BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective To explore the prognostic impact and clinical application value of therapeutic plasma exchange(TPE)intervention timing and liver injury periodization in patients with exertional heat stroke(EHS).Methods Data of 127 EHS patients from the First Medical Center of the General Hospital of the People′s Liberation Army from January 2011 to December 2023 were collected,then divided into the death group and the survival group based on therapeutic outcomes and into 5 stages according to the dynamic changes of ALT,AST,TBIL and DBIL.According to propensity score matching analysis,11 patients in the survival group and 12 patients in the death group were included in the statistical analysis,and 20 of them were treated with TPE.The changes in indicators and clinical outcomes before and after TPE were observed,in order to evaluate the impact of intervention timing on prognosis.Results Among the 23 patients,14 had no liver injury or could progress to the repair phase,resulting in 3 deaths(with the mortality rate of 21.43%),while 9 patients failed to pro-gress to the repair phase,resulting in 9 deaths(with the mortality rate of 100%),with significant differences(P＜0.05).The mortality rate of the first TPE intervention before the third stage of liver injury was 23.08%(3/13),while that of interven-tion after reaching or exceeding the third stage was 85.71%(6/7),and the difference was statistically significant(P＜0.05).Conclusion TPE should be executed actively in EHS patients combined with liver injury before the third phase to lock its pathological and physiological processes,thereby improving prognosis and reducing mortality.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Objective:To report 2 young infants of sodium channel related epilepsy with SCN2A gene mutation, and to discuss the clinical characteristics of the disease and the efficacy and safety of lacosamide combined with the literature.Methods:Corresponding information of 2 children hospitalized in the Department of Neurology of Hunan Children′s Hospital in July 2021 and October 2021 was collected, including the symptoms, comprehensive physical examination, blood, cerebrospinal fluid, imaging, electrophysiological examination, diagnosis and treatment process, response to treatment and other clinical data, as well as the sequencing results of the whole exome of the children. The efficacy and safety of lacosamide were analyzed, and the related literatures of the Biomedical Literature Database, Wanfang Data Knowledge Service Platform and Chinese Knowledge Infrastructure Database were searched and reviewed.Results:Both of the 2 cases were girl. Their onset age was within 3 months. The initial symptoms were frequent convulsions and backward development. There was no structural abnormality in the head image. The convulsions could not be controlled according to conventional multidrug treatment. The seizures were quickly controlled with lacosamide. Now they have been followed up for 6 months. No obvious adverse reactions were found. Case 1 gene test results showed the SCN2A gene (chr2:166152333-166246334) heterozygous deletion, SCN1A gene (chr2:166847754-16693013) heterozygous deletion, the deletion size being about 5.72 Mb. Case 2 gene test results showed new missense mutation of SCN2A (c.1285G>A, p.Glu429Lys). There were dozens of seizures every day. They were treated with valproic acid, oxcarbazepine and levetiracetam successively. The seizures could not be controlled. Three focal seizures originated in the left temporal region were detected by electroencephalogram. There was no recurrence on the third day after adding lacosamide, and there was no attack after 5 months of follow-up. No obvious adverse reactions were found during follow-up.Conclusions:Sodium channel related epileptic encephalopathy often starts early, has frequent seizures, and can be accompanied by backward psychomotor development at the same time. The slow sodium channel blocker lacosamide has good efficacy and safety in the treatment of sodium channel-related epilepsy with SCN2A gene mutation or combined SCN1A gene mutation.

Objective: The etiology of schizophrenia is unknown and is associated with abnormal spontaneous brain activity. There are no consistent results regarding the change in spontaneous brain activity of people with schizophrenia. In this study, we determined the specific changes in the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) in patients with drug-naïve first-episode schizophrenia (Dn-FES). Methods: A comprehensive search of databases such as PubMed, Web of Science, and Embase was conducted to find articles on resting-state functional magnetic resonance imaging using ALFF/fALFF and ReHo in schizophrenia patients compared to healthy controls (HCs) and then, anatomical/activation likelihood estimation was performed. Results: Eighteen eligible studies were included in this meta-analysis. Compared to the spontaneous brain activity of HCs, we found changes in spontaneous brain activity in Dn-FES based on these two methods, mainly including the frontal lobe, putamen, lateral globus pallidus, insula, cerebellum, and posterior cingulate cortex. Conclusion We found that widespread abnormalities of spontaneous brain activity occur in the early stages of the onset of schizophrenia and may provide a reference for the early intervention of schizophrenia.

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.

Objective To investigate the effect of compound Fufangteng mixture-containing serum on the proliferation of bone marrow mesenchymal stem cell (BMSC) and its mechanism. Methods Rat BMSC were isolated, cultured and purified in vitro by direct adherence method. Cell morphology was observed. Surface markers were identified by flow cytometry. The rats were treated with compound Fufangteng mixture at a dose of 3 mL/(kg·d) by gavage for 14 d, and then the drug-containing serum was collected. BMSC were divided into the blank control group, drug-containing serum group, Notch1 small interfering ribonucleic acid (siRNA) group and Notch1 siRNA+drug-containing serum group. The proliferation rate of BMSC was detected and the relative expression levels of Notch1 signaling pathway-associated messenger ribonucleic acid (mRNA) and proteins were measured in each group. Results Microscopic observation showed that the first generation BMSC were seen in the long spindle shape, and grown in the parallel or spiral pattern. The third generation BMSC positively expressed CD90 and CD44, whereas were negative for CD45. Compared with the blank control group, the proliferation rate of BMSC in the drug-containing serum group and Notch1 siRNA+ drug-containing serum group was significantly increased, whereas that of BMSC was significantly decreased in the Notch1 siRNA group (all P < 0.05). Compared with the Notch1 siRNA group, the proliferation rate of BMSC was significantly increased in the Notch1 siRNA+drug-containing serum group (P < 0.05). Compared with the blank control group, the relative expression levels of Hey1 and Delta-like ligand (DLL)1 mRNA and proteins were significantly up-regulated in the drug-containing serum group, whereas those were significantly down-regulated in the Notch1 siRNA group and Notch1 siRNA+drug-containing serum group (all P < 0.05). Compared with the Notch1 siRNA group, the relative expression levels of Hey1 and DLL1 mRNA and proteins were significantly up-regulated in the Notch1 siRNA+drug-containing serum group (all P < 0.05). Conclusions Compound Fufangteng mixture-containing serum may promote the proliferation of rat BMSC, and its mechanism is probably associated with the activation of Notch1 signaling pathway.

【Objective】 To study the annual financial expenditure in blood stations with different scales, and to establish the regression equation between blood collection units and total expenditure. 【Methods】 The annual total expenditure, the per capita cost of serving population, as well as the collection units of whole blood and apheresis platelet of 24 blood stations were collected. The financial expenditure required for collecting 10 000U blood was calculated.The statistical analysis was carried out with SPSS statistical software. 【Results】 From 2017 to 2020, the total annual financial expenditure of 24 blood stations showed an upward trend. The total expenditure among blood stations was different. The per capita cost of servicing population in the areas where the 24 blood stations were located had been increasing year by year. The 24 blood stations were divided into two grades according to the blood collection volume as 50 000 U, and the relationship equation between the blood collection volume and the annual total expenditure had been established. After testing, each equation was effective(P<0.05); There was no difference in the financial expenditure required for collecting 10 000U blood among blood stations with different scales. 【Conclusion】 From 2017 to 2020, the blood stations with an annual collection volume more than 50 000 U demonstrated a higher financial expenditure and the per capita cost of serving population than those <50 000 U. The blood collection volume of blood stations is significantly correlated with the annual total expenditure and the per capita cost of serving population.

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–pro-tein interaction networks can reveal cellular pathways critical to viral replication and disease patho-genesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as crit-ical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for fur-ther studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/μL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.
Acquired Immunodeficiency Syndrome ; Humans ; Lymphoma, Non-Hodgkin ; Neoplasm Staging ; Nomograms ; Prognosis ; Retrospective Studies