Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective To compare the effects of different doses of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet in the treatment of cough variant asthma(CVA)and the improvement of airway function and inflammatory factors.Methods Elderly patients with cough variant asthma were randomly divided into group A and group B.Both groups of patients received budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet.Group A was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),2 inhalation per time,twice a day;Group B was given budesonide and formoterol fumarate powder for inhalation,4 inhalation per time,twice a day;budesonide fumatrol inhalation powder mist for continuous treatment for 6 months,and montelukast sodium tablet 10 mg once a day for at least 3 months.The nighttime cough scores of the two groups were compared before treatment and after treatment.The percentage of forced expiratory volume in one second(FEV1)in the predicted value,the maximum mid expiratory flow(MMEF),the fractional exhaled nitric oxide(FeNO),interleukin-5(IL-5)and eosinophils were compared between the two groups.The incidence of adverse drug reactions and the recurrence rate within 1 year were compared between the two groups.Results A total of 45 cases were enrolled in both the group A and the group B.At 9 months after treatment,the nocturnal cough scores of the group A and the group B were(0.93±0.42)and(0.65±0.29)points,respectively;the percentage of FEV1 in the predicted value were(97.75±9.67)％and(100.93±11.06)％,respectively;the MMEF values were(2.81±1.04)and(3.08±1.09)L·s-1,respectively;the FeNO values were(18.94±9.75)and(15.94±7.96)ppb,respectively;the IL-5 levels were(10.88±7.06)and(8.11±5.56)pg·mL-1,respectively.The above indicators in group B showed statistically significant differences compared to group A(all P＜0.05).The total incidence of adverse drug reactions in group A and group B were 8.89％(5 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.The recurrence rates was 15.56％(7 cases/45 cases)and 13.33％(6 cases/45 cases),respectively.There was no statistically significant difference in the above indicators between group B and group A(all P＞0.05).Conclusion For elderly patients with CVA,higher dose of budesonide and formoterol fumarate powder for inhalation combined with montelukast sodium tablet can better improve cough symptoms,reduce the level of airway hyperresponsiveness and inflammatory factors,reduce the recurrence rate,and the patients are well tolerated.

Objective To observe the effects of budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol on lung function,inflammatory markers,and exercise tolerance in stable chronic obstructive pulmonary disease(COPD)patients.Methods Stable COPD patients were randomly divided into control group and treatment group.The treatment group inhaled budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol,1 shovel per time,twice a day,once in the morning and once in the evening;respiratory function exercise for 15 minutes each time,bid.The control group was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),1 shovel each time,bid.The respiratory function exercise method was the same as that of the treatment group.Both groups of patients were treated continuously for 3 months.Compare the clinical efficacy of two groups of patients after treatment,and compare the lung function[forced expiratory volume in one second(FEV1),percentage of FEV1 to expected value(FEV,％),FEV1/forced vital capacity(FVC)],inflammatory indicators[interleukin-6(IL-6),IL-10],immune function indicators[T lymphocyte subsets(CD3+CD4+,CD8+),CD4+/CD8+],exercise tolerance[6-minute walking distance(6MWD),peak oxygen uptake(VO2 peak),maximum metabolic equivalents(METs)],and safety evaluation.Results Fifty cases were enrolled in the treatment group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis;50 cases were enrolled in the control group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis.The total effective rates of the treatment group and the control group were 91.67％(44 cases/48 cases)and 75.00％(36 cases/48 cases),with significant difference(P＜0.05).After treatment,the FEV1 of the treatment group and the control group were(1.99±0.19)and(1.79±0.21)L,the FEV1％were(64.18±5.85)％and(59.81±5.02)％,the FEV1/FVC were 61.82±5.37 and 53.45±6.11,the IL-6 levels were(19.53±4.08)and(27.82±4.57)ng·L-1,the IL-10 levels were(22.49±3.71)and(17.69±3.05)ng·L-1,the CD3+levels were(67.11±5.09)％and(64.20±4.26)％,the CD4+levels were(38.76±2.89)％and(36.15±3.04)％,the CD8+levels were(27.28±2.35)％and(28.76±2.59)％,the CD4+/CD8+were 1.49±0.28and 1.30±0.22,the 6MWD were(421.07±31.46)and(391.89±30.44)m,the VO2peak were(20.22±1.47)and(17.66±1.41)mL·min-1·kg-1,the METs were 5.61±1.02 and 4.86±1.04,respectively,the differences were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group included palpitations and headache;the adverse drug reactions in the control group included palpitations,headache and hoarseness.The total incidences of adverse drug reactions in the treatment group and the control group were 6.25％(3 cases/48 cases)and 6.25％(3 cases/48 cases),without statistically significant difference(P＞0.05).Conclusion Budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with respiratory function exercise has significant therapeutic effects and good safety in stable COPD patients.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective To observe the effects of budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol on lung function,inflammatory markers,and exercise tolerance in stable chronic obstructive pulmonary disease(COPD)patients.Methods Stable COPD patients were randomly divided into control group and treatment group.The treatment group inhaled budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol,1 shovel per time,twice a day,once in the morning and once in the evening;respiratory function exercise for 15 minutes each time,bid.The control group was given budesonide and formoterol fumarate powder for inhalation(Ⅱ),1 shovel each time,bid.The respiratory function exercise method was the same as that of the treatment group.Both groups of patients were treated continuously for 3 months.Compare the clinical efficacy of two groups of patients after treatment,and compare the lung function[forced expiratory volume in one second(FEV1),percentage of FEV1 to expected value(FEV,％),FEV1/forced vital capacity(FVC)],inflammatory indicators[interleukin-6(IL-6),IL-10],immune function indicators[T lymphocyte subsets(CD3+CD4+,CD8+),CD4+/CD8+],exercise tolerance[6-minute walking distance(6MWD),peak oxygen uptake(VO2 peak),maximum metabolic equivalents(METs)],and safety evaluation.Results Fifty cases were enrolled in the treatment group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis;50 cases were enrolled in the control group,2 cases were dropped out,and ultimately 48 cases were included in the statistical analysis.The total effective rates of the treatment group and the control group were 91.67％(44 cases/48 cases)and 75.00％(36 cases/48 cases),with significant difference(P＜0.05).After treatment,the FEV1 of the treatment group and the control group were(1.99±0.19)and(1.79±0.21)L,the FEV1％were(64.18±5.85)％and(59.81±5.02)％,the FEV1/FVC were 61.82±5.37 and 53.45±6.11,the IL-6 levels were(19.53±4.08)and(27.82±4.57)ng·L-1,the IL-10 levels were(22.49±3.71)and(17.69±3.05)ng·L-1,the CD3+levels were(67.11±5.09)％and(64.20±4.26)％,the CD4+levels were(38.76±2.89)％and(36.15±3.04)％,the CD8+levels were(27.28±2.35)％and(28.76±2.59)％,the CD4+/CD8+were 1.49±0.28and 1.30±0.22,the 6MWD were(421.07±31.46)and(391.89±30.44)m,the VO2peak were(20.22±1.47)and(17.66±1.41)mL·min-1·kg-1,the METs were 5.61±1.02 and 4.86±1.04,respectively,the differences were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group included palpitations and headache;the adverse drug reactions in the control group included palpitations,headache and hoarseness.The total incidences of adverse drug reactions in the treatment group and the control group were 6.25％(3 cases/48 cases)and 6.25％(3 cases/48 cases),without statistically significant difference(P＞0.05).Conclusion Budesonide,glycopyrronium bromide and formoterol fumarate inhalation aerosol combined with respiratory function exercise has significant therapeutic effects and good safety in stable COPD patients.

Background: and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. Methods: In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). Results: Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. Conclusion This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

OBJECTIVE: To investigate the correlation between pretransplant serum ferritin (SF) level and prolonged or prolonged isolated thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 35 patients with PT after allo-HSCT were retrospectively analyzed, and 35 patients were matched according to age and sex as a controls from 424 allo-HSCT patients with normal platelet count. The serum ferritin level before the transplantation was analyzed. The potential risk factors were analyzed by chi-square test and Fisher's exact test as well as univariate and multivariate logistic regression. The survival curve was estimated by the Kaplan-Meier model to explore its clinical significance. In addition, ROC curve was used to verify the predictive power of SF. RESULTS: Compared with control group, the SF level in the PT group before transplantation significantly increased (P=0.001). Multivariate analysis results showed that SF level before transplantation was a risk factor for prolonged thrombocytopenia after HSCT, and patients with SF≥1000 ng / ml showed a higher risk of death (P=0.014). ROC curve showed that SF level could be used as a predictor of prolonged thrombocytopenia after allo-HSCT. CONCLUSION The SF level before allo-HSCT relates with occurrence and prognosis of PT in patients after allo-HSCT. Detection of SF level can provide guidance for the intervention of prolonged thrombocytopenia after HSCT.
Ferritins ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Thrombocytopenia ; Transplantation, Homologous

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Bridged Bicyclo Compounds, Heterocyclic ; Cord Blood Stem Cell Transplantation ; Demethylation ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Sulfonamides