinese medicine (TCM) syndrome score（MD=-3.50，95%CI [-4.92，-2.07]，P<0.000 01），and improved quality of life（MD=-7.26，95%CI [-10.43，-4.09]，P<0.000 01），with higher safety（RR=0.36，95%CI [0.17，0.79]，P=0.01）. ConclusionLinggui Zhugantang combined with conventional drug therapy could improve cardiac function，reduce cardiac fibrosis，and improve prognosis, with high safety.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

The disease treatment of patients with gastrointestinal cancer is accompanied by impaired bodily functions. Frailty is very common in patients with gastrointestinal cancer, and is closely related to its various adverse health outcomes, which seriously affects their prognosis. This article reviews the risk factors, correlation with adverse health outcomes and intervention methods of frailty in gastrointestinal cancer patients. It is pointed out that medical and nursing staff should identify the frailty state of patients with gastrointestinal cancer as soon as possible and make early interventions to improve the prognosis of patients.

Objective:To conduct a bibliometric and visual analysis of the current status and trends of international research on keloids.Methods:The articles on keloid research from 2000 to 2020 in the core collection of Web of Science database were retrieved. The bibliometrics method was applied to analyze the number of articles published per year, journals and the first authors, countries and institutions, research fields, the annual citation frequency of cumulative published articles, highly cited articles, keywords. CiteSpace5.6.R2 software was applied to visually cluster keywords of the included articles, while VOSviewer1.6.13 software was applied to visually cluster keywords in titles and abstracts of the included articles in order to analyze research directions and development trends. Results:A total of 2 693 keloid-related articles were retrieved. From 2000 to 2020, the number of keloid-related articles published every year showed a significant upward trend. Totally 777 journals published keloid-related articles, of which Dermatologic Surgery published the most. Rei Ogawa published the largest number of keloid-related articles as the first author of 52 related articles. Keloid-related researches were conducted in a total of 98 countries, of which the United States published the largest number of related articles (613 articles), followed by China (524 articles) and Japan (107 articles). A total of 2 656 institutions conducted keloid-related research, and the institution with the largest number of related articles published was Shanghai Jiao Tong University of China (67 articles). According to the subject classification of the Web of Science database, the included articles involved 110 research fields, and the top three were dermatology, surgery, and medicine, research and experimental. The included articles were cited 47 746 times in total, and the citation frequency of cumulative published articles increased by year. The most frequently cited article (152 times) was published in 2011. There were a total of 45 571 keywords in the included literature. The top 5 keywords ranked according to the number of articles involved from high to low were keloid (588 articles), hypertrophic scar (385 articles), expression (198 articles), fibroblast (155 articles), and scar (133 articles). The keyword map visualized by CiteSpace5.6.R2 software further displayed that the research focused on the cause, performance, and composition of keloids. VOSviewer1.6.13 software analysis showed that the research direction of keloids was divided into two categories of clinical keloid management and keloid mechanism research, the initial research hotspots were mainly to explore the diagnosis and treatment of keloids from individual cases, with a preference for apparent research, while in the later stage, the focus was on the overall management of keloids, in which the mechanism research went to the molecular level. Conclusions:At present, international research interest on keloids is showing an upward trend. Both foreign (the United States, etc.) and domestic research institutions are conducting in-depth explorations of keloids. With dermatology as the leader, the research trend is gradually shifting from observational research to molecular research.