Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Objective To investigate the effect of spleen on hepatic macrophages mediated activation of hepatic stellate cells(HSCs)in mice with liver fibrosis.Methods Eighteen male C57BL/6 mice were randomly divided into three groups.Mice in Group A and Group B were injected intraperitoneally with CCl4 to establish liver fibrosis mouse model,while those in Group C were injected with corn oil as normal control.Four weeks later,mice with liver fibrosis received splenectomy(Spx)or sham operation(Sham),respectively.After continuous injection for 2 weeks,liver homogenates(L-Homo)were prepared and liver cells were isolated from the three groups.Expressions of IL-1β,IL-13,TGF-β,TNF-α,PDGF-β and VEGF in the liver homogenates of the three groups were detected by Luminex multifactor analysis.The expressions of these cytokines in liver macrophages(L-Mψ)and other non-parenchymal cells of Sham and Spx mice were analyzed by Real-time quantitative PCR(RT-qPCR)and flow cytometry.Macrophage cell line RAW264.7 or bone marrow-derived macrophages(BMDMs)were treated with liver homogenates from the Sham and Spx groups.Then the differently treated RAW264.7 cells were analyzed for mRNA expressions of cytokines and glutamine metabolism-related molecules by RT-qPCR,or transwell co-cultured with hepatic stellate cell line JS1.After co-culture,the survival and extracellular matrix expression of JS1 cells were analyzed.For comparison,Student's t test(between two groups)or one-way analysis of variance(among multiple groups)were used.Results Compared with normal control group,the concentrations of IL-1β,IL-13,TGF-β and TNF-α in the L-Homo of model group were significantly increased and showed higher levels in Sham group than in Spx group.Moreover,the hepatic macrophages were indicated as the major source of these cytokines.Consistently,macrophages treated with liver homogenate of Sham mice had increased expressions of IL-1β,TGF-β and TNF-α and glutaminase(GLS).After co-culture with macrophages treated with liver homogenate of Sham group rather than Spx group,JS1 expressed higher expressions of α-SMA and collagens.Conclusion The spleen is involved in regulating the secretion of cytokines by hepatic macrophages and enhancing their ability to activate hepatic stellate cells.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.

italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

The common risks of artificial intelligence-aided medical detection devices during the clinical application were analyzed.Some measures were put forward such as improving the design of the devices,ensuring data security and enhancing social and legal supervision,and references were provided for efficiently integrating clinical and data resources and achieving safety during the clinical application of medical devices.[Chinese Medical Equipment Journal,2024,45(11):77-82]

Objective To investigate the differences in clinical characteristics among children on prolonged mechanical ventilation(PMV)due to different primary diseases.Methods A retrospective analysis was performed on the clinical data of 59 pediatric patients requiring PMV from July 2017 to September 2022.According to the primary disease,they were divided into respiratory disease(RD)group,central nervous system(CNS)group,neuromuscular disease(NMD)group,and other disease group.The four groups were compared in terms of general information,treatment,and outcome.Results There were significant differences among the four groups in age,body weight,Pediatric Logistic Organ Dysfunction-2(PELOD-2)score,Pediatric Risk of Mortality Ⅲ(PRISM Ⅲ)score,analgesic and sedative treatment,nutrition supply,rehabilitation treatment,tracheotomy,successful ventilator weaning,and outcomes(P＜0.05).Compared with the RD group,the CNS group and the other disease group had a significantly higher age and a significantly higher proportion of children receiving rehabilitation treatment,and the CNS group had a significantly higher proportion of children receiving tracheotomy(P＜0.008).Compared with the other disease group,the CNS group and the NMD group had significantly lower PELOD-2 and PRISM Ⅲ scores,and the CNS group had a significantly higher proportion of children with successful ventilator weaning and a significantly higher proportion of children who were improved and discharged(P＜0.008).Conclusions There are differences in clinical characteristics among children receiving PMV due to different etiologies.Most children in the RD group have a younger age,and children in the CNS group have a relatively good prognosis.

Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Cardiac contractility modulation(CCM),as a new implantable electronic therapy device for treating chronic heart failure with reduced ejection fraction(HFrEF),has rapidly become a hot topic in the cardiovascular field due to its ability to enhance ventricular myocardial contractility,improve patients'symptoms and signs,cardiac function indexes and even long-term prognosis.This article reviews the mechanism and clinical studies of CCM in treating HFrEF,and based on its mechanism and signal transduction algorithm,further analyzes and prospects its efficacy in patients with heart failure with preserved ejection fraction,cardiac resynchronization therapy non-response,and HFrEF with concomitant atrial fibrillation,aiming to promote CCM to meet the needs of more diverse clinical situations in heart failure patients.

Objective To observe the value of Zero-Shot Noise2Noise(ZS-N2N)based on Z-axis correlation for reducing noise of low dose CT(LDCT)images.Methods CT data of the cancer imaging archive were enrolled,including normal dose CT(NDCT)images and LDCT images,with 3 sets of chest and 3 sets of abdominal images.Noise on LDCT images were reduced with ZS-N2N method based on Z-axis correlation,and the peak signal-to-noise ratio(PSNR),structural similarity(SSIM)and time-consuming of reducing noise were compared with those of Self2Self,simple ZS-N2N and traditional Block-matching and 3D filtering(BM3D).Results After reducing noise,noise on Self2Self denoised images remained significant,the structure edges on BM3D denoised images were blurry with some details lost,while simple ZS-N2N and ZS-N2N based on Z-axis correlation denoised images preserved more details and had better quality.PSNR and SSIM of Self2Self denoised images were poor and the time-consuming were longer.PSNR,SSIM and time-consuming of the other 3 methods were similar,among which PSNR of ZS-N2N based on Z-axis correlation were slightly higher than BM3D and simple ZS-N2N,but the time-consuming were also slightly longer.Conclusion ZS-N2N based on Z-axis correlation had high value for reducing noise of LDCT images.

We reported the comprehensive treatment of an elderly critically ill patient with pelvic fracture.The functions and quality of life of the patient were recovered after collaborative nursing by both family and hospital according to the general practice principle of both mental and physical rehabilitation.We summarized the diagnosis and treatment strategies of this case,aiming to provide reference for the clinical treatment of such cases.
Humans ; Aged ; Hip Fractures/rehabilitation* ; Quality of Life ; Multiple Organ Failure