ObjectiveTo investigate the effects of autophagy on exocrine function of pancreas in rats with acute sepsis, and to determine whether the mitochondrial coenzyme Q (Mito Q) can prevent exocrine dysfunction of pancreas mediated by autophagy.Methods ExperimentⅠ: 30 Sprague-Dawley (SD) rats were randomly divided into three groups, with 10 rats in each group. All the rats were given lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally, and Wortmannin (2 mg/kg), the specific inhibitor of autophagy (LPS+ Wortmannin group), Mito Q (6.5μmol/kg, LPS+Mito Q group), or the same volume of normal saline (LPS group) was respectively injected via the tail vein 1 hour later. Survival rate was assessed within 12 hours after LPS injection. ExperimentⅡ: another 100 male SD rats were randomly divided into ten groups with 10 rats in each group: namely control 4, 6 and 12 hours groups, LPS 4, 6 and 12 hours groups, and LPS+ Wortmannin 4 hours group, Wortmannin 4 hours group, LPS+ Mito Q 6 hours group, and Mito Q 6 hours group. The protocols of model reproduction and drug administration were the same as in the experimentⅠ. Blood samples were collected at each time point, and the amylase content was determined with the velocity method. The levels of reactive oxygen species (ROS) in the pancreases were measured with enzyme-linked immunosorbent assay (ELISA). The expression of the autophagy-related protein LC3 was determined with Western Blot. The pathological changes in the pancreas were observed with microscopy.Results① The survival time in the LPS+ Wortmannin group was significantly shorter than that in the LPS group (hours: 7.50±0.64 vs. 11.90±0.13,χ2= 19.847,P= 0.001). There was no significant difference in the survival time between LPS+ Mito Q and LPS groups (hours: 11.60±0.24 vs. 11.90±0.13,χ2= 1.055,P= 0.137).② The serum amylase in the LPS 6 hours, LPS+ Wortmannin 4 hours, and LPS+ Mito Q 6 hours groups were significantly higher than those in the control group at the same time points (U/L:2 881.00±550.12 vs. 2 099.20±249.57, 3 672.00±779.24 vs. 2 081.36±245.18, 2 975.20±687.03 vs. 2 099.20± 249.57, allP< 0.05), and were significantly lowered in LPS 12 hours group (U/L: 794.00±218.71 vs. 2 086.80±261.75, P< 0.01). The pancreatic ROS in the LPS 6 hours and 12 hours groups, LPS+ Wortmannin 4 hours group, and LPS+Mito Q 6 hours group were significantly higher than those of the control group at the same time points (kU/L: 3.18±1.06 vs. 1.78±0.37, 3.63±1.08 vs. 1.85±0.41, 3.14±0.98 vs. 1.65±0.34, 3.17±1.03 vs. 1.78±0.37, allP< 0.05). The serum amylase and pancreatic ROS in LPS+ Wortmannin 4 hours group were significantly higher than those of the LPS group at the same time points (U/L: 3 672.00±779.24 vs. 2 432.20±442.85, kU/L: 3.14±0.98 vs. 1.87±0.42, both P< 0.05), but there were no differences in above two parameters between LPS+ Mito Q 6 hours group and LPS group (U/L: 2 975.20±687.03 vs. 2 881.00±550.12, kU/L: 3.17±1.03 vs. 3.18±1.06, bothP> 0.05). Light microscopy showed that obvious pathological changes were found in the pancreas in the LPS 6 hours and 12 hours groups, LPS+Wortmannin 4 hours group, and LPS+ Mito Q 6 hours group. Electron microscopy showed that the number of autophagic vacuoles increased 6 hours after LPS administration. There was no difference at any time point in the number of autophagic vacuoles between LPS+ Mito Q 6 hours group and LPS 6 hours group, and the autophagic vacuoles were not found after Wortmannin intervention. It was demonstrated by Western Blot that the levels of LC3 protein in the LPS 6 hours and 12 hours groups, and LPS+ Mito Q 6 hours group were significantly higher than those of the control group at the same time points (A value: 0.34±0.02 vs. 0.17±0.02, 0.37±0.03 vs. 0.18±0.04, 0.36±0.02 vs. 0.17±0.02, allP< 0.05), but there were no differences between LPS 12 hours group or LPS+ Mito Q 6 hours group and LPS 6 hours group (bothP> 0.05).Conclusions Autophagy prevents exocrine dysfunction of pancreas in septic rats, and the autophagic capacity or autophagosome-formation rate may determine the development of exocrine pancreatic dysfunction. The mitochondria-targeted antioxidant Mito Q does not prevent exocrine dysfunction of pancreas.

Objective To investigate the effects of autophagy on cardiac function and to determine whether the mitochondrial coenzyme Q (MitoQ) prevents cardiac dysfunction,mediated by autophagy,in rats with acute sepsis.Methods Forty-five Sprague Dawley (SD) rats were randomly divided into 9 groups (n =5,each group):control group,4 h lipopolysaccharide(LPS) group,6 h LPS group,12 h LPS group,4 h LPS + Wortmannin group,4 h LPS + MitoQ group,6 h LPS + MitoQ group,MitoQ group and Wortmannin group.Rats in LPS + Wortmannin group and LPS + MitoQ group were intraperitoneally given LPS(10 mg/kg) and followed by an injection of Wortmannin(2 mg/kg) and MitoQ (6.5 μmol/kg) via tail vein 1 hour later,respectively.Rats in each group were given the same amount of normal sodium in addition to different intervention drugs.The cardiac function parameters were measured by a BL-420E + biosignal collection system.Blood samples from abdominal aorta were taken at each time point,and creatine kinase MB isoenzyme (CK-MB) content was detected by using the velocity method.The content of reactive oxygen species (ROS) in isolated myocardial tissues in rats was measured by enzyme-linked immunoadsorbent assay(ELISA).The protein expression of microtubule-associated protein 1 light chain 3 (LC3) was detected by Western blot method.The pathological changes of myocardial tissue were observed by light and electronic microscopy.Results Compared with the control group,the left ventricular systolic pressure(LVSP),the rate of the rise in left ventricular pressure (± dp/dt max) were significantly decreased in 6 h LPS group,6 h LPS + MitoQ group and 4 h LPS + Wortmannin group(P ＜0.05),left ventricular end-diastolic pressure(LVEDP) was significantly increased in these 3 groups(P ＜0.05).The contents of CKMB and ROS in 6 h LPS group,6 h LPS =MitoQ group and 4 h LPS + Wortmannin group were higher than those in the control group(P ＜ 0.05).Electron microscopy showed that the number of autophagic vacuoles increased 6 h after LPS was administered,but did not increase significantly thereafter to 12 h.There was no difference at any time point in the number of autophagic vacuoles in the group given MitoQ and LPS.Immunoblotting demonstrated that the levels of LC3Ⅱ protein in the LPS 6 h group and LPS + MitoQ 6 h group were higher than those in the control group(P ＜0.05),but there was no difference between the LPS 12 h and LPS 6 h groups (P ＞ 0.05).Conclusions The mitochondria-targeted antioxidant MitoQ does not prevent cardiac dysfunction.However,autophagy prevents cardiac dysfunction,and the autophagic capacity or autophagosome-formation rate may determine whether cardiac dysfunction develops.

The evaluation tools were developed based on the theory of validity,the development process and results of the Manual of Home-Based Rehabilitation Mode for Stroke Patients were evaluated by a panel of experts,and the opinions and suggestions for improvement were collected from the evaluation experts.The results showed that the average score for development process and results of the manual were ＞4 points in structural validity,content validity and surface validity,indicating that the manual was of high quality,and the development of the manual was scientific and the results were practical.The manual may provide the guidance for the home-based rehabilitation in community.At the same time,this study has enriched the reviewing tools and evaluation method of manuals,and provided reference for the peers.

OBJECTIVETo observe the effect of single administration of mercury- containing preparation Jiuyi Dan (calcined gypsum-Shengdan 9: 1) and Shengdan on acute toxicity of rabbits, in order to assess the safety of tested drugs.

METHODThe rabbits were randomly divided into 4 groups: the calcined gypsum group (excipient control), the Jiuyi Dan group, the 90 mg Shengdan group and the 180 mg Shengdan group. After 270 mg of calcined gypsum, 300 mg of Jiuyi Dan, 90 mg of Shengdan, and 180 mg of Shengdan were used on the surface of wounds (5 cm x 5 cm) on two sides of rabbit back for 5 h, the surfaces of wound were washed by water. The bloods were taken from the rabbit hearts before and after the drug administration for 24 h, 72 h, 7 d and 14 d for determining Hg level in blood and liver & kidney function indicators (ALT, AST, CREAT, and BUN). The rabbits were dissected after the drugs treatment for 14 d, and pathological tests were made for their livers and kidneys.

RESULTCompared with the calcined gypsum group, the 90 mg Shengdan group and the 180 mg Shengdan group showed significant increase (P < 0.01 or P < 0.05), as evidenced by increase in CREAT for 24 h and 72 h and increase in BUN for 24 h and on 7 d. AST is significantly increased as well (P < 0.01) for 24 h and 72 h compared to that of the group before drug treatment. The Hg level in blood was significantly enhanced (P < 0.01) after the rabbits were administrated with drugs for 24 h to 72 h. The pathological changes in livers and kidneys of rabbits were observed in the two doses of Shengdan treatment groups.

CONCLUSIONThe Hg blood levels were increased significantly in an obvious dose-effect relationship in all drugs treatment groups. Liver & kidney function indicators were influenced by Shengdan treatment to some extent. Meanwhile, pathological changes in rabbit livers and kidneys were also caused by Shengdan, while Jiuyi Dan has no significantly effect on livers and kidneys.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Rabbits ; Random Allocation ; Skin ; drug effects ; injuries ; Time Factors ; Toxicity Tests, Acute

OBJECTIVETo observe the changes of the blood and urine mercury (Hg) levels and liver & kidney functions of rabbits after administration of Jiuyi Dan (calcined gypsum-Sheng Dan 9: 1) for 1 month and the recovery of rabbits after the drug withdrawal.

METHODThe rabbits were randomly divided into 2 groups: the calcined gypsum group and the Jiuyi Dan group. After 36 mg of calcined gypsum and 40 mg of Jiuyi Dan were used on the surface of wound (5 cm x 5 cm) on one side of rabbit back for 4 h, the surfaces of wound were washed by saline. The bloods were taken from the rabbit hearts before and after the drug administration for 14 and 28 days, and after the drug withdrawal for 7, 40, 71, and 92 days for determining Hg level in blood, and liver & kidney function indicators (ALT, AST, CREAT and BUN). The Hg level in urine collected from bladders was examined while rabbits were dissected after the drug withdrawal for 1, 40, 71, and 92 days.

RESULTThe Hg level in blood was significantly increased (P < 0.01) after the rabbits were administrated with drugs for 14 and 28 days and after the drug treatment was stopped for 7 and 40 days. The Hg level in urine was significantly enhanced after the drug withdrawal for 1, 40, 71 days. However, the liver & kidney indicators were not influenced.

CONCLUSIONThe Hg level in rabbit blood and urine was significantly increased after the consecutive administration of double-dose Jiuyi Dan for 1 month. However, the blood Hg level and urine Hg level recover after the drug withdrawal for 71 days and 3 months, respectively. The liver & kidney indicators do not significantly change with the dose.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mercury ; blood ; metabolism ; urine ; Rabbits ; Random Allocation ; Skin ; drug effects ; injuries ; Time Factors

The amplifier is easy to saturation because of polarization voltage in ambulatory ECG acquisition. The traditional way is using analog high-pass filter to eliminate, but the output tends to have a residue. If upgrading high-pass filter cutoff frequency, it will lead to low frequency distortion of ECG signals. In this paper, a Savitzky-Golay (SG) smoothing filter has been designed by combining the single edge point and the polynomial order , which can fit the polarization voltage components of ECG signals, filter useful components and get drift-free ECG signals by using the subtraction algorithm. The results of ECG filtering experiment verify the feasibility of the SG smoothing filter, and show the filtered ECG signal without any losses of useful components.
Algorithms ; Amplifiers, Electronic ; Electrocardiography, Ambulatory ; methods ; Humans ; Signal Processing, Computer-Assisted

Objective:This study examines the application of echocardiography in the prenatal diagnosis of copy number variation (CNV) associated with fetal congenital heart disease (CHD).Methods:A retrospective analysis was conducted on 447 singleton pregnancies from Quanzhou Maternal and Child Care Hospital (Quanzhou Children's Hospital) from January 2019 to August 2022. These individuals underwent echocardiographic assessments suggestive of fetal CHD and subsequently received invasive prenatal diagnoses. Comprehensive karyotype analysis and chromosome microarray analysis (CMA) were performed for each case. The discrepancies in the chromosomal abnormality detection were analyzed between the results produced by CMA and karyotype analysis. Furthermore, differences in the detection of pathogenic copy number variation (pCNV) between the two methods in CHD cases with diverse cardiac phenotypes, including the presence or absence of extracardiac structural malformations, the type, and quantity of cardiac structural anomalies, were explored. Statistical analysis was conducted using the Chi-square test. Results:Compared with conventional karyotype analysis, CMA demonstrated a higher detection rate of fetal chromosomal abnormalities [10.5% (47/447) vs. 20.6% (92/447), χ 2=161.56, P<0.001]. In terms of distinct cardiac phenotypes, CHD cases with extracardiac structural anomalies displayed an escalated pCNV detection rate in comparison to isolated CHD cases [11.4% (45/394) vs. 32.1% (17/53), χ 2=16.68, P<0.001]. Within the cardiac structural anomaly subgroups, increased pCNV detection rates were observed in the septal defect subgroup, conotruncal malformation subgroup, and left ventricular malformation subgroup [18.4%(29/158), 25.9%(7/27), and 25.0%(7/28) vs. 7.6%(16/210); χ 2=9.15, 9.68, and 8.55, respectively, all P<0.05]. The CMA-identified pCNV correlated with CHD included 22q11.2 deletions/duplications in eight cases, 4p16.3 deletions in two cases, 11q23.3 microduplications in two cases, 1q21.1 microdeletions/microduplications in two cases, 4q28.3 microduplications in one case, and 10p15.3 microdeletions in one case. Conclusions:CMA technology exhibited an enhanced ability to detect pCNV in fetuses with CHD. Echocardiography can guide targeted CMA screening, thereby facilitating prenatal genetic assessment of CHD.

MicroRNA is a class of short-chain non-coding RNA that regulates gene expression at post-transcriptional level.It can participate in the pathophysiology processes of tumor regulation,neurodegenerative disease,and cardiovascular disease.Recent studies have shown that microRNA can play a reguhtory role in ischemic brain damage through autophagy.This article reviews the effect of microRNA on autophagy after cerebral ischamia and its possible mechanisms.

To explore the role of forkhead box protein O1 (FOXO1) in the progression of glioblastoma multiforme (GBM) and related drug resistance, we deciphered the roles of FOXO1 and miR-506 in proliferation, apoptosis, migration, invasion, autophagy, and temozolomide (TMZ) sensitivity in the U251 cell line using in vitro and in vivo experiments. Cell viability was tested by a cell counting kit-8 (CCK8) kit; migration and invasion were checked by the scratching assay; apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. The construction of plasmids and dual-luciferase reporter experiment were carried out to find the interaction site between FOXO1 and miR-506. Immunohistochemistry was done to check the protein level in tumors after the in vivo experiment. We found that the FOXO1-miR-506 axis suppresses GBM cell invasion and migration and promotes GBM chemosensitivity to TMZ, which was mediated by autophagy. FOXO1 upregulates miR-506 by binding to its promoter to enhance transcriptional activation. MiR-506 could downregulate E26 transformation-specific 1 (ETS1) expression by targeting its 3'-untranslated region (UTR). Interestingly, ETS1 promoted FOXO1 translocation from the nucleus to the cytosol and further suppressed the FOXO1-miR-506 axis in GBM cells. Consistently, both miR-506 inhibition and ETS1 overexpression could rescue FOXO1 overactivation-mediated TMZ chemosensitivity in mouse models. Our study demonstrated a negative feedback loop of FOXO1/miR-506/ETS1/FOXO1 in GBM in regulating invasiveness and chemosensitivity. Thus, the above axis might be a promising therapeutic target for GBM.
Animals ; Mice ; Brain Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; Feedback ; Gene Expression Regulation, Neoplastic ; Glioblastoma/metabolism* ; MicroRNAs/metabolism* ; Temozolomide/therapeutic use* ; Humans ; Forkhead Box Protein O1/metabolism*

Specific pathogen-free (SPF) chickens are widely used in the research of avian diseases and vaccines. Vertically transmissible diseases are transmitted to chickens through vertical transmission, seriously affecting their survival rate, increasing production costs, and causing significant economic losses to the poultry industry, while severely impacting the breeding and use of SPF chickens. Therefore, it is crucial for researchers and managers to enhance their understanding of vertically transmissible pathogens in chickens and to develop effective monitoring measures. Quality monitoring is an important part of ensuring the quality of SPF chickens, with pathogen detection being the primary step. Based on this, it is necessary to cultivate qualified SPF chickens through purification methods and biosecurity measures. This paper reviews the major vertically transmissible pathogens in chickens, including viral pathogens, bacterial pathogens and mycoplasmas, as well as their detection methods. This study compares the differences in microbiological testing items and methods for SPF chickens between the U.S. corporate standard and the Chinese national standard. Analysis of the results shows that in both standards, vertically transmissible pathogens such as Escherichia coli, Proteus mirabilis, Salmonella, and avian leukosis are not included in the microbiological testing items for SPF chickens. Instead, these pathogens are characterized by mixed infections, and outbreaks can seriously affect flock health. To produce higher-quality SPF chickens, it is necessary to include these pathogens in the mandatory testing items. The aim of this paper is to help readers understand the relevant standards for microbiological monitoring of SPF chickens, the hazards of vertically transmissible pathogens, and prevention and control strategies, so as to provide a reference for the detection and purification of pathogens in SPF chickens.