Our previous studies have shown that calcitonin gene-related peptide (CGRP) exerts protective effects on the acute lung injury induced by oxidative stress. This study was aimed to investigate whether autophagy was involved in the protection of CGRP against oxidative stress-induced lung injury in neonatal rats. Newborn Sprague-Dawley (SD) rats were randomly divided into five groups: Control group, oxidative stress model group (Model group), Model + CGRP group, Model + CGRP + Rapamycin (an autophagy agonist) group, and Model + CGRP + LY294002 (an autophagy inhibitor) group. The model of hyperoxia-induced lung injury was established by continuous inhalation of oxygen (FiO₂ = 90%-95%) for 14 days in neonatal SD rats. Pathological changes of lung tissue were observed by hematoxylin and eosin (HE) staining, and mean linear intercept (MLI) was measured. The quantitative changes of autophagic vesicles (AV) in type II alveolar epithelial cells (AECII) were measured under the transmission electron microscope. The protein expressions of Caspase-3, Bcl-2, mTOR, and Beclin-1 in lung tissue lysates were detected by Western blot. The results showed that, compared to the Model group at the same time point, the number of AV in AECII and the expression level of Beclin-1 protein of the lung tissue were increased, while the expression level of mTOR protein was decreased, with alleviated pathological changes, reduced MLI value and Caspase-3 protein expression level, increased Bcl-2 protein expression level in the lung tissue of Model + CGRP group. In addition, we found that the protective effect of CGRP on hyperoxia-induced lung injury could be enhanced by autophagy activator Rapamycin and abolished by autophagy inhibitor LY294002. Together, these findings indicate that CGRP could attenuate hyperoxia-induced lung injury in neonatal rats by enhancing autophagy.
Acute Lung Injury/pathology* ; Animals ; Animals, Newborn ; Autophagy ; Calcitonin/metabolism* ; Calcitonin Gene-Related Peptide/metabolism* ; Caspase 3/metabolism* ; Hyperoxia/pathology* ; Lung/pathology* ; Lung Injury/prevention & control* ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; Sirolimus/pharmacology*

Objective : To investigate the protective effect of mitochondria-derived peptide MOTS-c on myocardial ischemia reperfusion injury (MIRI) in rats and elucidate its mechanism． Methods : The SD rats were randomly di- vided into sham group，MIRI group，MOTS-c group and MOTS-c + PGC-1α inhibitor SR-18292 group (MOTS-c + SR-18292) ，with 10 rats in each group． The MIRI model was established by ligating the anterior descending branch of the coronary artery MOTS-c peptide ( 1 mg / kg) ，SR-18292 (20 mg / kg) and equal volume concentration of 1% dimethyl sulfoxide were administered via tail vein at 1 h before operation and immediately after operation．At 24 h after surgery，TTC staining was used to observe myocardial infarction size．HE staining was used to observe the pathological changes of myocardial tissue．TUNEL staining was used to detect myocardial apoptosis．ELISA and biochemical kits were used to measure the levels of myocardial injury markers and oxidation indicators in serum of each group．The relative copy number of mtDNA in myocardial tissues was detected by qRT-PCR. The mitochondri- al biosynthesis-related protein expression levels in myocardial tissues were detected by Western blot. Results: Compared with sham group，MIRI group had serious myocardial injury，myocardial infarction size and increased ap- optosis level (P＜0. 05) ．The mtDNA relative copy number in myocardial tissue decreased (P＜0. 05) ．The con- tents of CK-MB ，LDH ，cTnI in serum and MDA in myocardial tissue increased (P ＜0. 05 ) ． SOD content and PGC-1α , NRF-1 and TFAM protein expression levels in myocardial tissue decreased (P＜0. 05) ．Compared with MIRI group，myocardial injury in MOTS-c group was significantly improved，myocardial infarction size and apopto- sis level decreased (P＜0. 05) ．The mtDNA relative copy number in myocardial tissue increased (P＜0. 05) ．The contents of CK-MB，LDH，cTnI in serum and MDA in myocardial tissue decreased (P＜0. 05) ．The SOD content and the expression levels of PGC-1α , NRF-1 and TFAM in myocardial tissue increased (P ＜0. 05 ) ． Compared with MOTS-c group ，the myocardial infarction size and apoptosis level of rats in MOTS-c + SR-18292 group in- creased (P＜0. 05) ．The mtDNA relative copy number in myocardial tissue decreased (P＜0. 05) ．The contents of CK-MB，LDH，cTnI in serum and MDA in myocardial tissue increased (P＜0. 05) ．SOD content and PGC-1α , NRF-1 and TFAM protein expression levels in myocardial tissue decreased ( P ＜0. 05 ) ． Conclusion MOTS-c peptide can improve myocardial injury in MIRI rats by promoting mitochondrial biosynthesis and inhibiting cardio- myocyte apoptosis，and its mechanism may be related to up-regulation of PGC-1α expression.

The purpose of this study was to explore the effect and mechanism of dihydromyricetin (DHM) on Parkinson's disease (PD)-like lesions in type 2 diabetes mellitus (T2DM) rats. The T2DM model was established by feeding Sprague Dawley (SD) rats with high-fat diet and intraperitoneal injection of streptozocin (STZ). The rats were intragastrically administered with DHM (125 or 250 mg/kg per day) for 24 weeks. The motor ability of the rats was measured by balance beam experiment, the changes of dopaminergic (DA) neurons and the expression of autophagy initiation related protein ULK1 in the midbrains of the rats were detected by immunohistochemistry, and the protein expression levels of α-synuclein (α-syn), tyrosine hydroxylase (TH), as well as AMPK activation level, in the midbrains of the rats were detected by Western blot. The results showed that, compared with normal control, the rats with long-term T2DM exhibited motor dysfunction, increased α-syn aggregation, down-regulated TH protein expression, decreased number of DA neurons, declined activation level of AMPK, and significantly down-regulated ULK1 expression in the midbrain. DHM (250 mg/kg per day) treatment for 24 weeks significantly improved the above PD-like lesions, increased AMPK activity, and up-regulated ULK1 protein expression in T2DM rats. These results suggest that DHM may improve PD-like lesions in T2DM rats by activating AMPK/ULK1 pathway.
Rats ; Animals ; Parkinson Disease ; Rats, Sprague-Dawley ; AMP-Activated Protein Kinases ; Diabetes Mellitus, Type 2 ; Autophagy-Related Protein-1 Homolog

Chloroquine is a quinine derivative which is synthesized by German scholars in 1934. In addition to its anti-malaria, treatment of systemic lupus erythematosus and immunomodulatory effects, chloroquine is also found valuable in broad-spectrum antiviral treatment. Clinical trials have confirmed that chloroquine has a good effect on acquired immunodeficiency syndrome. In 2019, there were many patients infected with novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2). Preliminary clinical trials showed that chloroquine had obvious curative effect on patients with SARS-CoV-2. We summarize the effects of chloroquine to different viruses, explain its mechanism, and compare the results of its experiments in vitro and in vivo. The antiviral effect of chloroquine in vivo and in vitro are not consistent, which may be related to the model of animal, dosage and distribution of chloroquine in vivo, and the design of clinical research.

Biodegradable vascular stents have better biocompatibility than drug-eluting stents. The blood vessels are rebuilt and degraded after normal physiological functions are restored. Due to it will not stay in the body for a long time and the patients don't need taking anti-rejection drugs all the time, it becomes the focus of attention in the treatment of coronary heart disease. This article introduced the development history of biodegradable stents and reviewed the research status of several different materials of vascular stents (animals or humans)
Absorbable Implants ; Animals ; Drug-Eluting Stents ; Humans ; Stents

自噬是细胞内一种高度保守的生理过程，可通过溶酶体系统降解过量或受损的细胞器、有毒的蛋白聚集体和病原体等。最新研究表明，海马钙素样1（HPCAL1）可作为特异性自噬受体和铁死亡的正调节因子。HPCAL1可选择性降解钙粘素2（CDH2），加速脂质过氧化，促进癌细胞铁死亡。iHPCAL1是抑制HPCAL1的小分子化合物，可抑制Erastin诱导的肿瘤细胞铁死亡。此外，它还可以抑制铁死亡诱导的急性胰腺炎。本文通过对HPCAL1在铁死亡中的具体作用机制进行概述，为HPCAL1作为铁死亡相关疾病的潜在治疗靶点提供新思路和理论依据。
Ferroptosis ; Cell Line, Tumor ; Autophagy

OBJECTIVE：To investigate the pharmaceutical ca re for a child with refractory Stenotrophomonas maltophilia sepsis by clinical pharmacists ，and to provide reference for the treatment of children with this disease. METHODS ：Clinical pharmacist participated in drug therapy for a child with refractory S. maltophilia sepsis. Based on the pathophysiological characteristics of the child and the PK/PD characteristics of the antimicrobials ，clinical pharmacists suggested that the anti-infection regimen should be adjusted as cefoperazone sodium and sulbactam sodium 160 mg/（kg·d），every 8 hours combined with levofloxacin 10 mg/kg， every 12 hours. For clinical manifestations of severe inflammatory reaction ， the clinical pharmacist suggested receiving methylprednisolone sodium succinate 1 mg/kg additionally ，every 12 hours，for anti-inflammatory adjuvant therapy. At the same time， clinical pharmacist provided individualized pharmaceutical care （including the detection of blood concentration of cefoperazone sodium and sulbactam sodium ，the detection of ADR and medication education of oxygen atomization ）during the treatment，and followed up the child for one year. RESULTS ：The doctors adopted the suggestions of clinical pharmacists. The sepsis was controlled ，the child ’s condition were improved and then discharged. During the follow-up ，the child did not suffered from ADR ，such as cartilage and joint injury. CONCLUSIONS ：Hypoimmunity，long stay in intensive care unit ，endotracheal intubation and malignant tumor are the high risk factors of S. maltophilia infection. The monitoring of therapeutic drugs of cefoperazone sodium and sulbactam sodium is very necessary in the treatment of severe infection in children. After weighing the advantages and disadvantages and meeting certain conditions ，children can use quinolones for anti-infection ；based on the effective anti-infection treatment ，low-dose glucocorticoid can reduce the systemic inflammatory respense in patients with sepsis.

Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg

OBJECTIVE: To probe the correlation between the postmortem interval (PMI) and the DNA degradation of costicartilage and dental pulp cells in human being after death, and to seek a new method for estimating PMI. METHODS: The image cytometry was used to measure the DNA degradation under different ambient temperatures (30-35 degrees C, 15-20 degrees C) in 0-15 days after death. RESULTS: The average DNA content of two kinds of tissue was degradated with the prolongation of PMI. But there was a plateau period of 0-4 days for dental pulp cells of human being in 15-20 degrees C. There was a high negative correlativity P<0.01 between the average DNA content and PMI. CONCLUSION PMI could be estimated accurately according to the DNA degradation of costicartilage and dental pulp cells in human being after death.
Adolescent ; Adult ; Autopsy ; Cartilage/metabolism* ; DNA/metabolism* ; Dental Pulp/cytology* ; Female ; Forensic Pathology/methods* ; Humans ; Image Processing, Computer-Assisted/methods* ; Male ; Middle Aged ; Postmortem Changes ; Ribs/metabolism* ; Temperature ; Time Factors ; Young Adult

ObjectiveTo investigate the role and mechanism of hyodeoxycholic acid （HDCA） in the progression of metabolic associated fatty liver disease （MAFLD）， and to provide a new theoretical basis for further clarifying the pathogenesis of MAFLD. MethodsL02 hepatocytes were used as experimental cells， and palmitic acid was used to induce steatosis in L02 cells. The farnesoid X receptor （FXR） siRNA interference chain technique was used to construct a hepatocyte cell line with low FXR expression. CCK8 assay was used to observe the effect of HDCA on L02 steatosis hepatocytes at different concentrations （0， 100， 200， 300， and 400 μmol/L） and time points （12， 24， 36， and 48 hours）. The method of qRT-PCR was used to measure the mRNA expression levels of FXR， proliferating cell nuclear antigen （PCNA）， Cyclin D1， phosphatidylinositol 3-kinase （PI3K）， and protein kinase-B （AKT）， and Western blot was used to measure the protein expression levels of FXR， Cyclin D1， PCNA， PI3K， phosphorylated PI3K （p-PI3K）， AKT， and phosphorylated （p-AKT）. A one-way analysis of variance was used for comparison of normally distributed continuous data with homogeneity of variance between multiple groups， and the Tukey HSD test was used for further comparison between two groups； the Welch analysis of variance was used for comparison of normally distributed continuous data with heterogeneity of variance between multiple groups， and the Games-Howell test was used for further comparison between two groups. The independent-samples t test was used for comparison between two groups. ResultsCCK8 assay showed a significant reduction in the viability of L02 cells and steatosis hepatocytes treated by 300 μmol/L HDCA （P<0.05）， and qRT-PCR showed a significant increase in the mRNA expression level of FXR and significant reductions in the mRNA expression levels of PCNA， Cyclin D1， PI3K， and AKT （all P<0.05）. Western blot showed a significant increase in the protein expression level of FRX （P<0.05）， and after interference of FXR expression in L02 cells， there were significant increases in the protein expression levels of PCNA， PI3K， p-PI3K， AKT， and p-AKT （all P<0.05）. ConclusionHDCA inhibits the PI3K/AKT signaling pathway by upregulating FXR expression， thereby inducing a reduction in the viability of steatosis hepatocytes.