Objective To investigate the effect of dexmedetomidine(Dex)on inflammatory injury in rats with lipopolysaccharide(LPS)-induced myocarditis(Myo)by regulating AMP-activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear factor κB(NF-κB)signaling pathway.Methods Rats were randomly divide into the NC group,the Myo group,and the L-Dex group(10 μg/kg Dex),the M-Dex group(30 μg/kg Dex),the H-Dex group(50 μg/kg Dex),the AICAR group(100 mg/kg AMPK/SIRT1/NF-κB signal pathway activator),the H-Dex+GSK690693 group(50 μg/kg Dex+0.2 μmol/kg AMPK/SIRT1/NF-κB signal pathway inhibitor GSK690693),with 10 rats in each group.M-mode echocardiography system was used to evaluate the cardiac function of rats;ELISA kit was used to detect the levels of serum interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),and malondialdehyde(MDA)in rats;TUNEL staining was used to observe cell apoptosis;HE staining was used to observe the pathological changes of myocardial tissue;RT-qPCR was used to detect the mRNA expression of C-X-C motif chemokine ligand 1(CXCL1),C-X-C motif chemokine ligand 2(CXCL2),and vascular cell adhesion molecule-1(VCAM-1)in rat myocardial tissue;Western blot was used to detect the expression of AMPK/SIRT1/NF-κB pathway-related proteins in rat myocardial tissue.Results There was no abnormal change in cardiomyocytes in the NC group,and cardiomyocytes in the Myo group showed deformation,necrosis,inflammatory cell infiltra-tion,and mesenchymal congestion;necrosis,inflammatory cell infiltration,and mesenchymal congestion in the L-Dex group,the M-Dex group,the H-Dex group,and the AICAR group were improved compared with that in the Myo group;changes in cardiomyocytes in the H-Dex group and the AICAR group were similar to those in the NC group,and changes in cardiomyocytes in the H-Dex+GSK690693 group were similar to those in the Myo group.Compared with the NC group,the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the Myo group were obviously decreased(P<0.05),left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously increased(P<0.05).Compared with the Myo group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the L-Dex group,the M-Dex group,the H-Dex group and the AICAR group were obviously increased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,expression levels of IL-1β,IL-6,TNF-α,MDA,CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB,NF-κB p65 and cardiomyocyte apoptosis rate were obviously decreased(P<0.05),and the effects were more obvious with the increase of the dosage of Dex.There was no significant difference in the above results between the AICAR group and the H-Dex group(P>0.05).Compared with the H-Dex group,the LVEF,LVFS,expression levels of SOD,p-AMPK/AMPK,p-SIRT1/SIRT1 in the H-Dex+GSK690693 group were obviously decreased(P<0.05),LVESV,LVEDV,LVESD,LVEDD,levels of IL-1β,IL-6,TNF-α,MDA,cardiomyocyte apoptosis rate,the expression of CXCL1,CXCL2,VCAM-1,p-NF-κB/NF-κB and NF-κB p65 protein were obviously increased(P<0.05).Conclusion Dex may alleviate LPS-induced inflammatory injury in Myo rats by up-regulating AMPK/SIRT1/NF-κB signaling pathway.

AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.

Brasilicardin A, a diterpene glycoside isolated from pathogenic actinomycete Nocardia brasiliensis IFM 0406, has become a novel immunosuppressant candidate due to its significant immunosuppressive activity, low toxicity and unique mechanism of action. However, brasilicardin A and its analogues have become a research hotspot to the development of this promising immunosuppressant because of the low-yield production in the natural pathogenic producer and the synthetically challenging skeleton. According to the reported biosynthetic pathway of brasilicardin A, the function of involved diterpene synthase was analyzed by bioinformatics. Then the genes bra1-5 that synthesize the brasilicardin A skeleton were directionally amplified from the pathogenic strain N. brasiliensis IFM 0406, and heterologous expression was achieved successfully in Streptomyces albus R1. The compounds were isolated and purified by using various column chromatographies including silica gel column chromatography and semi-preparative HPLC. Six new brasilicardins were established and named brasilicardin H-M. The activity of brasilicardins was screened using lipopolysaccharide (LPS)-activated mouse primary macrophage inflammation model. Brasilicardin H-M exhibited good inhibitory activity on nitric oxide (NO) release with IC₅₀ values of 28.24 ± 3.70, 37.44 ± 2.00, 39.85 ± 4.02, 26.77 ± 4.40, 65.25 ± 1.48 and 15.24 ± 2.72 μmol·L^-1, respectively (indomethacin as the positive control with IC₅₀ value of 34.28 ± 4.10 μmol·L^-1). The results indicated that six compounds had potential anti-inflammatory activity. This study laid a foundation for the elucidation of the brasilicardin A biosynthetic pathway and evaluation of the structure-activity relationship as well as new drug developments.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

AIM: To explore the value of ocular trauma score(OTS), initial visual acuity, and ocular structural parameters in the assessment of healing visual acuity from ocular trauma.METHOD: A total of 302 cases(302 eyes)of ocular trauma were selected as subjects, which were accepted and issued clear appraisal opinions by the Academy of Forensic Science from June 2015 to June 2021. The subjects were grouped according to the healing best corrected visual acuity(BCVA)from ocular trauma. Group Ⅰ included 63 cases(63 eyes)with BCVA <3.7; Group Ⅱ included 70 cases(70 eyes)with 3.7≤ BCVA <4.5; Group Ⅲ included 78 cases(78 eyes)with 4.5≤ BCVA <4.9; Group Ⅳ included 91 cases(91 eyes)with BCVA≥4.9. In addition, 77 cases(77 healthy eyes)of ocular trauma were selected as the control group, namely Group Ⅴ. The healing BCVA and ocular structural parameters from ocular trauma and theirs correlation were analyzed, and the random forest(RF)and support vector machine(SVM)model of healing visual acuity was established by the IBM SPSS Modeler 18.0.RESULTS: The initial visual acuity, OTS, the grading of corneas, lenses, and fundus, and the thickness of the retinal never fiber layer of ocular trauma patients were correlated with the healing BCVA(P<0.01). There were significant differences in ocular structural parameters among groups, except the central subfield thickness(P<0.001). The SVM model had higher accuracy of predicting healing visual acuity than the RF model, and the accuracy rate was over 80% when the error was within 0.15.CONCLUSION:OTS and ocular structural examination can provide effective information for the clinical forensic medicine appraisal of visual dysfunction after ocular trauma, and they are valuable in discriminating camouflage of visual dysfunction.

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.
Male ; Female ; Humans ; Mitral Valve Insufficiency/surgery* ; Thoracotomy ; Retrospective Studies ; Cardiomyopathy, Hypertrophic/surgery* ; Ventricular Septum/surgery* ; Treatment Outcome ; Minimally Invasive Surgical Procedures/methods*

Objectives: To analyze the long-term survival of patients with localized renal cell carcinoma after partical nephrectomy. Methods: The clinicopathological records and survival follow-up data of 2 046 patients with localized renal cell carcinoma, who were treated with partial nephrectomy from August 2001 to February 2021 in the Department of Urology, Sun Yat-sen University Cancer Center, were retrospectively analyzed. There were 1 402 males and 644 females, aged (M(IQR)) 51 (19) years (range: 6 to 86 years). The primary end point of this study was cancer-specific survival. Survival curves were estimated using the Kaplan-Meier method, and the difference test was performed by Log-rank test. Univariate and multivariate Cox analysis were fitted to determine factors associated with cancer-specific survival. Results: The follow-up time was 49.2 (48.0) months (range: 1 to 229 months), with 1 974 patients surviving and 72 dying. The median cancer-specific survival time has not yet been reached. The 5- and 10-year cancer specific survival rates were 97.0% and 91.2%, respectively. The 10-year cancer-specific survival rates for stage pT1a (n=1 447), pT1b (n=523) and pT2 (n=58) were 95.3%, 81.8%, and 81.7%, respectively. The 10-year cancer-specific survival rates of patients with nuclear grade 1 (n=226), 2 (n=1 244) and 3 to 4 (n=278) were 96.6%, 89.4%, and 85.5%, respectively. There were no significant differences in 5-year cancer-specific survival rates among patients underwent open, laparoscopic, or robotic surgery (96.7% vs. 97.1% vs. 97.5%, P=0.600). Multivariate analysis showed that age≥50 years (HR=3.93, 95%CI: 1.82 to 8.47, P<0.01), T stage (T1b vs. T1a: HR=3.31, 95%CI: 1.83 to 5.99, P<0.01; T2+T3 vs. T1a: HR=2.88, 95%CI: 1.00 to 8.28, P=0.049) and nuclear grade (G3 to 4 vs. G1: HR=2.81, 95%CI: 1.01 to 7.82, P=0.048) were independent prognostic factors of localized renal cell carcinoma after partial nephrectomy. Conclusions: The long-term cancer-specific survival rates of patients with localized renal cancer after partial nephrectomy are satisfactory. The type of operation (open, laparoscopic, or robotic) has no significant effect on survival. However, patients with older age, higher nuclear grade, and higher T stage have a lower cancer-specific survival rate. Grasping surgical indications, attaching importance to preoperative evaluation, perioperative management, and postoperative follow-up, could benefit achieving satisfactory long-term survival.

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 μmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.
Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Apigenin ; Molecular Docking Simulation ; Alkaloids ; Quinolizines ; RNA, Messenger ; ErbB Receptors