Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.

Preliminary Exploration of Integrating Narrative Medicine into General Practice Education / 中国医学伦理学

In the context of a healthy China, strengthening humanistic literacy education for general medical students reflects the demands of the times, promotes the transformation of medical models, and has important practical significance in reducing the work burnout of general practitioners in practice. Integrating narrative medicine into general practice student education is conducive to implement the patient-centered concept of general practice, provide continuous and systematic medical services, and further improve the humanistic literacy of general practitioners. Based on these, this paper proposed the relevant paths of integrating narrative medicine into student education in general medicine, including changing educational concepts and integrating educational resources, boldly carrying out curriculum reforms and innovating educational methods, fully utilizing parallel medical records and reflective writing, as well as cultivating the habit of lifelong learning.

Mercury wet depositions study at suburban, agriculture and traffic sampling sites.

This study aimed to measure and discuss the relationship of ambient air precipitations with respect to mercury wet depositions at suburban, agriculture and traffic three characteristic sampling sites during the year of 2019. In addition, the mercury volume weighted mean concentrations (VWM) at three characteristic sampling sites were also calculated. Finally, the ambient mercury wet depositions data obtained in this study to various world sampling sites were also compared and discussed in this study. The results indicated that the average mercury wet depositions for suburban, agriculture and traffic areas were 0.62, 0.55 and 2.32 ng/m2 min, respectively. And the average mercury VWM values were 0.9, 0.72 and 1.85 ng/m2 min for suburban, agriculture and traffic sites, respectively. In addition, the highest VWM and wet depositions for mercury both occurred in March at traffic and suburban areas. And the mercury wet depositions displayed a declined trend when the month was moved from March to July at both traffic and suburban sampling sites. In addition, the relationship between wet depositions and precipitations was low to moderate correlated in traffic area, while the relationship between wet depositions and precipitations was insignificant at both suburban and agriculture areas. Moreover, the average highest mercury wet deposition occurred in Nepal when compared to the other world sites. In addition, the average value of mercury wet depositions in Nepal was about 17.23 times to that of data obtained in this study during the period of 2007-2019. Finally, the average highest VWM (ng/L) occurred in the China. In addition, the average value mercury VWM in China was about 14.82 times to that of data obtained in this study during the period of 2007-2019.

Exploratory screening of potential pan-cancer biomarkers based on The Cancer Genome Atlas database / 北京大学学报(医学版)

OBJECTIVE@#To screen potential pan-cancer biomarkers based on The Cancer Genome Atlas (TCGA) database, and to provide help for the diagnosis and prognosis assessment of a variety of cancers.@*METHODS@#"GDC Data Transfer Tool" and "GDCRNATools" packages were used to obtain TCGA database. After data sorting, a total of 13 cancers were selected for further analysis. False disco-very rate (FDR) < 0.05 and fold change (FC) >1.5 were used as the differential expression criteria to screen genes and miRNAs that were up- or down-regulated in all the 13 cancers. In the receiver operating characteristic curve (ROC curve), the area under the curve (AUC), the best cut-off value and the corresponding sensitivity and specificity were used to reflect diagnostic significance. The Kaplan-Meier method was used to calculate the survival probability and then the log-rank test was performed. Hazard ratio (HR) was calculated to reflect prognostic evaluation significance. DAVID tool were used to perform GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis for differentially expressed genes. STRING and TargetScan tools were used to analyze the regulatory network of differentially expressed genes and miRNAs.@*RESULTS@#A total of 48 genes and 2 miRNAs were differentially expressed in all the 13 cancers. Among them, 25 genes were up-regulated, 23 genes and 2 miRNAs were down-regulated. Most differentially expressed genes and miRNAs had good ability to distinguish between the cases and controls, with AUC, sensitivity and specificity up to 0.8-0.9. Survival analysis results show that differentially expressed genes and miRNAs were significantly associated with patient survival in a variety of cancers. Most up-regulated genes were risk factors for patient survival (HR>1), while most down-regulated genes were protective factors for patient survival (0 < HR < 1). The enrichment analysis of GO and KEGG showed that the differentially expressed genes were mostly enriched in biological events related to cell proliferation. In the regulatory network analysis, a total of 13 differentially expressed genes and 2 differentially expressed miRNAs had regulatory and interaction relationships.@*CONCLUSION@#The 48 genes and 2 miRNAs that were differentially expressed in 13 cancers may serve as potential pan-cancer biomarkers, providing help for the diagnosis and prognosis evaluation of a variety of cancers, and providing clues for the development of broad-spectrum tumor therapeutic targets.

Discussion for relationship between serum CA125 and heart failure / 心血管康复医学杂志

Many studies indicated that with the rise of cardiac function class in patients with heart failure (HF), serum CA125 concentration gradually rose, and it's significant positively correlated with BNP level and NYHA class. It 's reported that in HF patients with pleural effusion, serum CA125 level significantly increases, and rehospitalization rate and mortality of HF patients rise along with CA125 level. Therefore, the present article made a discussion on relationship between serum CA125 level and HF.

Diagnostic and therapeutic progress of coronary heart disease / 心血管康复医学杂志

Coronary heart disease has become a major threat of human health, and its incidence rate remains surprisingly high.In recent years, technology on its diagnosis and treatment has developed greatly.The present article made a review on related new diagnosis and treatment so as to provide reference for clinical diagnosis and treatment of coronary heart disease.

Influence of atorvastatin on levels of hsCRP, IL-6 and TNF-α in patients with acute coronary syndrome / 心血管康复医学杂志

Many researches proved that inflammation plays a decisive role in occurrence, development and prognosis of acute coronary syndrome (ACS).Atorvastatin possesses many other effects besides lipid regulation, and anti-inflammatory effect is the most significant one.Some studies indicated that atorvastatin can reduce levels of high sensitive C reactive protein (hsCRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in ACS patients, then inhibit postoperative inflammation, improve postoperative blood flow perfusion and reduce occurrence of acute coronary events.The present article made a review on influence of atorvastatin on levels of hsCRP, IL-6 and TNF-α in ACS patients.

Intervention ofFu Liu Zhen plus Moxa-box Moxibustion at Umbilicus in a Community Population of Qi Deficiency and Yang Deficiency / 上海针灸杂志

Objective To observe the action ofFu Liu Zhen (acupuncture at the six abdominal points) plus moxa-box moxibustion at umbilicus on a community population of qi and yang deficiency.Method Two hundred subjects diagnosed with qi deficiency and/or yang deficiency were randomized into a treatment group and a control group, 100 cases in each group. The two groups both received constitution-associated health education, and the treatment group was additionally intervened byFu Liu Zhen plus moxa-box moxibustion at umbilicus, while the control group didn’t receive any other intervention. The Score of Constitution in Traditional Chinese Medicine (TCM) and the number of people of each constitution were observed prior to the intervention, right after the intervention, 6 months after the intervention and 12 months after the intervention.Result In the treatment group, the scores of qi deficiency and yang deficiency after the intervention, 6 months after the intervention and 12 months after the intervention were significantly different from that prior to the intervention (P<0.01). The scores of the corresponding constitution types (qi deficiency, yang deficiency) after the intervention, 6 months after the intervention and 12 months after the intervention were significantly different from that before the intervention (P<0.01). The proportions of subjects with harmonious constitution, qi deficiency, and yang deficiency in the treatment group after the intervention, 6 months and 12 months after the intervention were significantly different from that prior to the intervention (P<0.01). The proportions of subjects with harmonious constitution, qi deficiency, and yang deficiency in the treatment group after the intervention, 6 months and 12 months after the intervention were significantly different from that in the control group (P<0.01).ConclusionFu Liu Zhen plus moxa-box moxibustion at umbilicus can improve the qi-deficiency and yang-deficiency constitutions in the community population.

The expression of hepatic carboxypeptidase E is decreased in patients with cholesterol gallstone.

BACKGROUND/AIMS: Decreased carboxypeptidase E (CPE) expression is associated with numerous pathophysiological conditions. This study aimed to investigate the potential function of hepatic CPE in cholesterol gallstone formation. PATIENTS AND METHODS: Patients with cholesterol gallstone (CGS group) and patients without cholesterol gallstones (non-CGS group) were enrolled. The serum total cholesterol, triglyceride, and biliary composition were analyzed. Eight liver samples from two patients without CGS and six patients with CGS were subjected to cDNA microarray analysis. Hepatic CPE expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemical analysis. Plasma CCK level was measured by ELISA. RESULTS: cDNA microarray identified CPE as a gene downregulated in the CGS group. RT-PCR showed that CPE mRNA level was lower in CGS group than in control (P < 0.05, t-test). Moreover, Western blot and immunohistochemistry analysis showed that CPE protein level was significantly lower in CGS group than in the control group. In addition, plasma CCK level was lower in CGS group than in the control group. A positive correlation was found between serum CCK level and hepatic CPE mRNA level (r2 = 0.713, P = 0.003). CONCLUSIONS: Down-expression of liver CPE may reduce the secretion of serum CCK and contribute to the formation of cholesterol gallstone.

Prognostic value of microRNA-145 in patients with various cancers: a meta-analysis.

BACKGROUND: MicroRNA-145 (miR-145) plays a crucial role in cancer prognosis. OBJECTIVE: This study aimed to investigate the prognostic value of miR-145 in patients with various cancers. METHODS: We pooled published literature from PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews and calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the correlation between miR-145 expression levels and survival of patients with general cancers. RESULTS: A total of 615 cases from 8 studies of multiple cancers were examined in this meta-analysis. The HR for overall survival (OS) of low miR-145 expression in multiple cancers was 1.80 (95% CI = 1.19-2.70). Furthermore, after excluding 1 study for its potential heterogeneity, the results suggested an increasing prognostic value of low miR-145 expression (HR = 2.20, 95% CI = 1.63-1.97). In addition, there was no significant difference between miR-145 expression levels and recurrence-free survival (RFS). CONCLUSION: In conclusion, our findings suggest that miR-145 expression is associated with OS in cancer patients and can serve as a promising biomarker for monitoring prognosis.

Effect of Intravenous Administration of Liposomal Prostaglandin E1 on Microcirculation in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Intervention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies have demonstrated that primary percutaneous coronary intervention (PCI) can result in reperfusion injury. This study aims to investigate the effectiveness of liposomal prostaglandin E1 (Lipo-PGE1, Alprostadil, Beijing Tide Pharmaceutical Co., Ltd.) for enhancing microcirculation in reperfusion injury. In addition, this study determined the optimal administration method for acute ST elevation myocardial infarction (STEMI) patients undergoing primary PCI.</p><p><b>METHODS</b>Totally, 68 patients with STEMI were randomly assigned to two groups: intravenous administration of Lipo-PGE1 (Group A), and no Lipo-PGE1 administration (Group B). The corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC) and myocardial blush grade (MBG) were calculated. Patients were followed up for 6 months. Major adverse cardiac events (MACE) were also measured.</p><p><b>RESULTS</b>There was no significant difference in the baseline characteristics between the two groups. The cTFC parameter in Group A was significantly lower than Group B (18.06 ± 2.06 vs. 25.31 ± 2.59, P < 0.01). The ratio of final MBG grade-3 was significantly higher (P < 0.05) in Group A (87.9%) relative to Group B (65.7%). There was no significant difference between the two groups in final TIMI-3 flow and no-reflow. Patients were followed up for 6 months, and the occurrence of MACE in Group A was significantly lower than that in Group B (6.1% vs. 25.9% respectively, P < 0.05).</p><p><b>CONCLUSIONS</b>Myocardial microcirculation of reperfusion injury in patients with STEMI, after primary PCI, can be improved by administering Lipo-PGE1.</p>

Correlation between serum MMP-2 level and severity of coronary artery disease in aged ACS patients with hyperhomocysteinemia / 心血管康复医学杂志

Objective:To explore the correlation between serum level of matrix metalloproteinase 2 (MMP-2)and se-verity of coronary artery disease in aged patients with acute coronary syndrome (ACS)complicated hyperhomocys-teinemia (HHCY).Methods:According to serum level of homocysteine (Hcy),a total of 105 aged ACS patients were selected and divided into ACS+HHCY group (n=56)and pure ACS patients (n=49),another 65 healthy in-dividuals were enrolled as healthy control group.The severity of coronary artery disease was showed by Gensini score ;enzyme linked immunosorbent assay was used to measure serum MMP-2 level in each group.Results:Com-pared with healthy control group,there were significant rise in MMP-2 level [(140.8±50.1)ng/ml vs.(442.5± 98.2)ng/ml,(297.9±86.3)ng/ml]in ACS+HHCY group and pure ACS group,P <0.01. Gensini score in ACS+HHCY group was significantly higher than that of pure ACS group [(1.9±0.2)scores vs.(1.1±0.3)scores,P<0.01].Pearson correlation analysis indicated that Gensini score was positively correlated with MMP-2 level in ACS+HHCY group (r =0.424,P <0.05).Conclusion:The serum MMP-2 level is significantly positively correla-ted with severity of coronary artery disease in aged patients with ACS complicated HHCY.

RC-3095, a gastrin-releasing peptide receptor antagonist, synergizes with gemcitabine to inhibit the growth of human pancreatic cancer CFPAC-1 in vitro and in vivo.

OBJECTIVES: Pancreatic cancer remains a lethal disease. In this study, we investigated the efficacy of a combination of gastrin-releasing peptide receptor antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1. METHODS: The antiproliferation effects of RC-3095, gemcitabine, or the combination on pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC-1 cell received injections of the vehicle (control), RC-3095 (20 µg, subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days), or the combination of RC-3095 and gemcitabine for 4 weeks. The histological changes and protein expression were tested using immunohistochemistry and Western blotting. RESULTS: Treatment with the combination in culture exhibited a powerful inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095 or gemcitabine significantly reduced the volume and weight of tumors after 4 weeks of treatment, as compared with controls. The combination more potently inhibited the tumor growth than either agent used individually. Immunohistochemistry and Western blotting showed gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination. CONCLUSIONS: Our data suggested that the combination could be considered for the possible new approaches for treatment of pancreatic cancers.

Effects of hypoxia-inducible factor-1α silencing on drug resistance of human pancreatic cancer cell line Patu8988/5-Fu.

The present study aimed to investigate the mechanism and the possible approaches of solving drug resistance by silencing hypoxia-inducible factor-1 alpha of human pancreatic cancer cell line Patu8988/5-Fu cultured in hypoxia. The effective jamming fragment screened by RT-PCR for silencing HIF-1α gene was transfected into pancreatic cancer cells Patu8988/5-Fu through lentivirus. RT-PCR results showed that the effective jamming fragments for HIF-1α in lentivirus transfection was Wtl-mus-1202(C546). Combined MTT with JC-1 fluorescence staining flow cytometric analysis, the concentration of 200 µmol/L CoCl2 for 8 h was chosen to mimic hypoxia cell environment. The drug resistance significantly enhanced in response to hypoxia in Patu8988/5-Fu (p<0.05), and silence HIF-1α could reverse the multidrug resistance (P<0.05). In the Patu8988/5-Fu cells, HIF-1α and MDR1 significantly increased in response to hypoxia (p<0.05). The inhibition of HIF-1α expression synergistically downregulated the expression of the MDR1 gene in Patu8988/5-Fu cells (p<0.05). HIF-1α expression was positively correlated with the MDR1 expression (p<0.05). The upregulation of the HIF-1α and MDR1 gene expression caused by hypoxia was related with the generation of multi-drug resistance of Patu8988/5-Fu, targeted silencing HIF-1α may be a kind of way to reverse the chemotherapy drug resistance.

Safety and feasibility of transulnar versus transradial artery approach for coronary catheterization in non-selective patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Transradial approach catheterization is now widely used in coronary angiography and angioplasty. The ulnar artery, which is one of the two terminal branches of the brachial artery, may be a potential approach for cardiac catheterization. The aim of this study was to evaluate the safety and feasibility of a transulnar approach for coronary catheterization in non-selective patients.</p><p><b>METHODS</b>A total of 535 consecutive patients were randomly assigned to transulnar approach (TUA) group (n = 271) or transradial approach (TRA) group (n = 264) upon arrival at the catheterization laboratory. Allen's test and inverse Allen's test were not routinely performed. Ultrasound-Doppler assessment of the forearm artery was performed before the procedure, two days after the procedure, and 30 days after the procedure. The primary endpoints of study were the rate of successful artery cannulation and the access-site related complications. The secondary endpoints included the number of needle punctures, total time for the procedure, and major adverse cardiac events (MACE).</p><p><b>RESULTS</b>Successful puncture of the objective artery was obtained in 91.5% of the patients in the TUA group, and 95.1% of the patients in the TRA group (P > 0.05). There was no significant difference in hematoma complications between the two groups (7.7% vs. 4.2%, P = 0.100). A motor abnormality of the hand was observed in one patient in the TUA group. There were no arteriovenous fistula or pseudoaneurysm observed in our study. Three (1.1%) patients in the TUA group and 8 (3.0%) patients in the TRA group had occlusion of the access artery (P = 0.137), but none of the patients had symptoms or signs of hand ischemia. There were no significant differences in MACE between the two groups during follow-up.</p><p><b>CONCLUSION</b>The transulnar approach is an effective and safe technique for coronary catheterization in non-selective patients.</p>

Treatment of floating knee injury / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical outcome of floating knee injury treated by open reduction and internal fixation.</p><p><b>METHODS</b>The course of treatment of floating knee in 78 cases by open reduction and internal fixation were reviewed. There were 59 males and 19 females, aged from 17 to 58 years old, with an average age of 37.5 years. Intramedullary nail, pressure plate hollow screw, multi-function single side external fixation holder and other internal fixature were used in the operation. Early exercises were followed postoperatively.</p><p><b>RESULTS</b>All patients were followed-up for 8 to 35 months (mean 18.6 months). According to the criterion of Karlström, of the 48 cases with femoral shaft fracture, 45 were excellent and 3 were good. In the 11 cases of bimalleolar fracture, 5 were excellent, 3 good, 1 fair and 2 bad. Of the 19 cases of mixed fracture, 9 were excellent,6 good, 3 fair and 1 bad.</p><p><b>CONCLUSION</b>Strict sterilization, non-invasion and standard internal and external fixation could make the fracture anatomical reduction and firm fixation. It is beneficial to early rehabilitation exercise. Complications such as malunion, and stiff joint could be avoided. The clinical outcome were satisfactory.</p>