Objective To use network pharmacology to mine and predict the targets and related signaling pathways of Miaoyao Yiai Tang(Miao-Yi-Ai-Tang,MYAT)in the treatment of small cell lung cancer(SCLC).And animal experiments to verify its mechanism of action,to provide a theoretical basis for basic experiments and clinical applications.Methods The active ingredients of MYAT were obtained from the TCMSP database,combined with PubMed data,Swiss Target Prediction database and Uniprot database to obtain potential targets;SCLC-related genes were collected through the DrugBank database,Genecards database,OMIM database and TTD database,and the Venny 2.1 platform After obtaining the intersection genes of MYAT and SCLC,import them into the STRING database,construct a protein-protein interaction(PPI)network,use Cytoscape 3.9.1 software for visual analysis,and use Metascape database for GO enrichment analysis and KEGG pathway analysis,to predict the direct action target and signaling pathway of MYAT in the treatment of SCLC.Using AutoDock Tools 1.5.7 software for molecular docking to verify the close relationship between the two.For cytological experiment verification,the cultured cells were treated with MYAT and the expression of β-catenin,AXIN,c-myc was detected by qPCR,and the expression of β-catenin in the cells was detected by Western blot;animal experiments were established to establish a subcutaneous xenograft tumor model of lung cancer NCI-H446,to observe the effect of MYAT on tumor growth.Results A total of 65 effective components of MYAT,1368 SCLC genes,and 260 MYAT-SCLC intersection genes were obtained.Enrichment analysis showed that they were related to cancer pathways,PD-L1/PD-1 pathways,NF-κB pathways,Wnt and other signaling pathways.The results of molecular docking validation showed that the binding energies of active components and core target proteins were all<0 kJ·mol-1,which indicated that the protein could spontaneously bind to active components and be stable.Cell experiments showed that the expression levels of β-catenin,c-myc and AXIN mRNA were significantly down-regulated in the MYAT group(P<0.05).Animal experiments show that:MYAT can significantly inhibit the growth of tumors in vivo.Conclusion Miao-Yi-Ai-Tang can inhibit the proliferation of small cell lung cancer through Wnt/β-catenin signaling pathway.

Aim To investigate the regulatory and an-ti-tumour effects of baicalein on mouse hepatocellular carcinoma cells and mouse macrophage co-cultures.Methods In vitro experiments,mouse hepatocellular carcinoma cell H22 and mouse macrophage RAW264.7 were randomly divided into a blank group and different concentrations of gradient administration group(5,10,20,40,80 mg·L-1),and the cell activity was detec-ted by CCK-8 assay;the two kinds of cells were co-cultured in Transwell chambers of 6-well plates for 48 h,and were randomly divided into the blank,model,and low,medium,and high baicalin groups(10,20,40 mg·L-1).Cell scratch and invasion assays,ELISA kits were used to detect TNF-α and IL-10 factor levels,and Western blot was used to determine the lev-els of CCNA2 and related proteins.The levels of TNF-α and IL-10 were detected by ELISA kits,and the ex-pression levels of CCNA2 and related proteins were de-tected by Western blot.In vivo experiments,H22 sub-cutaneous tumour model was established and randomly divided into the blank,positive,model and drug-ad-ministered groups.Mouse spleen,thymus and tumour indices were counted,and immunohistochemistry and Western blot were employed to detect the expression levels of CCNA2 and macrophage-related indexes in tumour tissues.Results Different doses of baicalein had a significant inhibitory effect on H22 and no signif-icant cytotoxicity on M0-type RAW264.7;the mor-phology of M0-type RAW264.7 cells was changed after co-culture,TNF-α was elevated and IL-10 was re-duced in the baicalein group;the results of the cell scratch assay and invasion assay found that baicalein inhibited M2-type macrophage invasion and metastasis;Arg1,p-p38/p38,p-stat3/stat3,N-cadherin,CCNA2 decreased significantly and Inos and E-cadherin in-creased significantly in the baicalein group;CCNA2,CD206 expression decreased significantly and CD86 expression increased significantly in the administered group.Conclusions Baicalein reverses M2-type mac-rophage polarisation and pro-carcinogenic functions and inhibits M2-type macrophage migration and invasion by modulating M2-type macrophage-related signalling pathways.

OBJECTIVE: To explore the clinical effect of Kirschner wire intramedullary fixation in the treatment of both-bone forearm fractures in children of high altitude area. METHODS: From August 2020 to December 2021, 19 children were treated with Kirschner wire intramedullary fixation including 11 males and 8 females, aged from 4 to 13 years old with an average of (8.16±2.71) years old. The course of disease was 1 to 10 days, with a mean of (4.11±2.51) d. First, close reduction was performed. If the reduction was unsuccessful, limited open reduction was performed, followed by Kirschner wire intramedullary fixation of the radius and ulna. The fracture healing was evaluated by X-ray after operation, and the curative effect was evaluated by Anderson forearm function score standard. RESULTS: The wound healed well after operation, 2 cases had clinical manifestations of needle tail irritation after operation, and the symptoms disappeared after removing the internal fixation. The average follow-up time was(7.68±3.50) months (3 to 14 months). X-ray showed that all fracture healing in follow-up, Anderson forearm function score showed excellent in 16 cases, good in 2 cases and fair in 1 case at the final follow-up. CONCLUSION Children with fractures in plateau areas often have delayed medical treatment, lack of medical conditions and insufficient compliance. Based on these characteristics, Kirschner wire intramedullary fixation for the treatment of children's double forearm fractures has the advantages of small injury and rapid recovery. It is a kind of operation method that can be popularized.
Male ; Female ; Humans ; Child ; Child, Preschool ; Adolescent ; Bone Wires ; Forearm ; Altitude ; Treatment Outcome ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods* ; Radius Fractures/surgery* ; Fracture Fixation, Intramedullary/methods*

Child ; Humans ; Chromosomes, Human, Pair 16 ; Leukemia, Myeloid, Acute ; Neoplasms, Multiple Primary/genetics* ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein FUS/genetics* ; Sarcoma, Myeloid/genetics* ; Transcriptional Regulator ERG/genetics* ; Translocation, Genetic

This study was aimed to understand the current status of the antimicrobial resistance and molecular distribution of Campylobacter in various poultry in Jiaodong area,to provide a basis for effective prevention and control of the Campy-lobacter risk to poultry products and human health.Campylobacter was isolated and identified from 565 cloacal samples collect-ed in the Jiaodong area from August to October 2021 through conventional bacterial isolation and culture,mass spectrometry,microbroth dilution and multilocus sequence typing(MLST).The drug resistance and molecular typing of 131 representative strains(67 Campylobacter jejuni and 64 Campylobacter coli)were studied separately.Antimicrobial resistance analysis indica-ted that 131 isolates were highly resistant to ciprofloxacin,nalixic acid and tetracycline,with resistance rates of 96.21％,96.21％and 95.45％,respectively.Except for 2 strains,62 strains of C.coli were completely resistant to these three drugs(100％).A total of 65 strains of 131 strains were multidrug re-sistant,and the overall multidrug resistance rate was 49.62％,among which 11 strains(16.42％)of C.jejuni were resistance to 3-5 antibiotics,and 54 strains(84.38％)of C.coli were re-sistance to 3-6 antibiotics.Among the isolates from different poultry sources,waterfowl isolates were the most resistant,fol-lowed by broiler isolates.The MLST typing results revealed 72 alleles and 35 sequence types obtained from 67 strains of C.je-juni,and the distribution was relatively dispersed,without a dominant ST type and homologous complex.A total of 27 alleles and 19 sequence types were obtained from 64 strains of C.coli.Moreover,59.38％(38/64)strains were homologous complex CC-828,in which the ST-1586 sequence type was most frequent,followed by ST-825.ST-1586,ST-9944 and ST-3735 were the main sources of C.coli in broilers,and ST-825 and ST-1586 were the main sources of C.coli in waterfowl.Differences in C.jejuni and C.coli carriage were observed among poultry in the Jiaodong area.Carriage of the two bacteria was more common in laying hens than in broilers and waterfowl.C.jejuni from poultry in the Jiaodong area was highly resistant to ciprofloxacin,nalixic acid and tetracycline,but had good sensitivity to other drugs.C.coli was highly resistant to a variety of antibiotics,and multiple drug resistance was common.St-type dispersal of C.jejuni showed high genetic diversity.C.coli was cloned and transmitted mainly by ST-1586 in broiler chickens and waterfowl.Poultry carry C.jejuni,which can cause serious diseases in humans.Therefore,dynamic monitoring of Campylobacter from poultry should be strengthened.

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.
Humans ; Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Abelmoschus ; Flavones/pharmacology* ; Podocytes ; Tumor Necrosis Factor-alpha/metabolism* ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Fibrosis ; Threonine/pharmacology* ; Collagen/metabolism* ; Serine/pharmacology* ; Diabetes Mellitus/drug therapy*

Objective: To understand the risk factors and antibiotics-resistant patterns of invasive Acinetobacter baumannii infection in Children. Methods: This retrospective study was conducted in 6 tertiary hospitals from January 2016 to December 2018. The basic information, clinical data and the results of antimicrobial susceptibility testing were collected from the 98 pediatric inpatients with Acinetobacter baumannii isolated from blood or cerebrospinal fluid and analyzed. According to the susceptibility of the infected strains to carbapenems, they were divided into carbapenem-sensitive Acinetobacter baumannii (CSAB) group and carbapenem-resistant Acinetobacter baumannii (CRAB) group. According to the possible sources of infection, they were divided into nosocomial infection group and community infection group. Chi-square test or Fisher exact test were used to analyze categorical variables and rank sum test were used to analyze continuous variables. The risk factors of invasive CRAB infection in children were analyzed by Logistic regression. Result: There were 56 males and 42 females in 98 cases. The onset age of patients was 8 (2, 24) months. There were 62 cases (63%) from rural area. A total of 87 cases (89%) were confirmed with bloodstream infection, and 12 cases (12%) confirmed with meningitis (1 case was accompanied with bloodstream infection). In these patients, 66 cases (67%) received invasive medical procedures or surgery, 54 cases (55%) received carbapenems-containing therapy. Twenty-four cases were infected with CRAB, and 74 cases with CSAB. The onset age of cases in CRAB group was lower than that in CSAB group (4 (1, 9) vs. 10 (4, 24) months, Z=-2.16, P=0.031). The proportions of hospitalization in intensive care unit, carbapenem antibiotics using, pneumonia and adverse prognosis in CRAB group were higher than those in CSAB group (6 cases (25%) vs. 4 cases (5%), 18 cases (75%) vs. 36 cases (49%), 17 cases (71%) vs. 17 cases (23%), 6 cases (25%) vs. 4 cases (5%), χ²=5.61, 5.09, 18.32, 5.61, all P<0.05). Seventy-seven cases were nosocomial infection and 21 cases were hospital-acquired infection. The proportion of children hospitalized in high-risk wards for nosocomial infections, length of hospitalization, number of antimicrobial therapy received and duration of antimicrobial therapy were higher in the hospital associated infection group than those in the community acquired infection group (all P<0.05). Logistic regression analysis showed that children from rural area (OR=8.42, 95%CI 1.45-48.88), prior mechanical ventilation (OR=12.62, 95%CI 1.31-121.76), and prior antibiotic therapy (OR=4.90, 95%CI 1.35-17.72) were independent risk factors for CRAB infection. The resistance percentage of CSAB isolates to many classes of antibiotics was <6% except to gentamicin, which was as high as 20% (13/65). All CRAB isolates of resistant to ampicillin-sulbactam (20/20), cefepime (23/23), piperacillin (17/17), meropenem (23/23) and imipenem (24/24) were 100%. The resistance percentage to other antibiotics were up to 42%-96%. Conclusions: Most of invasive Acinetobacter baumannii infection in children in China are hospital-acquired. The outcome of invasive CRAB infection was poorer than that of CSAB infection. The drug resistance rate of CRAB strains isolated is high. Living in rural area, prior invasive mechanical ventilation and prior antibiotic therapy were independent risk factors for invasive CRAB infection. The prevention and control of nosocomial infection and appropriate use of antibiotics to reduce Acinetobacter baumannii infection.
Acinetobacter Infections/epidemiology* ; Acinetobacter baumannii ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/therapeutic use* ; Child ; Cross Infection/epidemiology* ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Retrospective Studies ; Risk Factors ; Sepsis

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Ischemic stroke is one of the main causes of death and long-term disability worldwide, which seriously affects the quality of life of patients and brings a heavy economic burden to families and society. Epidemiological studies have shown that stroke has become the second leading cause of death and major disabling disease in the world, with the characteristics of high morbidity, high recurrence, and high mortality. Epigenetic mechanism is the molecular process where gene expression and function in each cell are dynamically regulated and interconnected and a biological mechanism that changes genetic performance without changing the DNA sequence, including DNA methylation, histone modifications, and non-coding RNA. However, the research on epigenetics is currently focused on other diseases such as tumors. Recent studies have found that epigenetics has received extensive attention in the past few decades as a key factor involved in the pathophysiological process of ischemic stroke. The present study introduced the mediation of epigenetics in the induction of stroke, summarized the potential drug targets for these mechanisms in the treatment of stroke, and further explored the significance of traditional Chinese medicine(TCM) against cerebral ischemia injury based on TCM classification of stroke.
DNA Methylation ; Epigenesis, Genetic ; Humans ; Ischemic Stroke/genetics* ; Quality of Life ; RNA, Untranslated/metabolism* ; Stroke/genetics*

ObjectiveTo investigate the analgesic effect and its mechanism of （-）-gallocatechin gallate （EGCG） on high-frequency stimulation （HFS）-induced chronic primary pain in female mice. MethodsThe model of chronic primary pain in female mice were established by HFS of sciatic nerve in left hind limb at 10 V （100 Hz， 0.5 ms， 4 trains of 1-s duration at 10-s intervals）. The mice were randomly divided into sham operation group， vehicle （saline） + HFS group， different concentrations of EGCG + HFS groups （4~5 mice in each group）. 10 μL EGCG （10， 20， 50， 200 μmol/L） or vehicle was injected intrathecally 1 h before surgery. The therapeutic effect of EGCG was evaluated by paw withdrawal threshold （PWT） and analgesic efficiency. Immunofluorescence of lumbar spinal cord was used to evaluate the possible mechanisms. ResultsCompared with vehicle HFS group， intrathecal administration of EGCG alleviated HFS-induced mechanical allodynia in a dose-dependent manner， and the maximum analgesic efficiency was 84.95%. EGCG also blocked the increases in c-Fos （a marker for neuronal excitability） positive neurons and the expressions of calcitonin gene-related peptide （CGRP⁺） terminals， Iba1 （a marker for microglia） and GFAP （a marker for astrocytes） in the ipsilateral spinal dorsal horn. ConclusionIntrathecal injection of EGCG exerts an analgesic effect against HFS-induced chronic primary pain， mediated by inhibiting the increases in presynaptic CGRP⁺ terminals， postsynaptic neuronal excitability and glial activation in the spinal dorsal horn.