Regulating PI3K/Akt Signaling Pathway by Traditional Chinese Medicine to Improve Cognitive Impairment： A Review / 中国实验方剂学杂志

Cognitive impairment refers to the abnormality of the hippocampus， cortex and other parts of the brain， which is manifested by the decline of cognitive abilities such as learning， memory and attention. With the increase in people's work pressure and bad living habits， the incidence of cognitive impairment is getting higher and higher， which seriously affects people's normal life. However， there are adverse reactions such as gastrointestinal reactions and extrapyramidal reactions in Western drug treatment for cognitive impairment. Therefore， the development of a drug with relatively minimal adverse reactions is of great significance. Traditional Chinese medicine （TCM） has the characteristics of "multi-component， multi-pathway and multi-target"， and the incidence of adverse reactions is relatively low. Studies have shown that the pathogenesis of cognitive impairment is closely related to oxidative stress， inflammation， apoptosis， autophagy and other processes of neurons in the cerebral cortex and hippocampus. Phosphatidylinositol 3-kinase （PI3K）-protein kinase B （Akt） signal pathway plays an important role in the transmission of intracellular and intracellular signals， and in the regulation of cellular inflammation， apoptosis， autophagy， etc. TCM monomers， TCM extracts， and TCM compounds exert anti-inflammatory， antioxidant， anti-apoptotic and autophagy regulation effects by regulating the PI3K/Akt signaling pathway to improve cognitive impairment. This review first summarized the composition and regulatory process of the PI3K/Akt signaling pathway， and then discussed the research progress on the improvement of cognitive impairment through the improvement of oxidative stress， inflammation， apoptosis and autophagy of neurons. Finally， the recent research status of the regulation of this signaling pathway by TCM extracts， TCM monomers and TCM compounds to improve cognitive impairment was summarized. This study provides a theoretical basis for the future study of new TCM related to cognitive impairment.

Association of Toll-like receptor 7, CTLA-4 gene polymorphisms with severe asthma / 公共卫生与预防医学

Objective To explore the association of Toll-like receptor 7, CTLA-4 gene polymorphisms and severe asthma. Methods From February 2018 to March 2020, 175 asthma patients admitted to the respiratory department of our hospital were selected as the research subjects (109 cases of mild disease and 66 cases of severe disease), and 248 cases of healthy people who were included in the outpatient physical examination of our hospital during the same period were selected as the normal control group. Toll-like receptor 7 and CTLA-4 gene polymorphisms in the above groups were determined, and the relationship between Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma was evaluated by calculating the odds ratio (OR) and 95% confidence interval(CI). The relationship between the genotypes of Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma were evaluated by logistic regression analysis. Results The proportion of TLR7 rs3853839 CC genotype, CTLA-4 rs231725 AA genotype, TLR7 rs3853839 C allele frequency and CTLA-4 rs231725 A allele frequency in severe asthma group and mild asthma group were higher than those in normal control group(P<0.05). The proportion of TLR7 rs3853839 CC genotype, the proportion of CTLA-4 rs231725 AA genotype, the frequency of TLR7 rs3853839 C allele, and the frequency of CTLA-4 rs231725 A allele in the severe asthma group were higher than those in the mild asthma group(P<0.05). TLR7 rs3853839 CC genotype (OR=10.32, 95%CI=5.59-23.89), CTLA-4 rs231725 AA genotype (OR=13.21, 95%CI=3.58-20.25), TLR7 rs3853839 C allele frequency (OR=11.32, 95% CI=4.25-21.14) and CTLA-4 rs231725 A allele frequency (OR=13.24, 95% CI=6.59-20.21) could increase the susceptibility to severe asthma(P<0.05). TLR7 rs3853839CC genotype, TLR7 rs3853839C allele frequency, CTLA-4 rs231725AA genotype and CTLA-4 rs231725A allele frequency were risk factors for severe asthma(P<0.05). Conclusion TLR7 rs3853839 CC genotype, TLR7 rs3853839 C allele frequency, CTLA-4 rs231725 AA genotype and CTLA-4 rs231725 A allele frequency are associated with the occurrence of severe asthma.

Spontaneous Hind Limb Paralysis Due to Acute Precursor B Cell Leukemia in RAG1-deficient Mice.

RAG1-deficient mice are a frequently used immunodeficient mouse strain lacking mature lymphocytes. Apart from an elevated risk for infections, no predispositions for diseases of this strain have been described so far. We here report a high incidence of spontaneous pro B cell leukemia resulting in hind limb paralysis in our colony of RAG1-deficient mice. At an age of 7-13 months, animals developed hind limb paralysis and rapid decrease of the overall health condition leading to the need of euthanasia. Histological and flow cytometric analyses as well as micro-computed tomography (micro-CT) scans revealed CD45+ CD19+ IgM- cell infiltrates in the spleen, the bone marrow, and the spinal canal. Monthly blood sampling and screening for CD19+ blast frequency in the peripheral blood was successfully established for monitoring of leukemia development before symptom onset. We conclude that facilities that breed RAG1-deficient mice should be aware of the risk of leukemia development in this strain and recommend to implement regular blood sampling for aged RAG1-deficient animals.

Detailed characterisation and evaluation of composite stiffener R-zones based on mono-pulse ultrasonic reflection behavior.

R-zones are important part of the skin-stiffener joint in composite panels. Owing to their complex geometric shapes, defect behaviour, and poor accessibility, it is difficult to perform non-destructive testing and evaluation of their defects. A new method based on reflection behaviour generated by mono-pulse ultrasonic (MU) waves in R-zones for characterising and evaluating their defects was developed. Specimens with artificial and actual delaminations were used. The MU reflection behaviours, time-domain signals, and image characteristics originating from the R-zones were studied. Optical microscopy experiments were conducted to verify the MU results. Methods for discriminating the delamination and resin layer as well as determining their accurate depth were established using the MU signals from the R-zones. The experimental results show that delamination, resin layer, and pockets in the R-zones can be characterised and evaluated in detail using the MU method. Its resolution and dead zone reached 1 prepreg ply thickness. The minimum deviation of the layup depth of the detected delamination and resin layer in the R-zone is less than one prepreg ply thickness. Delaminations of ∅ 3 mm at different depths were detected reliably.

Quantification of Nerve Viscosity Using Shear Wave Dispersion Imaging in Diabetic Rats: A Novel Technique for Evaluating Diabetic Neuropathy

Objective@#Viscoelasticity is an essential feature of nerves, although little is known about their viscous properties. The discovery of shear wave dispersion (SWD) imaging has presented a new approach for the non-invasive evaluation of tissue viscosity.The present study investigated the feasibility of using SWD imaging to evaluate diabetic neuropathy using the sciatic nerve in a diabetic rat model. @*Materials and Methods@#This study included 11 diabetic rats in the diabetic group and 12 healthy rats in the control group.Bilateral sciatic nerves were evaluated 3 months after treatment with streptozotocin. We measured the nerve cross-sectional area (CSA), nerve stiffness using shear wave elastography (SWE), and nerve viscosity using SWD imaging. The motor nerve conduction velocity (MNCV) was also measured. These four indicators and the histology of the sciatic nerves were then compared between the two groups. The performance of CSA, SWE, and SWD imaging in distinguishing the two groups was assessed using receiver operating characteristic (ROC) analysis. @*Results@#Nerve CSA, stiffness, and viscosity in the diabetic group was significantly higher than those in the control group (all p < 0.05). The results also revealed a significantly lower MNCV in the diabetic group (p = 0.005). Additionally, the density of myelinated fibers was significantly lower in the diabetic group (p = 0.004). The average thickness of the myelin sheath was also lower in the diabetic group (p = 0.012). The area under the ROC curve for distinguishing the diabetic neuropathy group from the control group was 0.876 for SWD imaging, which was significantly greater than 0.677 for CSA (p = 0.030) and 0.705 for SWE (p = 0.035). @*Conclusion@#Sciatic nerve viscosity measured using SWD imaging was significantly higher in diabetic rats. The viscosity measured using SWD imaging performed well in distinguishing the diabetic neuropathy group from the control group.Therefore, SWD imaging may be a promising method for the evaluation of diabetic neuropathy.

Effect of general anesthesia guided by electroencephalography monitoring on postoperative delirium in elderly patients with non-acute fragile brain function / 中华麻醉学杂志

Objective:To evaluate the effect of general anesthesia guided by electroencephalography (EEG) monitoring on postoperative delirium (POD) in elderly patients with non-acute fragile brain function.Methods:Sixty patients of both sexes with non-acute fragile brain function, aged 65-85 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 18-30 kg/m 2, undergoing hip replacement, were divided into 2 groups ( n=30 each) by a random number table method: conventional general anesthesia group (group C) and general anesthesia guided by EEG monitoring group (group E). Anesthesia was maintained by intravenous infusion of propofol 50-150 μg·kg -1·min -1 and remifentanil 0.05-0.30 μg·kg -1·min -1 and intermittent intravenous boluses of rocuronium.In group E, the dose of anesthetic was reduced when the EEG burst-suppression ratio≥10% for more than 1 min or anesthesia index (AI) <40.If the situation mentioned above still existed after 1 min, the dose of anesthetic was continued to be reduced or norepinephrine was injected intravenously.In group C, the amount of intraoperative anesthesia was adjusted according to the changes in hemodynamics.Norepinephrine 4-10 μg or dopamine 1 mg was given intravenously in the light of the patients′ heart rates when intraoperative hypotension occurred.At 10 min after anesthesia induction, immediately after skin incision, immediately at the end of surgery and at 1 h after surgery, blood samples were obtained from the artery and jugular venous bulb for blood gas analysis and for calculation of jugular bulb blood oxygen content (CjvO 2), artery-jugular bulb blood oxygen content difference (Ca-jvO 2), cerebral oxygen uptake rate (CERO 2) and jugular-arterial blood lactate concentration difference (Djv-aLac). The emergence time, amounts of intraoperative anesthetics, use of noradrenaline, cumulative time of EEG burst inhibition and duration of AI<40 were recorded.The development of POD was assessed within 5 days after surgery by the confusion assessment method for the intensive care unit and the duration was recorded. Results:Compared with group C, recovery time, cumulative time of EEG burst inhibition and duration of AI<40 were significantly shortened, the intraoperative consumption of propofol and remifentanil was decreased, the requirement for intraoperative noradrenaline was increased, CjvO 2 was increased, Ca-jvO 2 and CERO 2 were decreased immediately at the end of surgery and at 1 h after surgery, the incidence of POD within 5 days after surgery was decreased, and POD duration was shortened in group E ( P<0.05). Conclusion:General anesthesia guided by EEG monitoring can reduce the development of POD in elderly patients with non-acute fragile brain function.

Association between exposure to ambient air pollution and hospital admission, incidence, and mortality of stroke: an updated systematic review and meta-analysis of more than 23 million participants

BACKGROUND@#Previous studies have suggested that exposure to air pollution may increase stroke risk, but the results remain inconsistent. Evidence of more recent studies is highly warranted, especially gas air pollutants.@*METHODS@#We searched PubMed, Embase, and Web of Science to identify studies till February 2020 and conducted a meta-analysis on the association between air pollution (PM@*RESULTS@#A total of 68 studies conducted from more than 23 million participants were included in our meta-analysis. Meta-analyses showed significant associations of all six air pollutants and stroke hospital admission (e.g., PM@*CONCLUSIONS@#Exposure to air pollution was positively associated with an increased risk of stroke hospital admission (PM

Acute effect of ambient fine particulate matter on heart rate variability: an updated systematic review and meta-analysis of panel studies

BACKGROUND@#Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 μm in diameter (PM@*METHODS@#An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM@*RESULTS@#A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 μg/m@*CONCLUSION@#Short-term exposure to PM

Research and treatment progress of acute lymphoblastic leukemia with NOTCH1 gene mutation / 中国基层医药

T-cell acute lymphonlastic leukemia(T-ALL) is one of the common hematological malignancies in children and adolescents, and it has a rapid progress and high mortality.Since the first activated mutation in NOTCH1 was found in T-ALL with t(7; 9) translocation in 1991.The pathogenesis and clinical treatment of NOTCH1 gene mutation and T-ALL had made some progress at subsequent years.However, there are still some differences in the prognosis of children and adults after using chemotherapy drugs.Therefore, the differences of prognosis of acute lymphoblastic leukemia with NOTCH1 gene mutation in adults and children and the latest treatment progress are reviewed and hope to provide guidance for clinical treatment.

Clinical efficacy of combined or single use of clofibrate and cytarabine in treatment of adult patients with myelodysplastic syndromes or acute leukemia: a Meta analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy of combined or single use of clofibrate and cytarabine in the treatment of adult patients with myelodysplastic syndromes (MDS) or acute leukemia (AL).Methods Clofarabine combined with cytarabine was used in the combined group and clofarabine or cyarabine alone was used in the control group.All the studies about cytarabine and clofarabine were searched in PubMed,Cochrance Library,Embase,CNKI,Wanfang and VIP database by computer,and then the data was extracted.Results The complete remission rate of the combined group was higher than that of the control group [33.1％ (93/281) vs.18.2％ (35/192),and the difference was statistically significant (RR =1.85,95％ CI 1.31-2.60,P ＜ 0.01).The overall response rate of the combined group was higher than that of the control group [44.0％ (124/282) vs.23.2％ (46/198)],and the difference was statistically significant (RR =1.92,95％ CI 1.44-2.56,P ＜ 0.01).However,the incidence of skin adverse reactions in the combined group was also higher than that in the control group [38.8％ (104/268) vs.3.1％ (6/192)],and the difference was statistically significant (RR =7.76,95％ CI 3.68-16.38,P ＜ 0.01).Conclusion The combination of clofarabine and cytarabine in the treatment of adult patients with MDS or AL has better clinical efficacy than single application,but it also has more serious skin adverse reactions.

Efficacy of rituximab combined with cyclophosphamide and fludarabine in treatment of chronic lymphocytic leukemia: a Meta-analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL). Methods FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software. Results A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant ( RR＝1.89, 95% CI 1.64-2.18, P<0.01; RR＝1.15, 95% CI 1.10-1.21, P<0.01). In terms of gradeⅢ-Ⅳadverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant ( RR＝1.25, 95% CI 1.01-1.55, P＝0.004). Conclusion The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳneutropenia.

Advances in the role of latent membrane protein 1 in hematological tumors and its mechanism / 白血病·淋巴瘤

Latent membrane protein 1 (LMP1) as a product of human herpesvirus 4 encoding is closely related to the occurrence and development of various tumors. However, the articles related to hematological tumors are rare. This review focuses on the correlation between LMP1 and hematological tumors and the progress of treatment.

Efficacy and safety of thalidomide combined with VAD regimen in treatment of multiple myeloma: a Metaˉanalysis of Chinese literature / 白血病·淋巴瘤

Objective To analyze the clinical efficacy and safety of thalidomide combined with VAD regimen (vincristine+epirubicin+dexamethasone) or VAD regimen alone in treatment of multiple myeloma (MM) by using metaˉanalysis. Methods Thalidomide combined with VAD regimen was selected as the experimental group and VAD regimen alone was selected as the control group. The literatures were searched from CNKI, Wanfang and VIP database. And then the inclusive literatures were further searched. Randomized controlled trials eligible to the exclusive criteria were extracted, and the quality was evaluated. Metaˉanalysis was conducted by using Stata14.0 software. Results A total of 17 studies and 940 patients were included. The experimental group had a higher total effective rate compared with the control group , and the difference was statistically significant ( RR＝ 1.41, 95% CI 1.30-1.59, P< 0.01). Meanwhile, the experimental group had a better efficacy in improving hemoglobin and deducing βˉmacroglobulin (MG), M protein and myeloma cells compared with the control group; however, the experimental group also had a worse gastrointestinal reaction, and the difference was statistically significant ( RR＝ 1.36, 95% CI 1.04-1.78, P＝ 0.024). Conclusion Thalidomide combined with VAD regimen in treatment of MM has a better clinical efficacy compared with VAD regimen alone, but it also has a worse adverse reaction.

Meta analysis of clinical efficacy of fluconazole combined with clotrimazole in the treatment of candida vaginitis / 中国基层医药

Objective To OxplorO thO clinical Officacy of oral fluconazolO combinOd with clotrimazolO vaginal administration in thO trOatmOnt of candida vaginitis by mOta analysis. Methods FluconazolO combinOd with clotrima-zolO was sOlOctOd as OxpOrimOnt group and clotrimazolO alonO was sOlOctOd as control group. ThO randomizOd controllOd trials( RCTs) wOrO rOtriOvOd from PubMOd, CochranO library, EmbasO, China Notional KnowlOdgO infrastructurO (CNKI), WangFang and VIP databasO and rOfOrOncOs listOd in all studiOs. RCTs mOOting inclusivO studiOs wOrO includOd, thO data wOrO OxtractOd, thO quality was OvaluatOd and cross - chOckOd by two rOviOws indOpOndOntly according to CochranO Handbook for SystOmatic ROviOws of IntOrvOntions and thOn MOta -analysis was conductOd using Stata14.0 softwarO. Results A total of 15 studiOs and 1 792 patiOnts wOrO includOd.ThO OxpOrimOnt group had a highOr ovOrall OfficiOncy(OxpOrimOnt group in 96.13% and control group in 83.8% ),thO diffOrOncO was statistically significant (RR=1.13,95% CI 1.08~1.18,P<0.001). ThO rOcurrOncO ratO aftOr trOatmOnt( OxpOrimOnt group in 6.46% and control group in 20.74% ) had statistically significant diffOrOncO bOtwOOn thO two groups ( RR=0.31, 95% CI 0.21~0.46,P<0.001).Conclusion MOta analysis showOd that oral fluconazolO combinOd with clotrima-zolO vaginal administration has a bOttOr clinical Officacy.

Efficacy of rituximab combined with cyclophosphamide and fludarabine in treatment of chronic lymphocytic leukemia: a Meta-analysis / 白血病·淋巴瘤

Objective@#To analyze the clinical efficacy and safety of fludarabine combined with cyclophosphamide (FC) and fludarabine and cyclophosphamide combined with rituximab (FCR) in the treatment of chronic lymphocytic leukemia (CLL).@*Methods@#FCR regimen was selected as the experimental group, and FC regimen was selected as the control group. The studies were retrieved from PubMed, Cochrane Library, Embase, CNKI, Wangfang and VIP databases by computer and the references listed in these studies were further searched. The randomized controlled trials (RCT) meeting inclusive criteria were extracted, and the quality was evaluated and cross-checked independently according to Cochrane Handbook for Systematic Reviews of Interventions, and then the Meta-analysis was conducted by using StataMP 14.0 software.@*Results@#A total of 7 studies and 1 985 patients were included. The complete remission rate and overall response rate of FCR regimen were better than those of FC regimen, and the differences were statistically significant (RR = 1.89, 95% CI 1.64-2.18, P < 0.01; RR = 1.15, 95% CI 1.10-1.21, P < 0.01). In terms of grade Ⅲ-Ⅳ adverse reactions, the neutropenia of FCR regimen was more severe than that of FC regimen, and the difference was statistically significant (RR = 1.25, 95% CI 1.01-1.55, P = 0.004).@*Conclusion@#The FCR regimen has a better clinical outcome and prognosis than the FC regimen, and is accompanied by more severe grade Ⅲ-Ⅳ neutropenia.

Clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia: a Meta analysis / 白血病·淋巴瘤

Objective@#To analyze the clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia by using Meta analysis.@*Methods@#Thalidomide combined with conventional chemotherapy was treated as the experiment group, chemotherapy alone was treated as the control group. Thalidomide was taken 100mg once a day, oral administration. The literatures were retrieved from PubMed, Cochrane library, Embase, China Notional Knowledge Infrastructure (CNKI),Wanfang and VIP database. The data of the randomized controlled trial (RCT) conformed to inclusion criteria were extracted, and the quality was evaluated, and then StataMP 14.0 software was used to make a Meta analysis.@*Results@#A total of 14 studies with 752 patients were included. The experiment group had a higher complete remission rate and the overall response rate compared with the control group, and the difference was statistically significant (RR= 1.61, 95% CI 1.36-1.90, P < 0.01; RR= 1.36, 95%CI 1.24-1.50, P < 0.01). The experiment group had a better efficacy in the improvement of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), basic fibroblast growth factor (bFGF) and bone marrow microvessel density (MVD) after the treatment compared with the control group, and the differences between the two groups were statistically significant (all P < 0.05), but there was no significant difference in the adverse events between the two groups (all P > 0.05).@*Conclusion@#Meta analysis showed that oral administration daily thalidomide 100 mg combined with conventional chemotherapy has a better clinical efficacy and antiangiogenic effect compared with chemotherapy alone, without the increase of adverse reactions.

Elderly hypertension patients with obstructive sleep apnea syndrome and heart rate and blood pressure variability and the intervention effects of home-based continuous positive airway pressure therapy / 中华老年医学杂志

Objective@#To study the correlation of the degree of sleep apnea with arrhythmia, heart rate variability(HRV)and blood pressure variability(BPV)in elderly patients with obstructive sleep apnea hypopnea syndrome(OSAHS), and to investigate the intervention effects of home-based continuous positive airway pressure(CPAP)treatment.@*Methods@#A total of 122 elderly hypertension patients with OSAHS were recruited in the prospective study.Patients were divided into three groups according to the sleep apnea hypopnea index(apnea hypopnea index, AHI): the mild OSAHS group(5 times/h≤AHI≤15 times/h, n=42), moderate OSAHS group(15 times/h<AHI≤30 times/h, n=40)and severe OSAHS group(AHI>30 times/h, n=40). All patients took ambulatory electrocardiogram and ambulatory blood pressure examinations before and after three months of CPAP treatment.The incidences of arrhythmia, HRV and BPV indexes of each group before and after CPAP treatment were compared between the groups.@*Results@#The incidences of premature atrial contraction, atrial tachycardia and premature ventricular beats were higher in the moderate and severe OSAHS groups than in the mild OSAHS group(P<0.01). Compared with the mild OSAHS group, the RR interval standard deviation(SDNN), root mean square of successive differences(rMSSD), proportion of patients with consecutive RR-interval differences greater than 50 ms(PNN5), standard deviation of the averaged normal RR intervals for all 5 min segments and deceleration capacity of rate increased in the moderate and severe OSAHS groups(P<0.05), and the increases were more obvious in the severe group.Compared with the mild OSAHS group, the standard deviation of 24-h systolic blood pressure, standard deviation of 24-h diastolic blood pressure, standard deviation of daytime systolic blood pressure, standard deviation of nighttime systolic blood pressure and incidence of non-dipper hypertension increased in the moderate and severe OSAHS groups(P<0.05), with the increases were more obvious in the severe group, and the differences was significant between the moderate and severe OSAHS groups(P<0.05). HRV and BPV indicators improved except for high frequency(HF)/low frequency(LF)in all groups(P<0.05)after home treatment of CPAP, and the improvement was more obvious in the severe group.The incidence of non-dipper circadian rhythm of blood pressure improved more significantly in the severe OSAHS group than in the moderate OSAHS group.@*Conclusions@#With aggravated sleep apnea, the incidences of arrhythmias such as premature atrial contraction, atrial tachycardia, and premature ventricular contraction are increased and the HRV and BPV are enlarged in elderly hypertension patients complicated with OSAHS.The home treatment of CPAP can improve the above indicators, and it is an effective way to treat OSAHS complicated by hypertension in elderly patients.

Elderly hypertension patients with obstructive sleep apnea syndrome and heart rate and blood pressure variability and the intervention effects of home-based continuous positive airway pressure therapy / 中华老年医学杂志

Objective To study the correlation of the degree of sleep apnea with arrhythmia,heart rate variability(HRV) and blood pressure variability(BPV)in elderly patients with obstructive sleep apnea hypopnea syndrome(OSAHS),and to investigate the intervention effects of home-based continuous positive airway pressure(CPAP)treatment.Methods A total of 122 elderly hypertension patients with OSAHS were recruited in the prospective study.Patients were divided into three groups according to the sleep apnea hypopnea index(apnea hypopnea index,AHI):the mild OSAHS group(5 times/h≤AHI≤15 times/h,n=42),moderate OSAHS group(15 times/h＜ AHI≤30 times/h,n=40) and severe OSAHS group (AHI＞30times/h,n=40).All patients took ambulatory electrocardiogram and ambulatory blood pressure examinations before and after three months of CPAP treatment.The incidences of arrhythmia,HRV and BPV indexes of each group before and after CPAP treatment were compared between the groups.Results The incidences of premature atrial contraction,atrial tachycardia and premature ventricular beats were higher in the moderate and severe OSAHS groups than in the mild OSAHS group(P＜0.01).Compared with the mild OSAHS group,the RR interval standard deviation(SDNN),root mean square of successive differences (rMSSD),proportion of patients with consecutive RR-interval differences greater than 50 ms (PNN5),standard deviation of the averaged normal RR intervals for all 5 min segments and deceleration capacity of rate increased in the moderate and severe OSAHS groups(P＜0.05),and the increases were more obvious in the severe group.Compared with the mild OSAHS group,the standard deviation of 24-h systolic blood pressure,standard deviation of 24-h diastolic blood pressure,standard deviation of daytime systolic blood pressure,standard deviation of nighttime systolic blood pressure and incidence of non-dipper hypertension increased in the moderate and severe OSAHS groups (P ＜ 0.05),with the increases were more obvious in the severe group,and the differences was significant between the moderate and severe OSAHS groups(P ＜0.05).HRV and BPV indicators improved except for high frequency(HF)/low frequency(LF) in all groups (P ＜ 0.05) after home treatment of CPAP,and the improvement was more obvious in the severe group.The incidence of non-dipper circadian rhythm of blood pressure improved more significantly in the severe OSAHS group than in the moderate OSAHS group.Conclusions With aggravated sleep apnea,the incidences of arrhythmias such as premature atrial contraction,atrial tachycardia,and premature ventricular contraction are increased and the HRV and BPV are enlarged in elderly hypertension patients complicated with OSAHS.The home treatment of CPAP can improve the above indicators,and it is an effective way to treat OSAHS complicated by hypertension in elderly patients.

Clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia: a Meta analysis / 白血病·淋巴瘤

Objective To analyze the clinical efficacy and safety of thalidomide combined with conventional chemotherapy in treatment of acute leukemia by using Meta analysis. Methods Thalidomide combined with conventional chemotherapy was treated as the experiment group, chemotherapy alone was treated as the control group. Thalidomide was taken 100mg once a day, oral administration. The literatures were retrieved from PubMed, Cochrane library, Embase, China Notional Knowledge Infrastructure (CNKI), Wanfang and VIP database. The data of the randomized controlled trial (RCT) conformed to inclusion criteria were extracted, and the quality was evaluated, and then StataMP 14.0 software was used to make a Meta analysis. Results A total of 14 studies with 752 patients were included. The experiment group had a higher complete remission rate and the overall response rate compared with the control group, and the difference was statistically significant (RR ＝ 1.61, 95% CI 1.36-1.90, P< 0.01; RR＝ 1.36, 95% CI 1.24-1.50, P< 0.01). The experiment group had a better efficacy in the improvement of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), basic fibroblast growth factor (bFGF) and bone marrow microvessel density (MVD) after the treatment compared with the control group, and the differences between the two groups were statistically significant (all P <0.05), but there was no significant difference in the adverse events between the two groups (all P＞0.05). Conclusion Meta analysis showed that oral administration daily thalidomide 100 mg combined with conventional chemotherapy has a better clinical efficacy and antiangiogenic effect compared with chemotherapy alone, without the increase of adverse reactions.

Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy

The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy.