OBJECTIVE To study the effects of Wubao capsule on airway inflammation in asthmatic model mice by regulating upstream and downstream cytokines of type Ⅱ innate lymphoid cells （ILC2s）. METHODS Totally 40 female BABL/c mice were randomly divided into normal group， model group， positive control group （dexamethasone 1 mg/kg）， Wubao capsule low-dose and high-dose groups （0.5， 1 g/kg）， with 8 mice in each group. Asthma models were induced by ovalbumin （OVA） sensitization and nebulization. Each group was given normal saline or drug intragastrically for 7 consecutive days. The contents of IgE and OVA-IgE in serum， the contents of interleukin 5 （IL-5）， IL-9， IL-13， IL-25， IL-33， thymic stromal lymphopoietin （TSLP） and mucin 5AC （MUC5AC） in bronchoalveolar lavage fluid （BALF） were determined by ELISA. HE staining was used to observe the pathological changes of lung tissues in mice. PAS staining was used to observe the changes of goblet cell proliferation in each group. The number of ILC2s in lung tissue was determined by flow cytometry （except for Wubao capsule low-dose group）. RESULTS Compared with model group， the contents of IgE and OVA-IgE in serum and the contents of IL-5， IL-9， IL-13， IL-25， IL-33， TSLP and MUC5AC in BALF were significantly reduced in Wubao capsule high-dose and low-dose groups （P＜0.01）. The infiltration of inflammatory cells and the thickening of basement membrane in lung tissue was alleviated to varying degrees， and the proliferation of goblet cells was inhibited； the number of ILC2s in lung tissues of mice in Wubao capsule high-dose group was significantly reduced （P＜0.01）. CONCLUSIONS Wubao capsule could effectively reduce the number of ILC2s in lung tissue， the contents of upstream and downstream cytokines of ILC2s in BALF of asthmatic model mice， so as to inhibit the airway inflammation and improve asthma.

Resveratrol (RES), a natural polyphenolic phytochemical, has been suggested as a putative anti-aging molecule for the prevention and treatment of Alzheimer's disease (AD) by the activation of sirtuin 1 (Sirt1/Sir2). In this study, we tested the effects of RES and Sirt1/Sir2 on sleep and courtship memory in a Drosophila model by overexpression of amyloid precursor protein (APP), whose duplications and mutations cause familial AD. We found a mild but significant transcriptional increase of Drosophila Sir2 (dSir2) by RES supplementation for up to 17 days in APP flies, but not for 7 days. RES and dSir2 almost completely reversed the sleep and memory deficits in APP flies. We further demonstrated that dSir2 acts as a sleep promotor in Drosophila neurons. Interestingly, RES increased sleep in the absence of dSir2 in dSir2-null mutants, and RES further enhanced sleep when dSir2 was either overexpressed or knocked down in APP flies. Finally, we showed that Aβ aggregates in APP flies were reduced by RES and dSir2, probably via inhibiting Drosophila β-secretase (dBACE). Our data suggest that RES rescues the APP-induced behavioral deficits and Aβ burden largely, but not exclusively, via dSir2.
Animals ; Alzheimer Disease/metabolism* ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/metabolism* ; Drosophila/physiology* ; Drosophila Proteins/metabolism* ; Resveratrol/pharmacology* ; Sirtuin 1 ; Sleep

Objective To investigate the protective effect and molecular mechanism of bloodletting acupuncture at Jing-well points on acute high-altitude hypoxia brain injury through regulating PI3K/AKT/mTOR signaling pathway-mediated mitochondrial autophagy,and to provide an effective target and theoretical basis for the clinical use of bloodletting acupuncture at Jing-well points to prevent and treat acute high-altitude hypoxia brain injury.Methods Male SD rats were randomly divided into Control group(n=15)and experimental group,and the experimental group was divided into Model group(n=15),Bloodletting Acupuncture at Jing-well Points of hand group(BAJP group,n=15),Bloodletting Acupuncture at Non-Acupoint group(BANA group,n=15).The low pressure oxygen chamber was depressurized to 6000 m altitude,and the rats in each experimental group were treated with low-pressure hypoxia for 72 h to replicate the acute high-altitude hypoxia brain injury rat model.The rats in the BAJP group were bled according to the order of"Shaoshang"(LU11),"Shangyang"(LI1),"Zhongchong"(PC9),"Guanchong"(SJ1),"Shaochong"(HT9),"Shaoze"(SI1),once a day for 7 days.The rats in the BANA group were bled by cutting the tail tip daily,and the amount of blood bled was 15-20 μL in both groups.The expression levels of PI3K,AKT and mTOR in hippocampal tissues of rats were detected by Western blot;AKT and mTOR mRNA expression levels in hippocampal tissues of rats were detected by PCR.Results Compared with the Control group,the number of degenerative necrotic vertebral cells in CA1 area of hippocampal tissue,swelling of mitochondria,appearance of autophagosomes,and increase of apoptosis in hippocampal tissue of Acute High-altitude Hypoxia(AHH)rats were significantly increased;After bloodletting acupuncture at Jing-well points of hand treatment,various brain injury manifestations in AHH rats were alleviated;Bloodletting acupuncture at non-acupoint had no significant ameliorating effect on AHH rats′ brain injury.Western blot detected a significant decrease in the phosphorylation levels of PI3K,AKT,and mTOR in the hippocampal tissues of AHH rats compared to Control group rats(P<0.01),and the phosphorylation levels of the three molecules were further decreased after bloodletting acupuncture at Jing-well points of hand treatment(P<0.01),and bloodletting acupuncture at non-acupoint treatment did not have significantly affect on the phosphorylation levels of these molecules(P>0.05),and AKT,mTOR mRNA expression levels further demonstrated the above trend.Conclusion Bloodletting acupuncture at Jing-well points of hand can play a protective role against acute high-altitude hypoxia brain injury with points specificity,and the mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway to promote the elevated level of mitochondrial autophagy,improve mitochondrial physiology,and enhance the body′s ability to resist apoptosis and hypoxia.

ObjectiveTo investigate the effects of aerobic exercise on sleep-deprived rats positioning cruise and space exploration activities, synaptic mechanism, involving hippocampal neuron morphology, dendritic spine density, synaptic related proteins and cyclic adenosine phosphate reactive element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway. MethodsA total of 48 Sprague-Dawley rats were randomly divided into control group (n = 12), model group (n = 12), model-exercise group (n = 12) and exercise group (n = 12). The model-exercise group and the exercise group accepted aerobic exercise with treadmill for four weeks. After exercise intervention, the model group and the model-exercise group were continuously deprived sleep for 72 hours with a multi-platform water environment. They were assessed with Morris Water Maze of positioning cruise and space exploration. The morphology and density of dendritic spines in hippocampal neurons were observed with HE staining and Golgi staining. The expression of hippocampal proteins of postsynaptic density protein 95 (PSD95), synapsin (SYN), growth-associated protein 43 (GAP43), Rac1, BDNF, p-CREB and CREB were measured with Western blotting. ResultsCompared with the control group, the latency and the total swimming distance increased in the model group (P < 0.05); the number of crossing the platform, the target quadrant residence time and distance decreased (P < 0.05); the neurons in the hippocampal CA1 region were disordered, the total density of dendritic spines per unit length and the density of mature, immature and filamentous pseudopodia dendritic spines decreased (P < 0.05); and the expression of PSD95, SYN, GAP43, Rac1, BDNF, p-CREB and CREB decreased (P < 0.05). Compared with the model group, the latency and total swimming distance of the model-exercise group decreased (P < 0.05); the target quadrant residence time and distance increased (P < 0.05); the number of neurons in the hippocampal CA1 region increased and arranged neatly; the total density of dendritic spines per unit length and the density of mature, immature and filamentous pseudopod dendritic spines increased (P < 0.05); and the expression of PSD95, SYN, GAP43, Rac1, BDNF, p-CREB and CREB increased (P < 0.05). ConclusionAerobic exercise can alleviate the learning and memory impairment of sleep-deprived rats, which may relate to the regulation of CREB/BDNF signaling pathway in hippocampus for improvement of synaptic plasticity.

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China ; Dwarfism/genetics* ; Humans ; Intellectual Disability ; Osteochondrodysplasias/genetics* ; Pedigree

Objective:To explore the value of Caprini risk assessment scale and serum D-dimer in early prediction of postoperative lower extremities deep vein thrombosis (DVT) in patients with gastrointestinal malignant tumor.Methods:A total of 240 patients with gastrointestinal malignant tumors treated in Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from Jan to Oct 2020 were analyzed retrospectively.Results:Caprini score was 4 in 8 cases, 5-7 in 217 cases, and 8 in 15 cases. Sixty-seven patients developed lower extremity DVT after operation. No patients with Caprini score of 4 had DVT, 57 cases (26.3%) with a score of 5-7 had DVT; 10 cases whose score were ≥8 points (66.7%) developed DVT. There was a higher incidence of lower extremity DVT in patients ≥8 points than those of 5-7 points after surgery ( P<0.01). The postoperative Caprini score of the DVT group was higher than that of the non-DVT group (6.37±1.01 vs. 5.80±0.94, t=4.108, P<0.001). D-dimer on the first day after operation in DVT group (4.08±2.27 vs. 2.01±1.04, t=7.715, P<0.001) and the level of serum D-dimer (2.93±1.81 vs. 2.30±1.21, t=2.631, P<0.001) on day 3 was higher than that in the non-DVT group. According to the ROC curve, the best cut-off value for serum D-dimer to predict lower extremity DVT on the first postoperative day was 2.84 mg/L, the sensitivity was 70.1%, the specificity was 87.3%, and the area under the curve (AUC) was 0.815. The best cut-off value of D-dimer for predicting lower limb DVT on day 3 after surgery was 1.67 mg/L, sensitivity was 85.1%, specificity was 34.7%, and AUC was 0.611. Conclusions:Patients with gastrointestinal malignant tumors have a high incidence of postoperative lower extremity DVT. When the serum D-dimer exceeds 2.84 mg/L on the first postoperative day, the likelihood of postoperative lower extremity DVT is higher.

Objective? To explore the application of active pain assessment in pain management of enhanced recovery after surgery. Methods? From April 2017 to November 2017, we selected 120 patients with abdominal operation of enhanced recovery after surgery (ERAS) ward in hepatobiliary surgery at the Affiliated Hospital of Xuzhou Medical University by convenient and purposive sampling. All of the patients were divided into control group (n=60) and observation group (n=60) with the method of random number table. Control group carried out routine pain nursing of ERAS. On the basis of that in control group, observation group implemented postoperative pain management with the active pain assessment scale. We compared the times of effective cough and turning over in bed within 24 hours after surgery, pain score of function activity for the first time, time of out-of-bed activity and passage of gas by anus for the first time. Results? Between control group and observation group, the times of effective cough were (3.867±1.454) and (6.483±2.313) respectively with a statistical difference (P＜0.01); the times of turning over in bed were (4.450±1.596) and (6.133±1.874) respectively with a statistical difference (P＜0.01); the pain scores of function activity for the first time were (5.864±1.524) and (3.725±1.572) respectively with a statistical difference (P＜0.01); the time of out-of-bed activity for the first time was (12.483±5.147) hours and (8.800±3.564) hours respectively with a statistical difference (P＜0.01);the time of passage of gas by anus for the first time was (13.264±3.514) hours and (8.345±1.725) hours respectively with a statistical difference (P＜0.01). Conclusions? ERAS combined with active pain assessment is practical. Active pain assessment could effectively evaluate the postoperative painless management,ensure that the postoperative functional exercise is carried out and promote patient rehabilitation.

Seizures during sleep increase the probability of complication and sudden death. Effective prediction of seizures in sleep allows doctors and patients to take timely treatments to reduce the aforementioned probability. Most of the existing methods make use of electroencephalogram (EEG) to predict seizures, which are not specific developed for the sleep. However, EEG during sleep has its characteristics compared with EEG during other states. Therefore, in order to improve the sensitivity and reduce the false alarm rate, this paper utilized the characteristics of EEG to predict seizures during sleep. We firstly constructed the feature vector including the absolute power spectrum, the relative power spectrum and the power spectrum ratio in different frequencies. Secondly, the separation criterion and branch-and-bound method were applied to select features. Finally, support vector machine classifier were trained, which is then employed for online prediction. Compared with the existing method that do not consider the characteristics of sleeping EEG (sensitivity 91.67%, false alarm rate 9.19%), the proposed method was superior in terms of sensitivity (100%) and false alarm rate (2.11%). This method can improve the existing epilepsy prediction methods and has important clinical value.

Objective To explore the clinical efficacy and outcomes of thrombus aspiration in ST-elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PPCI). Methods A total of 664 cases of STEMI patients undergoing PPCI from Tianjin Chest Hospital from January 2013 to March 2015 were retrospectively analyzed. Patients were divided into two groups:primary PCI after thrombus aspiration group and conventional primary PCI without thromobus aspiration group. The base-line clinical characteristics, and the procedure of percutaneous coronary intervention were similar between two groups. The TIMI flow, LVEF, one-month outcomes and 12-month outcomes were compared between two groups. Results There were significant higher TIMI flow, LVEF in primary PCI after thrombus aspiration group than those of conventional primary PCI without thromobus aspiration group (P<0.05). At one-month follow-up, there were no significant differences in major adverse cardiac events (MACE) between the two groups. At 12-month follow- up, there were no significant differences in cardiovascular death, recurrent myocardial infarction and new hospitalization between two groups. The incidence of recurrent angina was significantly higher in non-aspiration group than that in aspiration group (P<0.05). There were the better survival functions without MACE in aspiration group than that of control group. Conclusion Thrombus aspiration, as an adjunctive method to primary PCI for STEMI, may improve TIMI flow, have beneficial effects on LVEF and reduce the incidence of recurrent angina at 12-month follow up.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects