Objective To investigate the prognostic factors for patients with hepatitis B virus-related acute-on-chronic liver failure,and to provide a basis for clinical diagnosis and treatment.Methods A total of 172 patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure who were admitted to The First Hospital of Jilin University from January 1,2006 to January 1,2016 and had complete medical records and follow-up data were enrolled,and a retrospective analysis was performed for their clinical data and laboratory markers to determine prognostic factors.The independent-samples t test was used for comparison of continuous data between groups,the chi-square test was used for comparison of categorical data between groups,and a multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis to screen out independent risk factors for the prognosis of patients with HBV-related acute-on-chronic liver failure.Results The multivariate logistic regression analysis was performed for the indices determined to be statistically significant by the univariate analysis,and the results showed that the prognostic factors were total bilirubin (TBil),prothrombin time activity (PTA),Na +,total cholesterol (TC),Child-Turcotte-Pugh (CTP) score,age ≥50 years,the presence of liver cirrhosis,bilirubin-enzyme separation,and complications.The multivariate regression analysis was performed for the complications determined to affect prognosis by the univariate analysis,and the results showed that the complications as risk factors were hepatic encephalopathy,hepatorenal syndrome,and infection.Conclusion TBil,PTA,Na +,TC,CTP score,age ≥50 years,the presence of liver cirrhosis,bilirubin-enzyme separation,and complications are independent risk factors for the prognosis of patients with HBV-related acute -on-chronic liver failure.Liver failure patients with hepatic encephalopathy,hepatorenal syndrome,and infection tend to have poorer prognosis.Therefore,early judgment of the prognosis of patients with liver failure is of great importance in the prevention and treatment of related complications.

Objective: To investigate the plasma levels of interleukin-6 (IL-6), C-reactive protein (CRP), D-dimer (D-D) and fibrinogen (Fib) among patients with pneumoconiosis, so as to provide insights into the prevention of thrombosis among patients with pneumoconiosis. Methods: Ninety-six male coal workers with stable-stage pneumoconiosis admitted to China Pingmei Shenma Group Occupational Disease Prevention and Control Hospital from February 2019 to February 2021 were included in the pneumoconiosis group, and 43 male healthy volunteers in the hospital during the same period were selected as the control group. The plasma D-D, Fib, IL-6 and CRP levels were detected from subjects in the two groups. The associations of plasma D-D and Fib levels with IL-6 and CRP levels were examined using Pearson correlation analysis among pneumoconiosis patients. Results: Participants in the pneumoconiosis group and the control group had a mean age of (52.91±3.89) and (52.64±4.12) years, D-D of (1.28±0.91) and (0.44±0.11) mg/L, Fib of (4.41±0.98) and (2.88±0.61) g/L, IL-6 of (0.63±0.19) and (0.42±0.06) ng/L and CRP of (3.30±1.65) and (1.35±0.12) mg/L, respectively. Higher plasma D-D, Fib, IL-6 and CRP levels were detected in the pneumoconiosis group than in the control group (all P<0.05). The plasma D-D level correlated positively with IL-6 level among pneumoconiosis patients (r=0.347, P<0.001). Conclusion High plasma IL-6, CRP, D-D and Fib levels are detected among patients with pneumoconiosis, and the plasma D-D level correlates positively with IL-6 level among patients with pneumoconiosis.

Background and purpose: The previous work of this study has showed that the treatment of liver cancer cells with emodin could induce endoplasmic reticulum (ER) stress and apoptosis. Given the cross-talk between ER stress and autophagy, this study aimed to investigate whether blockage of autophagy, a defense mechanism against environmental stress, could improve the killing effect of emodin on liver cancer cells. Methods: The CYTO-ID auto-phagy detection kit and Western blot were used to determine autophagy in liver cancer cells. After combined treatment with chloroquine (CQ) and emodin, cancer cell survival was analyzed by ATPlite assay and clonogenic assay. Apoptosis was detected by both flow cytometry analysis and Western blot. Results: Autophagy could be induced in liver cancer cells after treatment with emodin. Inhibition of autophagy significantly increased growth-inhibitory effect of emodin on both HepG2 and Huh7 cancer cells. The combination treatment with CQ and emodin promoted remarkable apoptosis in liver cancer cells, evidenced by the increase in the percentage of cells in sub-G1 phase and the higher expression lever of cleaved caspase-3. Conclusion: Therapeutically targeting autophagy is capable of enhancing cytotoxicity of emodin in liver cancer cell lines.

Mother-to-child vertical transmission is the main mode of transmission of chronic hepatitis B in China. The probability of failure in blocking vertical transmission is about 10% in pregnant mothers with a high viral load, and therefore, correct management of hepatitis B virus (HBV) is of great importance during pregnancy. In addition, viral treatment during pregnancy should take into account the risk of vertical transmission, the health of pregnant women, and the safety of fetus, and each treatment method or prevention option needs to be carefully evaluated. Reasonable antiviral methods, drug selection, and drug withdrawal time can reduce the probability of mother-to-child transmission. This article summarizes the modes of mother-to-child vertical transmission of chronic hepatitis B and related blocking strategies, so as to provide a reference for improving the blocking rate of vertical transmission of HBV.

Objective:To observe the changes in brain magnetic resonance imaging (MRI) in patients with major depressive disorder (MDD) after modified electroconvulsive therapy (MECT) relative to before treatment.Methods:A total of 105 patients with MDD who received treatment in Hangzhou Seventh People's Hospital and Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine from June 2017 to June 2019 were included in this study. The brain MRI data pre- and post-MECT were collected. These patients were divided into study group (abnormal brain structure, n = 51) and control group (normal brain structure; n = 54) according to brain structure pre-treatment as shown on MRI. Clinical efficacy, scores of the Hamilton Rating Scale for Depression and Hamilton Rating Scale for Anxiety pre and post-treatment, and the incidence of complications were compared between the two groups. Results:MRI data revealed that 51 patients had abnormal brain structure, including 16 patients with hippocampal atrophy, 18 patients with brain volume reduction, 10 patients with intracranial cyst, and 7 patients with large occipital cistern. These patients had no obvious changes in brain structure after MECT compared with before MECT. The age of onset was lower in the study group than in the control group [(24.15 ± 1.64) years vs. (29.33 ± 2.71) years, t = -7.751, P < 0.05]. The proportion of female patients (57.4% vs. 47.1%), the proportion of patients with a family history of MDD (81.5% vs. 56.9%), and the proportion of patients with psychotic symptoms (55.6% vs. 35.3%) were significantly higher in the study group than in the control group ( χ2 = 4.96, 7.50, 4.33, all P < 0.05). Multivariate logistic regression showed that family history was a factor unrelated to MDD ( P = 0.997). Abnormal brain structure in patients with MDD was negatively correlated with age ( OR = 3.89, 95% CI = 2.083 - 7.281, P < 0.01) and it was positively correlated with sex and psychotic symptoms ( OR = 12.05, 0.08, 95% CI = 2.063 - 70.439, 0.010 - 0.698, both P < 0.05). The Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety scores decreased after MECT in both groups (both P < 0.05). The proportions of patients having dizziness/headache (50.98% vs. 27.78%), vomiting (43.14% vs. 22.22%), muscle soreness (29.41% vs. 11.11%), delirium (23.53% vs. 7.41%), and memory impairment (64.71% vs. 33.33%) were significantly higher in the study group than in the control group ( χ2 = 5.93, 5.24, 5.49, 5.27, 10.33, all P < 0.05). Conclusion:Most patients with MDD have an abnormal brain structure. Female patients at a low age of onset with psychotic symptoms tend to have an abnormal brain structure. MECT can greatly improve depressive symptoms and has no obvious impact on brain structure. Patients with MDD who have an abnormal brain structure are more likely to have complications.

Mouse double minute 2 (Mdm2) gene was isolated from a cDNA library derived from transformed mouse 3T3 cells, and was classified as an oncogene as it confers 3T3 and Rat2 cells tumorigenicity when overexpressed. It encodes a nucleocytoplasmic shuttling ubiquitin E3 ligase, with its main target being tumor suppressor p53, which is mutated in more than 50% of human primary tumors. Mdm2's oncogenic activity is mainly mediated by p53, which is activated by various stresses, especially genotoxic stress, via Atm (ataxia telangiectasia mutated) and Atr (Atm and Rad3-related). Activated p53 inhibits cell proliferation, induces apoptosis or senescence, and maintains genome integrity. Mdm2 is also a target gene of p53 transcription factor. Thus, Mdm2 and p53 form a feedback regulatory loop. External and internal cues, through multiple signaling pathways, can act on Mdm2 to regulate p53 levels and cell proliferation, death, and senescence. This review will focus on how Mdm2 is regulated under genotoxic stress, and by the Akt1-mTOR-S6K1 pathway that is activated by insulin, growth factors, amino acids, or energy status.
3T3 Cells ; Animals ; Apoptosis ; Cell Proliferation ; Cellular Senescence ; DNA Damage ; Energy Metabolism ; Feedback, Physiological ; Gene Library ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Mice ; Molecular Targeted Therapy ; Mutation ; Neoplasms ; genetics ; metabolism ; Proto-Oncogene Proteins c-mdm2 ; genetics ; metabolism ; Ribosomal Protein S6 Kinases, 90-kDa ; genetics ; metabolism ; Signal Transduction ; genetics ; TOR Serine-Threonine Kinases ; genetics ; metabolism ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Ubiquitin-Protein Ligases ; genetics ; metabolism

Somatostatin, also called somatotropin release-inhibiting factor (SRIF), is a kind of neurotransmitter, neuromodulator and neurotrophic factor, which participates in a variety of physiological functions in the central nervous system by activating the five G-protein-coupled receptors (sst 1-sst 5). SRIF and its receptors are extensively expressed and distributed in retina.Activation of SRIF receptors modulates voltage-gated K + and Ca 2+ channels, and regulates multiple intracellular signaling pathways in retinal cells, then influences neurotransmitter release and synaptic transmission, which plays an important role in the regulation of retinal visual information processing.In addition, SRIF and its receptors may provide protective effects against retinal injuries, such as retinal ischemia, excitotoxic injury and diabetic retinopathy.In this article, connected with related previous researches of our team, the distribution of SRIF and its receptor in retina, as well as the role of SRIF and its receptor in the physiological regulation and neuroprotection of retina were reviewed.

OBJECTIVE To study pharmacodynamics and potential mechanism of Blumea balsamifera total flavonoids against acute myocardial infarction （AMI） model rats. METHODS AMI model of SD rats was established by ligating anterior descending branch of left coronary artery. Fifty model rats were randomly divided into model group （0.8% carboxymethyl cellulose solution）， positive control group （Compound danshen tablet， 300 mg/kg）， B. balsamifera total flavonoids low-dose， medium-dose and high- dose groups （3， 10， 30 mg/kg）， with 10 rats in each group. Other 10 rats were included in sham operation group （0.8% carboxymethyl cellulose solution）. After 1 day of surgery， they were given relevant medicine 3 mL/kg intragastrically， once a day， for 4 consecutive weeks. The changes of S-T segment were recorded before and after operation， after weekly intragastric administration. The hemodynamic indexes of rats were all determined， i.e. systolic blood pressure （SBP）， diastolic blood pressure （DBP）， mean arterial pressure （MAP）， left ventricular systolic pressure （LVSP）， left ventricular end diastolic blood pressure （LVEDP）， maximal left ventricular pressure rising rate （+LVdp/dtmax）， maximal left ventricular pressure decreasing rate （－LVdp/ dtmax）. The levels of serum myocardial enzymes [lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB）] and inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β] were determined. The myocardial infarction rate of rats and the phosphorylation levels of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） proteins in myocardial tissue were determined. RESULTS Compared with model group， S-T segments of electrocardiogram were all decreased significantly in administration groups （P＜0.05）. SBP， DBP， MAP， LVSP， +LVdp/dtmax， －LVdp/dtmax， and ratio of p-PI3KTyr607/ PI3K， p-AktThr308/Akt， p-Aktser473/Akt were increased significantly in B. balsamifera total flavonoids medium-dose and high-dose groups （P＜0.05）. The levels of LVEDP， serum myocardial enzymes and inflammatory factors， myocardial infarction rate were all decreased significantly （P＜0.05）. CONCLUSIONS balsamifera total flavonoids can improve cardiac function of AMI model rats， the mechanism of which may be associated with inhibiting the expression of inflammatory factor and activating PI3K/Akt signaling pathway.

Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma. Here, we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension (COH). In COH retinas, the microglial proliferation that occurred was inhibited by the P2X7 receptor (P2X7R) blocker BBG or P2X7R knockout, but not by the P2X4R blocker 5-BDBD. Treatment of primary cultured microglia with BzATP, a P2X7R agonist, mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway. Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration, which was completely blocked by 5-BDBD. In vivo and in vitro experiments demonstrated that ATP, released from activated Müller cells through connexin43 hemichannels, acted on P2X7R to induce microglial proliferation, and acted on P2X4R/P2X7R (mainly P2X4R) to induce microglial migration. Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
Adenosine Triphosphate/pharmacology* ; Animals ; Cell Proliferation ; Glaucoma/metabolism* ; Mice ; Microglia/metabolism* ; Receptors, Purinergic P2X4/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Retinal Ganglion Cells/metabolism*

Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity, is a key regulator of cytoskeletal reorganization in dendrites and spines. Here, we investigated whether and how Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO did not affect spine-like branch density in single dendrites, but significantly reduced the dendritic complexity, which resulted in a decrease in the total number of dendritic spine-like branches. These results suggest that Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.