OBJECTIVE: To observe the effects of Tongdu Tiaoshen acupuncture (for unblocking the obstruction in the governor vessel and regulating the spirit) on depression-like behavior and the hippocampal Endophilin A1/reactive oxygen species (ROS) pathway in the chronic unpredictable mild stress (CUMS) model rats, and explore the mechanism of this therapy for depression. METHODS: Forty-eight male SD rats of SPF grade were randomly divided into a normal group (n=12) and a modeling group (n=36). In the modeling group, CUMS was performed to establish depression model. The successfully-modeled rats were randomized into a model group, a Tongdu Tiaoshen acupuncture group (referred to as the acupuncture group), and a fluoxetine group, with 12 rats in each group. In the acupuncture group, "Baihui" (GV20), "Shenting" (GV24), "Shuigou" (GV26) and "Dazhui" (GV14) were stimulated with acupuncture. This intervention measure was delivered once a day, continuously for 6 days; it was discontinued on day 7 and was completed in 28 days. In the fluoxetine group, intragastric administration was done with fluoxetine solution (2.1 mg/kg), once a day, and for 28 consecutive days. Before and after modeling, and after intervention completion, the body mass, sucrose preference rate and the total distance of movement and the boxes of horizontal crossing in the open field experiment were observed in each group. After intervention, using HE staining, the hippocampal neuron morphology was observed; using Nissl staining, the hippocampal Nissl body number was counted. The hippocampal mitochondria was observed under transmission electron microscopy. The average fluorescence intensity of ROS in hippocampal was determined using flow cytometry. With Western blot method, the protein expression of Endophilin A1, growth associated protein 43 (GAP-43), and brain-derived neurotrophic factor (BDNF) in hippocampal was detected; and with RT-qPCR method, the mRNA expression of Endophilin A1, GAP-43, and BDNF was recorded. Using the immunofluorescence, the average fluorescence intensity of Endophilin A1, GAP-43, and BDNF in hippocampal tissue was determined. RESULTS: Compared with the normal group, in the model group, the body mass, sucrose preference rate, and the total distance of movement and the boxes of horizontal crossing in the open field experiment decreased (P<0.01); the hippocampal neuronal structure was unclear, the matrix was relatively loose, and the number of Nissl body decreased (P<0.01); mitochondrial structure was disarranged, the outer membrane was ruptured, mitochondrial cristae was irregular or missed; the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue increased (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and its average fluorescence intensity decreased (P<0.01). Compared with the model group, the acupuncture group and the fluoxetine group showed the increase in body mass, sucrose preference rate, the total distance of movement and the boxes of horizontal crossing in the open field experiment (P<0.05, P<0.01); the hippocampal neuronal structure became relatively clear, the matrix was relatively dense, and the number of Nissl body was elevated (P<0.01); mitochondrial structure got normal and disarranged slightly, the average fluorescence intensity of ROS in hippocampal tissue, the protein and mRNA expression and the average fluorescence intensity of Endophilin A1 in hippocampal tissue were reduced (P<0.01), while the protein and mRNA expression of GAP-43 and BDNF and the average fluorescence intensity rose (P<0.01, P<0.05). Compared with the fluoxetine group, the acupuncture group presented the increase in the average fluorescence intensity of ROS, the protein expression and the average fluorescence intensity of Endophilin A1, the protein expression of GAP-43 and the mRNA expression of BDNF (P<0.01, P<0.05), and the decrease of the protein expression and the average fluorescence intensity of BDNF, the mRNA expression of Endophilin A1, and the average fluorescence intensity of GAP-43 (P<0.01, P<0.05). CONCLUSION Tongdu tiaoshen acupuncture alleviates depression-like behaviors in CUMS model rats and protects hippocampal neurons, which may be related to suppressing Endophilin A1/ROS signaling pathway and attenuating oxidative stress reactions.
Animals ; Male ; Hippocampus/metabolism* ; Acupuncture Therapy ; Rats, Sprague-Dawley ; Rats ; Depression/psychology* ; Humans ; Reactive Oxygen Species/metabolism* ; Disease Models, Animal ; Acupuncture Points

OBJECTIVE: To investigate the clinical features, distribution of pathogenic bacteria, and drug resistance of bloodstream infection in children with acute leukemia. METHODS: Clinical data of 93 blood culture-positive children with acute leukemia from January 2015 to December 2019 in Department of Pediatrics, The Second Hospital of Anhui Medical University were analyzed retrospectively. RESULTS: In these 93 cases, 78 cases were in the period of neutrophil deficiency. There were 54 Gram-negative bacteria (G^-) (58.1%) found through blood culture, and the top 4 strains were Escherichia coli (15.1%), Klebsiella pneumoniae (13.9%), Pseudomonas aeruginosa (6.5%), and Enterobacter cloacae (6.5%). There were 39 Gram-positive bacteria (G⁺) (41.9%) detected, and the top 4 strains were Staphylococcus epidermidis (10.8%), Streptococcus pneumoniae (6.5%), Staphylococcus hemolyticus (5.4%), and Staphylococcus human (5.4%). Among 74 strains of pathogenic bacteria from acute lymphoblastic leukemia (ALL) children, there were 29 strains of G⁺ bacteria (39.2%) and 45 strains of G^- bacteria (60.8%). While in 19 strains from acute myeloblastic leukemia (AML) patients, G^- bacteria accounted for 47.4% and G⁺ bacteria accounted for 52.6%. In 15 ALL children without neutropenia, G⁺ bacteria made up the majority of the strains (66.7%). In the 93 strains of pathogenic bacteria, 13 (13.9%) strains were multidrug-resistant. Among them, extended-spectrum β-lactamases accounted for 42.9%, carbapenemase-resistant enzyme Klebsiella pneumoniae 15.4%, and carbapenemase-resistant enzyme Enterobacter cloacae strains 33.3%, which were detected from G^- bacteria. While, 13.3% of methicillin-resistant coagulase-negative Staphylococci accounted for 13.3% detected from G⁺ bacteria, but linezolid, vancomycin, teicoplanin Staphylococcus and Enterococcus resistant were not found. The average procalcitonin (PCT) value of G^- bacteria infection was (11.02±20.282) ng/ml, while in G⁺ infection it was (1.81±4.911) ng/ml, the difference was statistically significant (P<0.05). The mean value of C-reactive protein (CRP) in G^- infection was (76.33±69.946) mg/L, and that in G⁺ infection was (38.34±57.951) mg/L. The prognosis of active treatment was good, and only one case died of septic shock complicated with disseminated intravascular coagulation (DIC) and gastrointestinal bleeding caused by carbapenemase-resistant enzyme enterobacteriaceae. CONCLUSION G^- is the major bacteria in acute leukemia children with bloodstream infection, but the distribution of ALL and AML strains is different. G^- bacteria dominates in ALL, while G⁺ bacteria and G^- bacteria are equally distributed in AML. Non-agranulocytosis accompanied by bloodstream infections is dominant by G⁺ bacteria. The mean value of PCT and CRP are significantly higher in G^- bacteria infection than in G⁺ bacteria.
Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Bacteria ; Child ; Drug Resistance, Bacterial ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Microbial Sensitivity Tests ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Procalcitonin ; Retrospective Studies ; Sepsis/drug therapy*

Ferroptosis is a novel cell death mode proposed in recent years, which is characterized by intracellular iron-dependent lipid peroxidation. Its mechanisms include lipid peroxidation, iron accumulation and the imbalance of antioxidant system. The crosstalk between ferroptosis and asthma is gradually deepening. Elucidating the specific mechanism of ferroptosis in regulating asthma is helpful to broaden the understanding of the pathology of asthma. This paper expounds the role of ferroptosis in airway epithelial cells in the occurrence and development of asthma from three perspectives: lipid peroxidation, iron accumulation and the imbalance of antioxidant system, hoping to find new targets and strategies for asthma treatment.

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Hand, foot and mouth disease (HFMD) is an acute infectious disease induced by enterovirus. More than 30 pathogenic viruses for hand, foot and mouth disease have been discovered, of which enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the most common. Enterovirus 71 (EV-A71) is also the main cause of severe hand, foot and mouth disease. In recent years, it has been discovered that Coxsackievirus A6 (CV-A6) infection has broken out in many regions of the world, and the pathogenicity rate is increasing, which indicatesthat it may rise to become a new major pathogenic agent of hand, foot and mouth disease. Hand, foot and mouth disease has become a global public health problem. Therefore, research on the pathogenic mechanism of multiple enteroviruses that induce hand, foot and mouth disease and analysis of its epidemiology will become the top priority of prevention, control and treatment of the disease.

Objective:To confirm the protective effect of Xiangsha Yuyang decoction on acetic acid-induced gastric ulcer model rats and explore its mechanism， so as to provide experimental basis for clinical drug use. Method:The 60 SPF Wistar rats were randomly divided into 6 groups： group， model group， high， middle and low dose groups of Xiangsha Yuyang decoction and omeprazole control group. The rat model of gastric ulcer was induced by acetic acid. The rats in the high， middle and low dose groups of Xiangsha Yuyang decoction were intragastrically administered at the dose of 28，14，7 g·kg^-1， and with omeprazole at the dose of 4.17 g·kg^-1in normal saline， respectively. The rats in the blank group and model group were intragastrically infused with the same volume of normal saline once a day. After 14 days of continuous treatment， the rats were killed， the blood was collected， the area and inhibition rate of gastric ulcer were measured and calculated， the histopathological sections of gastric mucosa were made and the state of gastric mucosal injury was observed， and the changes of gastric mucosal repair factor， gastric tissue related protein， oxidative stress factor and inflammatory factor in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Detected the expression of p62 Kelch-like epichlorohydrin-related protein 1 （Keap1）， nuclear transcription factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） signal pathway-related proteins in gastric mucosa by Western blot. Result:Compared with control group， the gastric mucosa of the model group showed obvious pathological changes and a large number of leukocytes infiltrated. In model group， the ulcer area was significantly increased（P<0.01）， the contents of mucin mucoprotein 5AC （MUC5AC）， epidermal growth factor （EGF）， superoxide dismutase （SOD） and increased prostaglandin E₂ （PGE₂） were significantly decreased（P<0.01）， the gastrin （GAS）， 8-hydroxydeoxyguanosine （8-OHdG）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2） were significantly increased. The expression of HO-1 and Nrf2 protein decreased significantly（P<0.01）， the content of Keap1 increased significantly （P<0.05）， and the expression of p62 protein decreased. Compared with model group， the hierarchical structure of cells in Xiangsha Yuyang decoction high dose group and omeprazole group were clearer and regular， middle and low dose groups could also repair gastric mucosa to a certain extent. The high and middle dose groups of Xiangsha Yuyang decoction could significantly reduce the gastric ulcer area of acetic acid-induced gastric ulcer rat model （P<0.01） and increase the ulcer inhibition rate. It can effectively promote the expression of MUC5AC and EGF in gastric mucosa， decrease the level of GAS（P<0.05，P<0.01）， decrease the level of 8-OHdG and MDA， increase the activity of SOD（P<0.01）， decrease the expression level of TNF-α and COX-2， increase the content of PGE₂， and significantly increase the amount of Nrf2 and HO-1 protein in gastric mucosa（P<0.01）. The high dose group of Xiangsha Yuyang decoction could decrease the protein expression of Keap1（P<0.05） and increase the expression of p62 protein. Conclusion:Xiangsha Yuyang decoction is effective in the treatment of acetic acid-induced gastric ulcer model rats， which can effectively reduce the ulcer area， increase the ulcer inhibition rate and protect the ulcer tissue. Its mechanism may be related to activating p62/Keap1/Nrf2 signal pathway and regulating the expression of related genes so as to improve inflammatory response and regulate oxidative stress response.

Immunotherapy has dramatically altered the treatment of non-small cell lung cancer. Currently, the emergence of combination strategies in immunotherapy has brightened the prospects of improved clinical outcomes and manageable safety profiles in the first/second-line settings. However, sub-optimal response rates are still observed in several clinical trials. Hence, alternative combination models and candidate selection strategies need to be explored. Herein, we have critically reviewed and commented on the published data from several clinical trials, including combined immunotherapy and chemotherapy, anti-angiogenic agents, epidermal growth factor receptor/anaplastic lymphoma kinase tyrosine kinase inhibitors, radiotherapy, and other immune checkpoint inhibitors.
Angiogenesis Inhibitors/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immunotherapy ; Lung Neoplasms/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Computed Tomography Angiography ; Coronary Angiography ; Coronary Artery Disease/diagnosis* ; Coronary Vessels ; Humans ; Machine Learning ; Predictive Value of Tests

OBJECTIVE: To study the risk factors and infection characteristics of nosocomial infection in children with acute lymphoblastic leukemia (ALL) and analyze the relationship between different nutritional status and nosocomial infection, early treatment response. METHOD: The clinical data of 133 children with ALL treated with CCCG-ALL-2015 from June 2016 to June 2019 (chemotherapy stage, risk level, MRD), infection during hospitalization (course of infection, laboratory indicators, sites of infection, outcome) and nutritional status (sex, age, height/ length, weight) were enrolled. The Chi 2 test and Logistic regression analysis were used for statistical analysis. RESULTS: The rate of nosocomial infection was 19.9% in 133 children with ALL, in which 3 were infection-related death. Sex, immunophenotype and risk showed no significantly affect on the occurrence of nosocomial infection (P＞0.05), but neutrophil count, hemoglobin level, platelet count, chemotherapy stage, length of stay in hospital and nutritional status showed affect on the occurrence of nosocomial infection (P＜0.05). Logistic multivariate regression analysis showed that chemotherapy stage, length of hospital stay, neutrophils and nutritional status were the independent risk factors, in which the respiratory tract infection was the most common. Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 44.1%, 52.9% and 2.9% respectively. The negative rate of MRD in day 19 and day 46 between different nutritional status groups showed statistically significant (P＜0.05). CONCLUSION Neutrophil count, chemotherapy stage, length of stay in hospital and nutritional status are independent risk factors for nosocomial infection. Among of them, nutritional status negatively correlated with nosocomial infection, and the poorer nutritional status, the higher risk of nosocomial infection. Malnutrition, overweight and obesity can affect the early treatment response of ALL children. The level of nutrition at first diagnosis can be used as a bad factor to evaluate the early treatment response of ALL children.
Child ; Cross Infection ; Gram-Negative Bacteria ; Humans ; Nutritional Status ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies

OBJECTIVE: To detect and analyze the mutation status of FANCJ gene in adult AML patients, so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese. METHODS: The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients. The primers were designed for FANCJ gene coding region, the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing; the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software. RESULTS: The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region, which were as followed: exon5:c.G430A:p.A144T, exon6:c.A587G:pN196S, exon9:c.C1255T:p.R419W, exon10:c.G1442A:p.G481D, exon11:c.C1609G:p.L537V, exon16:c.C2360T:p.P787L, exon17:c.C2440T:p.R814C, exon19:c.C2608T:pH870Y, exon19:c.A2686G:p.I896V, exon19:c.C2830G:p.Q944E, exon20:c.G3412A:p.D1138N. Among them, the repeatability existed in mutations of A144T, N196S, R814C, I896V and Q944E. Beside, the mutation sites of A144, R419, G381, L537, P787, H870, Q944 and D1138 were highly conserved in different organisms. CONCLUSION Among 222 adult AML patients, the mutations of FANCJ gene have been found in 26 patients, moreover, the mutation sites are relatively conserved in different organisms, and possess important fanction. The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.
Adult ; DNA Primers ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Polymerase Chain Reaction ; Prognosis