The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

Objective:To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia(AML)by network pharmacology,and to clarify the active components and their mechanisms in treating AML.Methods:The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets were predicted by SwissTargetPrediction Database.The AML-related genes and protein targets were retrieved from the SymMap Database,the GeneCards Human Gene Database,the DisGeNET Database,and the Online Mendelian Inheritance in Man(OMIM)Database.The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.The drug-active component-target network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.8.0 software,and the core genes were selected by CytoNCA plugin;the molecular docking was conducted by AutoDock software.Results:After filtering by databases,39 active components were identified,and 148 common targets between dandelion-mulberry leaf and AML were collected.The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways,positive regulation of kinase activity,and oxidative stress responses.The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT)signaling pathway,the tumor necrosis factor(TNF)signaling pathway,and the Janus kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.The key targets were identified by topological analysis including signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),recombinant human epidermal growth factor(EGF),vascular endothelial growth factor A(VEGFA),oncogene MYC,tumor protein P53(TP53),mitogen-activated protein kinase 3(MAPK3),cysteiny asparate specific protease-3(CASP3),oncogene SRC,heat shock protein 90 alpha family class A member 1(HSP90AA1),tenascin XB1(CTNNB1),phosphoinositide kinase-3 catalytic subunit alpha(PIK3CA),interleukin 6(IL-6),TNF,mitogen-activated protein kinase 1(MAPK1),and phosphatidylinositide kinase-3 regulatory subunit 1(PIK3R1).The molecular docking results showed the highest affinity pairing to be taraxerol with MYC(-8.74 kcal·mol-1),and quercetin,kaempferol,luteolin,and artemetin demonstrated good binding affinities with various targets.Conclusion:The main active components of dandelion-mulberry leaf,such as quercetin,taraxerol,kaempferol,luteolin,and artemetin,may exert the anti-AML effect by regulating AKT1,STAT3,HSP90AA1,IL-6,and MAPK1;regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Humans ; Mice ; Rats ; Cell Proliferation ; Heart/physiology* ; Mammals ; Myocardial Infarction/metabolism* ; Myocytes, Cardiac/metabolism* ; Pericardium/metabolism* ; Single-Cell Analysis ; Zebrafish/metabolism*

Objective:To explore the clinical characteristics, causes, diagnosis and treatment of transplant renal artery stenosis after pediatric-to-adult kidney transplantation.Methods:Between July 2014 and March 2019, clinical data were retrospectively reviewed for 25 en-bloc and 27 single kidney transplant cases.Results:One en-bloc(4.0%)and two single kidney recipients(7.4%)were diagnosed as renal artery stenosis at Month 13-23 months post-transplantation.It was higher than the rate of stenosis in adult-to-adult transplant cases(1.1%)during the same period.As compared with recipients without stenosis, stenotic ones had younger pediatric donors( P<0.05)and yet similar body weight of donors as well as recipients( P>0.05). The inner diameters of stenonotic sites were(1.40-1.63)mm and predominant stenotic site was proximal renal artery rather than anastomotic site.The remaining parts of major renal arteries varied from 2.31 to 4.93 mm in diameter.It was normal in children with a corresponding age.All three cases responded well to percutaneous transluminal angioplasty and stenting. Conclusions:The cause of stenosis may be an undeveloped local artery diameter due to extensive tissue dissection around artery.Therefore cautious selections of infantile single renal graft for adult recipients and preserving surrounding tissue of renal artery assist in the prevention of graft arterial stenosis.

Objective To investigate the effects and adverse reactions of apatinib in advanced gastric cancer patients.Methods Two hundred and forty cases of advanced gastric cancer patients who had failed chemotherapy were collected from January 30,2016 to November 1,2017 in the First Hospital of Zibo City of Shandong Province and the Central Hospital of Zibo City of Shandong Province.All patients took oral apatinib mesylate,850 mg/time,1 time/d,and 28 d as 1 cycle of treatment,during which clinical efficacy,adverse reaction and progression free survival (PFS) and overall survival period (OS) were evaluated.Adopting Cox regression model to analyze risk factors of PFS and OS.Results Of all 240 patients,no patient reached complete response (CR) standard,25 patients (10.4％) reached partial response (PR) standard,113 patients (47.1％) reached stable disease (SD) standard,and 102 patients (42.5％) reached progressive disease (PD) standard.Objective response rate (ORR) and disease control rate (DCR) were 10.4％ (25/240) and 57.5％ (138/240) respectively.When apatinib was taken as a 2nd line treatment,ORR and DCR were 62.5％ (5/8) and 75.0％ (6/8) respectively;as 3rd line treatment,the result came to 13.9％ (20/144) and 67.4％ (97/144);as 4th line treatment,it was 0 and 52.4％ (33/63);as 5th line treatment,it was 0 and 8.0％ (2/25).Among the various adverse effects of apatinib,the most common ones observed were skin lesion (65.8％,158/240),fatigue (57.9％,139/240),gastrointestinal reaction (45.4％,109/240),and hypertension (38.8％,93/240).Cox multivariate analysis showed that the change of treatment time (HR =5.028,95％CI:1.130-15.771,P =0.005) and body mass index (HR =21.069,95％CI:4.521-127.116,P ＜ 0.001) were the independent risk factors of PFS.BMI change (HR =6.550,95％ CI:1.080-38.455,P =0.039) was independent risk factor of OS.Conclusion For patients with advanced gastric cancer who failed with 2nd line and above chemotherapy,oral atatinib still obtain certain DCR and survival gain.Apatinib adverse reactions are various,involving a wide range of organ systems,however are generally controllable.

Objective: To compare the sedation induced by target-controlled infusion of propofol with that by propofol-remifentanil in third molar exaction surgery. Methods: 60 patients for third molar exaction were divided randomly into 2 groups(n = 30): group P(propofol group) and group PR(propofol-remifentanil group). In group P,a titrated infusion of propofol was started until the OAA/S score had reached level 3 in the patients,then the surgery began. In group PR,a infusion of remifentanil with a target plasma concentration of 1 ng /ml and a titrated infusion of propofol was started until the OAA/S score had reached level 3,then the surgery began. In all patients,the heart rate,blood pressure,respiratory rate,oxyhemoglobin saturation and narcotrend index were recorded during the operation. The reactions of the patients in the operation were recorded. The satisfaction of the patients and surgeons was asked. Results: The respiratory rate and the oxyhemoglobin saturation in group PR was lower than those in group P(P ＜ 0. 05). No obvious adverse reaction was observed in the 2 groups. The satisfaction of the patients in the 2 groups was 30 /30 and 30 /30(P＞ 0. 05). Conclusion: The sedation induced by target-controlled infusion of propofol or propofol-remifentanil in third molar extraction is safe. The sedation under target-controlled infusion of propofol-remifentanil is better than that by propofol when inhalating oxygen.

Objective To comprehensively evaluate the resuscitation effect of endotracheal intubation (ETI) ventilation and laryngeal mask airway (LMA) for out-of-hospital cardiac arrest (OHCA). Methods Databases such as Cochrane Library, PubMed, Embase, Ebsco, Elsevier, OVID, Springer, Proquest, and China biomedical literature database (CBMdisc), CNKI, Wanfang database, Chinese Science and Technology Journal Full-text Database, VIP Chinese biomedical journal database were searched from the establishment of literature database to December 2017 to study the difference of effects between ETI and LMA for patients with OHCA. The effect determination indexes included the return of spontaneous circulation (ROSC) rate, 1-month survival and 1-month neurological recovery. After evaluation of the quality of included studies and extraction of the data, the software of RevMan 5.3 was used to analyze those outcomes. Results A total of 9 articles, including 7 English, 2 Chinese;5 prospective studies and 4 retrospective studies were included. All of the literatures had high quality, and the Newcastle Ottawa scale (NOS) scored 7-9 points. The Meta-analysis showed that ETI was significantly more beneficial than LMA in improving the rate of ROSC [odds ratio (OR) = 1.51, 95% confidence interval (95%CI) = 1.42-1.62, Z = 12.35, 1 < 0.01], and 1-month survival (OR = 1.16, 95%CI = 1.06-1.26, Z = 3.41, 1 < 0.01), and there was no significant difference in 1-month neurological recovery (OR = 1.13, 95%CI = 0.96-1.32, Z = 1.49, 1 = 0.14). Conclusion ETI has higher recovery success rate and survival rate than LMA for the rescue of OHCA adult patients, but the improvement of the nervous system is unclear.

Objective To investigate the expression and clinical significance of periostin (PN) in breast cancer and its adjacent tissues.Methods We evaluated 50 women with breast cancer.We determined PN expression by immunohistochemistry and analyzed positive expression in the tumors and adjacent tissue by paticnt age,TNM stage,SBR type,pathological type,lymph node metastasis,and other factors.Results PN expression in breast cancer and cancer adjacent tissues was associated with an increase in TNM staging (P =0.024),SBR type (P =0.012),and lymphatic metastasis (P =0.035).However,there was no significant correlation between age or pathological type (P ＞ 0.05).Condusion Expression of PN in breast cancer is associated with TNM staging,SBR type,and lymph node metastasis,and is involved in the pathological progression of breast cancer.PN may be a potential prognostic marker for breast cancer.

Objective: To investigate the determinants affecting the heart rate deceleration capacity (DC) in patients with dilated cardiomyopathy (DCM). Methods: One hundred patients with DCM (DCM group) and 202 healthy subjects (control group) were respectively enrolled. Echocardiography and 24 hours electrocardiogram were performed in all subjects. DC value was compared between the two groups. Multiple regression analysis was made to evaluate the related determinants of DC ((age, sex, echocardiographic parameters including the left atrial diameter (LAD) and left ventricular ejection fraction (LVEF)). Results: (1) DC value was significantly lower in DCM group than in control group( (4.40±2.03) ms vs. (7.30±1.81) ms, P<0.01), prevalence of DC value≤4.5 ms was significantly higher in DCM group than in control group (62% vs. 6%, P<0.01). (2) DC value in the DCM group decreased in proportion to increasing LAD dimension, DC value was (5.60±2.04) ms, (4.50±2.07) ms and (3.60±1.62) ms (P<0.05) in DCM patients with LAD≤40 mm, 40 mm50 mm, respectively. (3) DC value in the DCM group was negatively related to the LAD (r=-0.366, P<0.01), positively related to the LVEF (r= 0.241, P<0.01), but not related with age and sex. Multiple factors regression analysis showed that increased LAD was related to the reduced DC values independtly. Conclusion DC value of the patients in the DCM group is decreased, which indicate the decrease of the vagus nerve tension, and increased LAD is related to the reduced DC value independtly in DCM patients.