Cardiac functional alterations and its risk factors in elderly patients with obstructive sleep apnea syndrome free of cardiovascular disease / 南方医科大学学报

OBJECTIVE@#To evaluate the changes of cardiac structure and function and their risk factors in elderly patients with obstructive sleep apnea syndrome (OSA) without cardiovascular complications.@*METHODS@#Eighty-two elderly OSA patients without cardiovascular disease admitted between January, 2015 and October, 2016 were enrolled in this study. According to their apnea-hypopnea index (AHI, calculated as the average number of episodes of apnoea and hypopnoea per hour of sleep), the patients were divided into mild OSA group (AHI < 15) and moderate to severe OSA group (AHI ≥ 15). The demographic data and the general clinical data were recorded and fasting blood samples were collected from the patients on the next morning following polysomnographic monitoring for blood cell analysis and biochemical examination. Echocardiography was performed within one week after overnight polysomnography, and the cardiac structure, cardiac function and biochemical indexes were compared between the two groups.@*RESULTS@#Compared with those with mild OSA group, the patients with moderate to severe OSA had significantly higher hematocrit (0.22±0.08 @*CONCLUSIONS@#Cardiac diastolic function impairment may occur in elderly patients with moderate or severe OSA who do not have hypertension or other cardiovascular diseases, and the severity of the impairment is positively correlated with AHI.

Correlation between severity of obstructive sleep apnea syndrome and red cell distribution width in elderly patients / 南方医科大学学报

OBJECTIVE@#To investigate the correlation between the severity of obstructive sleep apnea syndrome (OSAS) and red cell distribution width (RDW) in elderly patients.@*METHODS@#A cross-sectional study was conducted among 311 elderly patients diagnosed with OSAS in the snoring clinic between January, 2015 and October, 2016 and 120 healthy controls without OSAS from physical examination populations in the General Hospital of PLA. The subjects were divided into control group with apnea-hypopnea index (AHI) <5 (=120), mild OSAS group (AHI of 5.0-14.9; =90), moderate OSAS group (AHI of 15.0-29.9; =113) and severe OSAS group (AHI ≥ 30; =108). The clinical characteristics and the results of polysomnography, routine blood tests and biochemical tests of the subjects were collected. Multiple linear regression analysis was used to examine the correlation between OSAS severity and RDW.@*RESULTS@#The levels of RDW and triglyceride were significantly higher in severe OSAS group than in the other groups ( < 0.01). The levels of fasting blood glucose and body mass index were significantly higher in severe and moderate OSAS groups than in mild OSAS group and control group ( < 0.05 or < 0.01). Multiple linear regression analysis showed that AHI was positively correlated with body mass index (β=0.111, =0.032) and RDW (β=0.106, =0.029). The area under ROC curve of RDW for predicting the severity of OSAS was 0.687 (=0.0001).@*CONCLUSIONS@#The RDW increases as OSAS worsens and may serve as a potential marker for evaluating the severity of OSAS.

Research progress of nanomedicine in pediatric lung diseases / 中国药科大学学报

@#Nanomedicine is charactered with a high specific surface area, diversified structure and function, and charged surface. It can realize the targeted therap by functional modification of surface or introducing the stimuli-responsive unit. Therefore, nanomedicine is increasingly being concerned. Because nanomedicine can accumulate efficiently in the lungs, drug delivery systems based on nanotechnology have broad prospects in the field of the diagnosis, prevention, and treatment in pediatric lung diseases. Herein, we reviewed the research progress of nanomedicine in pediatric lung diseases, especially in respiratory syncytial virus infection and cystic fibrosis.

Erratum: Author correction to 'Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer' Acta Pharmaceutica Sinica B 2019; 9(5):1061-1077

[This corrects the article DOI: 10.1016/j.apsb.2019.03.006.].

Actively priming autophagic cell death with novel transferrin receptor-targeted nanomedicine for synergistic chemotherapy against breast cancer

Recently, considerable attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which could result in autophagic cell death (ACD). Though novel combination chemotherapy of autophagy inducers with chemotherapeutic agents is extensively investigated, nanomedicine-based combination therapy for ACD remains in infancy. In attempt to actively trigger ACD for synergistic chemotherapy, here we incorporated autophagy inducer rapamycin (RAP) into 7pep-modified PEG-DSPE polymer micelles (7pep-M-RAP) to specifically target and efficiently priming ACD of MCF-7 human breast cancer cells with high expression of transferrin receptor (TfR). Cytotoxic paclitaxel (PTX)-loaded micelle (7pep-M-PTX) was regarded as chemotherapeutic drug model. We discovered that with superior intracellular uptake and more tumor accumulation of micelles , 7pep-M-RAP exhibited excellent autophagy induction and synergistic antitumor efficacy with 7pep-M-PTX. Mechanism study further revealed that 7pep-M-RAP and 7pep-M-PTX used in combination provided enhanced efficacy through induction of both apoptosis- and mitochondria-associated autophagic cell death. Together, our findings suggested that the targeted excess autophagy may provide a rational strategy to improve therapeutic outcome of breast cancer, and simultaneous induction of ACD and apoptosis may be a promising anticancer modality.

Effects of co-administration with morin and acetyl-resveratrolon pharmacokinetics of saquinavir in rats / 中国药理学通报

Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats.Methods Twenty rats were randomized into four groups of equal size, including a control group, two intervention groups and a positive control group, and administered orally 30 mg·kg-1 SQV with or without 40 mg·kg-1 morin or acetyl-resveratrol or verapamil (as positive control).The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the PK of SQV was assessed using non-compartmental analysis.Results The PK parameters values of SQV, SQV+morin, SQV+acetyl-resveratrol, SQV+verapamil were as follows: AUC0-t, 381.53 μg·h·L-1,185.53 μg·h·L-1, 360.43 μg·h·L-1, 529.95 μg·h·L-1;AUC0-∞, 409.48 μg·h·L-1, 228.52 μg·h·L-1,446.67 μg·h·L-1, 552.41 μg·h·L-1;Cmax, 110.80 μg·L-1, 86.44 μg·L-1, 139.84 μg·L-1, 423.60 μg·L-1;Tmax, 0.25 h, 0.25 h, 0.25 h, 0.50 h;T1/2, 5.72 h, 5.94 h, 6.78 h, 3.78 h;MRT0-∞, 10.30 h, 9.61 h, 12.30 h, 4.89 h;CL/F, 7.59 mL·kg-1·h-1, 13.88 mL·kg-1·h-1, 7.28 mL·kg-1·h-1, 5.52 mL·kg-1·h-1.Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles.Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.

RhGLP-1 (7–36) protects diabetic rats against cerebral ischemia-reperfusion injury via up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD

The present study aimed to explore the neuroprotective effect and possible mechanisms of rhGLP-1 (7–36) against transient ischemia/reperfusion injuries induced by middle cerebral artery occlusion (MCAO) in type 2 diabetic rats. First, diabetic rats were established by a combination of a high-fat diet and low-dose streptozotocin (STZ) (30 mg/kg, intraperitoneally). Second, they were subjected to MCAO for 2 h, then treated with rhGLP-1 (7–36) (10, 20, 40 µg/kg i.p.) at the same time of reperfusion. In the following 3 days, they were injected with rhGLP-1 (7–36) at the same dose and route for three times each day. After 72 h, hypoglycemic effects were assessed by blood glucose changes, and neuroprotective effects were evaluated by neurological deficits, infarct volume and histomorphology. Mechanisms were investigated by detecting the distribution and expression of the nuclear factor erythroid-derived factor 2 related factor 2 (Nrf2) in ischemic brain tissue, the levels of phospho-PI3 kinase (PI3K)/PI3K ratio and heme-oxygenase-1 (HO-l), as well as the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA). Our results showed that rhGLP-1 (7–36) significantly reduced blood glucose and infarction volume, alleviated neurological deficits, enhanced the density of surviving neurons and vascular proliferation. The nuclear positive cells ratio and expression of Nrf2, the levels of P-PI3K/PI3K ratio and HO-l increased, the activities of SOD increased and the contents of MDA decreased. The current results indicated the protective effect of rhGLP-1 (7–36) in diabetic rats following MCAO/R that may be concerned with reducing blood glucose, up-regulating expression of Nrf2/HO-1 and increasing the activities of SOD.

Introduction of Applying for“Pharmacists’Health Care Provider Status”in the United States and Its En-lightenment on Clinical Pharmacist Legal System Construction in China / 中国药房

OBJECTIVE:To provide reference for the development of clinical pharmacists’career and the establishment of le-gal system in China. METHODS:The background,progress and situation of applying for“pharmacists’health care provider sta-tus”in the United States were introduced. The reasons for achieving provider status in California,Washington,and Oregon were summed up in aspects of politics,economics and education. The chance and challenge for achieving provider status at federal level were also discussed. Based on the development of clinical pharmacists in China,the suggestions were put forward for the improve-ment of legal system of clinical pharmacists in China. RESULTS & CONCLUSIONS:“Health care provider status”in the United Stated were recognised by 3 states with local developed economics,high-level education,and collective efforts of pharmacy organi-zations. Multiple national pharmacy organizations as American Pharmacists Association,American Society of Health-System Phar-macists and American Pharmacy College Society are working together toward provider status at the federal level. Our country should pay attention to related legal system construction,establish perfect and definite clinical pharmacists legal system as soon as possible to provide legal guarantee for career development of clinical pharmacists in China.

Influence of fluoxertin on level of IL-2,IL-6 and TNF-αin brain tissue and serum of rats with post-stroke depression / 重庆医学

Objective To explore the influence of fluoxertin on level of IL-2 ,IL-6 and TNF-α in brain tissue and serum of rats with post-stroke depression(PSD) .Methods 60 rats were divided into sham operation group ,depression group ,stroke group ,PSD group and fluoxertin group ,12 cases in each group .ELISA was used to detect the level of IL-2 ,IL-6 and TNF-αin brain tissue and serum .Results The level of IL-2 ,IL-6 and TNF-αin depression group ,stroke group and PSD group were significantly increased and higher than that in sham operation group and fluoxertin group(P0 .05) .Conclusion Fluoxertin could significantly decrease the level of IL-2 ,IL-6 and TNF-αand play an important role in therapy of PSD .

Effect of JPHSKL on the quantity of 5-Hydroxytryptamine of colonic mucosa of diarrhea-predominant irritable bowel syndrome rats / 重庆医学

Objective To observe the effect of Jian Pi Hua Shi Ke Li(JPHSKL) on IBS‐D ,gastrointestinal peptide hormones of rats 5‐HT ,and explore the therapeutic mechanism .Methods 60 clean‐level Wistar rats were used in the experiment .The rats were randomly divided into normal group ,model group ,JPHS low ,middle ,high and Deshute group(10 rats in each group) .Used gavage senna and restraint stress to establish D‐IBS rat model .The drug contrations of JPHSKL low ,midle ,high group were 1 .5 ,2 .5 ,4 .0 g/mL ,3 mg/mol in Deshute group .Once each day ,for 2 weeks ,the other groups were nomol group without any treatment and mod‐el group which building successful .Immunohistochemical SABC method to observe 5‐HT level of colonic specimens .Results The 5‐HT level in colonic tissue of the rats in IBS‐D model were obviously higher than the nomal group(P0 .05) .Conclusion JPHSKL can im‐prove gastrointestinal function of IBS‐D model rats ,effect mechanism is relating to decrease the level of 5‐HT in colonic mucosa .

Molecular biological research on Borna disease virus infection in depressive patients of Chongqing / 中国神经精神疾病杂志

Background Evidences, from recent studies, suggested that Borna disease virus (BDV) infection might be associated with human neuropsychosis, especially psychiatric disorders including depressive disorder(DD). However, controversy existed about the association between BDV infection and pathogenesis of DD. This study was to explore further whether the infection of Borna disease virus (BDV) is associated with the pathogenesis of depressive disorder (DD).Methods The p 24 fragment of BDV RNA in peripheral blood mononuclear cells (PBMCs) from 60DD patients and 120 healthy volunteers was detected by nested reverse transcriptase polymerase chain reaction (nRT-PCR) combined with fluorescence quantitative polymerase chain reaction (FQPCR). Positive products were cloned and sequenced before being compared with Strain V and strain He/80, from humans and animals.Results The positive rate (5%, 3/60) of BDV p 24 in PBMCs from the DD patients was significantly higher than that (0%, 0/120) from healthy volunteers ( P＜0. 05). The gene sequence for the positive products showed BDV p 24 in PBMCs from DD patients in Chongqing was most homophylic with H1766 strain detected from iii horses (97.68%), with 2 situs mutations (nt 1675 T→C, nt 1678 C→T), and also similar to the standard strain V(96. 51%)and He/80(95.35 %), with basic exchanges limited to T- C and A→G.Conclusions There was BDV infection in the DD patients in China, which indicated that the pathogenesis of DD in human beings in Chongqing might be associated with the infection of BDV.

Protective effects of isoliensinine on acute lung injury and pulmonary fibrosis induced by paraquat / 中国药理学与毒理学杂志

AIM To evaluate the beneficial effects of isoliensinine on paraquat(PQ)-induced acute lung injury and pulmonary fibrosis and explore the mechanism of its action. METHODS PQ (45 mg·kg-1, ip)-induced acute lung injury and PQ (100 mg·kg-1, ig)-induced pulmonary fibrosis were prepared. At 8, 24 and 48 h after PQ administration, the effects of isoliensinine (20 mg·kg-1, ig, 3 times a day, from 24 h before PQ administration to the end of experiment) on activity of superoxide dismutase (SOD), alkaline phosphatase (ALP) and the content of malondialdehyde (MDA) in plasma and bronchoalveolar lavage fluid (BALF) of acute lung injury groups were evaluated respectively. On the 14 d following PQ ingestion, the effects of isoliensinine (10, 20 and 40 mg·kg-1, ig, twice a day, from 24 h before PQ administration to the end of experiment) on hydroxyproline content, transforming growth factor β1 (TGF-β1) and matrix metalloproteinase-2 (MMP-2) expressions and the histopathological changes in lung tissues of pulmonary fibrosis groups were observed. RESULTS In the acute lung injury model, isoliensinine (20 mg·kg-1) significantly increased SOD activity, and decreased MDA content and ALP activity, as well as ameliorated the histopathological damage of lung tissue compared with PQ group. However, the indexes mentioned above in isoliensinine alone group did not change obviously compared with normal saline group. In the pulmonary fibrosis model, isoliensinine (10, 20 and 40 mg·kg-1) resulted in a dose-dependent decrease of hydroxyproline content compared with PQ group [(2.11±0.21), (1.94±0.24) and (1.89±0.26), respectively, vs (2.44±0.33) mg·g-1 wet tissue]. The expressions of TGF-β1 and MMP-2 in the lung tissue of the isoliensinine 40 mg·kg-1+PQ group were significantly less than those of the PQ group. Furthermore, isoliensinine could improve the histopathological changes of fibrosis as comparison with PQ group. CONCLUSION Isoliensinine has protective effects on PQ-induced acute lung injury and pulmonary fibrosis.