Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

KCNH2 mutation c.3099_3112del causes congenital long QT syndrome type 2 with gender differences

Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.

Comparación de las estructuras de difusión de información errónea y verídica en las redes sociales durante una emergencia de salud pública / Contrasting Misinformation and Real-Information Dissemination Network Structures on Social Media During a Health Emergency

RESUMEN Objetivos. Elaborar un esquema operativo integral para detectar la información errónea principal sobre el zika distribuida en Twitter® en el 2016; reconstruir las redes por las que se difunde información mediante retuiteo; contrastar la información verídica frente a la errónea con diversos parámetros; e investigar cómo se difundió en las redes sociales la información errónea sobre el zika durante la epidemia. Métodos. Revisamos sistemáticamente los 5 000 tuits más retuiteados con información sobre el zika en inglés, definimos "información errónea" a partir de la evidencia, buscamos tuits que tuvieran información errónea y conformamos un grupo equiparable de tuits con información verídica. Elaboramos un algoritmo para reconstruir las redes de retuiteo de 266 tuits con información errónea y 458 tuits equiparables con información verídica. Calculamos y comparamos nueve parámetros para caracterizar la estructura de las redes a varios niveles, entre los dos grupos. Resultados. En los nueve parámetros se aprecian diferencias estadísticamente significativas entre el grupo de información verídica y el de información errónea. La información errónea en general se difunde mediante estructuras más sofisticadas que la información verídica. También hay una considerable variabilidad intragrupal. Conclusiones. Las redes de difusión de la información errónea sobre el zika en Twitter fueron sustancialmente diferentes que las de información verídica, lo cual indica que la información errónea se sirve de mecanismos de difusión distintos. Nuestro estudio permitirá formar una comprensión más holística de los desafíos que plantea la información errónea sobre salud en las redes sociales.

ABSTRACT Objectives. To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic. Methods. We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of "misinformation," identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups. Results. There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too. Conclusions. Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

Electroacupuncture alleviates inflammatory pain via adenosine suppression and its mediated substance P expression / A eletroacupuntura alivia a dor inflamatória por meio da supressão de adenosina e da expressão mediada de substância P

ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund's Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund's Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund's Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund's Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.

RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.

The application of magnetic resonance imaging-guided microwave ablation for lung cancer

Context: It is necessary to explore a minimally invasive, effective, and efficient treatment for those lung cancer patients who are poor candidates for surgery. Aim: This study aimed to investigate the application of microwave ablation (MWA) in the treatment of lung cancer. Settings and Design: A total of 43 patients with 44 pulmonary lesions were examined following identical procedures before being randomly divided into two groups. The experimental group consists of 17 patients with a total of 18 pulmonary lesions, while the control group consists of 26 patients with a total of 26 pulmonary lesions. Materials and Methods: The experimental group was treated using magnetic resonance imaging (MRI)-guided MWA while the control group was treated using computer tomography (CT)-guided MWA. A transverse relaxation time-turbo spin echo (T2-TSE) sequence was used for signal collection in the experimental group to determine puncture location and microwave needle position while T2-TSE, T1-turbo field echo, and diffusion-weighted MRI (DWI) sequences were used for timely efficacy evaluation. Whereas in the control group, CT axial scanning was performed to serve similar purposes. Statistical Analysis Used: A nonparametric Wilcoxon test, median (M [25%, 75%]). Results: All of the 44 lesions were successfully located on the first attempt. The mean time for scanning and locating lung lesions under MRI and CT guidance were 64.53 and 42.96 min, the mean times of positioning were 12 and 18 min, and the mean durations of MWA were 12.48 and 15.06 min, respectively. Conclusions: As a minimally invasive method for treating lung tumors, MRI-guided MWA requires fewer localization scans, a shorter MWA duration, no radiation, real-time observation of the curative effect, and it prevents overtreatment

Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Protection Effect of Exogenous Fibroblast Growth Factor 21 on the Kidney Injury in Vascular Calcification Rats / 中华医学杂志(英文版)

<p><b>Background</b>Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats.</p><p><b>Methods</b>The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) Vitamin D3 plus nicotine (VDN)-induced VC group, (3) FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases (ALPs) activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 (FGFR1) protein were measured by enzyme-linked immunosorbent assay (ELISA). The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining.</p><p><b>Results</b>The renal function impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% (34.750 ± 4.334 μmol/L vs. 27.630 ± 2.387 μmol/L) and 4.0% (7.038 ± 0.590 mmol/L vs. 6.763 ± 0.374 mmol/L; P < 0.01), respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% (P < 0.01) and 11.7% (P < 0.05) as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. ELISA assays showed that the expression of β-Klotho, a component of FGF21 receptor system, was increased in VDN-treated VC rats by 37.4% (6.588 ± 0.957 pg/mg vs. 9.054 ± 0.963 pg/mg; P < 0.01), indicating an FGF21-resistant state. Moreover, FGF21 treatment downregulated the level of β-Klotho in renal tissue by 16.7% (9.054 ± 0.963 pg/mg vs. 7.544 ± 1.362 pg/mg; P < 0.05). However, the level of FGFR1, the receptor of FGF21, kept unchanged under VDN and VDN plus FGF21 administration (0.191 ± 0.0376 ng/mg vs. 0.189 ± 0.032 ng/mg vs. 0.181 ± 0.034 ng/mg; P > 0.05).</p><p><b>Conclusions</b>In the present study, FGF21 was observed to ameliorate the kidney injury in VDN-induced VC rats. FGF21 might be a potential therapeutic factor in CKD by cutting off the vicious circle between VC and kidney injury.</p>

Effects of Panax japonicus hypolipidemic compound on non-alcoholic fatty liver disease in mice and its mechanism / 解放军医学杂志

Objective To investigate the effects of Panax japonicas hypolipidemic compound (ZDS) on the lipid metabolism and its possible mechanism in non-alcoholic fatty liver disease (NAFLD) mice induced by high sugar and fat diet.Methods The extracts of Panaax japonica rhizoma,Salviae Miltiorrhiz radix Et rhizoma and Crataegi Fructus were prepared,and ZDS compound was formulated according to their antioxidant activities.Forty SPF male Kunming mice were randomly divided into four groups (10 each):normal control group,model group,high-dose ZDS-treated group,and low-dose ZDS-treated group.In addition to the mice in normal control group were given conventional diet,the mice in other three groups were fed high-sugar high-fat diet.High-dose and low-dose ZDS-treated group were given 90mg/kg or 30mg/kg ZDS.After the treatment of five weeks,the histomorphology and lipid deposition of the liver were observed to confirm the establishment of mouse NAFLD model and the improvement of ZDS compound on lipid deposition.The relative expression of miR-34a,SIRT1,and lipid metabolism related genes (FASN,ACC1) was detected by RT-qPCR and RT-PCR.SIRT1 protein expression was detected by Western blotting.Results Compared with the normal group,the morphological results showed hepatic lipid accumulation in the model group was more serious,the levels of triglyceride (TG) and miR-34a in the liver tissue increased significantly (P＜0.05),the expression levels of SIRT1 decreased,and the gene of lipid metabolism such as FASN,ACC1 significantly increased (P＜0.05).However,compared with the model group,ZDS compound improve hepatic lipid accumulation,liver TG content significantly decreased (P＜0.05),liver tissue miR-34a,FASN and ACC1 expressions decreased,while SIRT1 expression increased (P＜0.05).The protein expression of SIRT1 was consistent with its mRNA expression.Conclusion ZDS compound can effectively improve liver cell steatosis through the miR-34a/SIRT 1 pathway involved in lipid metabolism regulation,thus providing a new idea for early intervention of NAFLD through traditional Chinese compound medicine.

Analysis of c-MET, ALK, ROS1 variants in non-small cell lung cancer and its clinical significance / 临床与实验病理学杂志

Purpose The aim was to examine c-MET,ALK,ROS1 variants in advanced non-small cell lung cancer (NSCLC) patients,and to analysis the association of c-MET,ALK,ROS1 variants with the clinical and pathological features.Methods The c-MET,ALK,ROS1 were detected by fluorescence in situ hybridization (FISH) in the 91 cases of NSCLC specimens.The correlation of c-MET gene amplification with clinicopathological features and the ALK,ROS1 fusions was analyzed.Results The positive rate of c-MET gene amplification was 8.79％ (8/91),the positive rates on male and female were 1.82％ and 19.4％,respectively.In ＜ 60-years-old and ≥60-years-old NSCLC patients,the positive rates were 7.5％ and 8.89％,resepectively.The positive rate was higher in stage Ⅲ than stage Ⅳ (9.62％ vs 7.69％),the c-MET gene amplification was detected in 9.2％ adenocarcinoma patients but none in squamous carcinoma patients.The detection rates of ALK fusions and ROS1 fusions were 10％ and 13.3％,respectively.One patient was detected the coexistence of MET with ROS1 fusion.Conclusion The c-MET gene amplification is correlated with gender,but not with age,histological types and clinical stages.C-MET amplification,ALK fusions and ROS1 fusions are almost no coexistence,but not completely mutually exclusive.To they knowledge,this is the first case report the coexistence of MET amplification with ROS1 fusion in NSCLC.

The relationship between the recurrence of benign paroxysmal positional vertigo and the level of bone mineral as well as estrogen in postmenopausal women / 中华耳鼻咽喉头颈外科杂志

Objective@#To investigate the relationship between the recurrence of benign paroxysmal positional vertigo(BPPV) and the levels of bone mineral density(BMD) and estrogen in postmenopausal women.@*Methods@#A total of 38 postmenopausal women with recurrent BPPV were recruited as study group, in the First Affiliated Hospital of Soochow University from December 2013 to June 2017. Meanwhile, 49 normal menopausal women were included as control. All patients were natural menopausal for over one year.The patients were diagnosed as BPPV based on results of Dix-Hallpike test and Roll-test, with at least two episodes of recurrent onset. In the subjects, BMD was measured by dual X-ray absorptiometry of lumbar vertebrae. Estrogen levels were obtained by testing serum estradiol (E2) levels in early morning fasting venous blood. In the present study, we compared the level of E2 and the value of BMD in two groups by SPSS 21.0. In the study group, patients with decreased BMD were divided into two groups: treatment and untreated group. The recurrence rate of BPPV was compared between the two groups within 12 months.@*Results@#①The averagel levels of E2 and BMD in the study group were (16.21±11.00)ng/L and -1.68±0.98) respectively, which were significantly lower than those in the control group (t value was 7.03 and 8.05 respectively, both P<0.05). The averagel levels of E2 and BMD incontrol group were(28.52±6.34)ng/L and -0.18±0.77 respectively. ②The number of patients with decreased BMD in the study group (30 cases) was more than that in control group (6 cases), and the difference was statistically significant (P<0.05). ③ The recurrence rate of BPPV in treatment group [17.6%(3/17)] was significantly lower than that of untreated group [61.5%(8/13)], and the difference was statistically significant (P<0.05).@*Conclusion@#Recurrent BPPV in postmenopausal women usually accompany with low levels of estrogen and BMD. Active treatment is helpful for their recurrence of BPPV.

Effects of different samples and methods on the determination of blood biochemical indexes in rats / 中国比较医学杂志

Objective To compare the effects of two different samples and different test methods on blood biochemical indexes and blood glucose values in rats. Methods Glucose levels in the serum and plasma samples were detected with a blood glucometer, and the biochemical parameters in the serum and plasma were determined by routine blood biochemistry. The data were statistically compared and analyzed to determine if there are some significant differences. Results Among the 19 biochemical indexes of serum and plasma specimens, nine parameters, i. e. , ALB, TP, ALP, CHOL,URIC,GLU,Mg,LD,Ca showed significant differences(P< 0. 05),while the other 10 indexes showed no significant difference (P> 0. 05). Different samples and different methods had significant differences in the detection of blood glucose (P< 0. 05). Conclusions Different method and samples impact on the detection of blood glucose and some other serum and plasma biochemical indexes.

Effects of different samples and methods on the determination of blood biochemical indexes in rats / 中国比较医学杂志

Objective To compare the effects of two different samples and different test methods on blood biochemical indexes and blood glucose values in rats. Methods Glucose levels in the serum and plasma samples were detected with a blood glucometer, and the biochemical parameters in the serum and plasma were determined by routine blood biochemistry. The data were statistically compared and analyzed to determine if there are some significant differences. Results Among the 19 biochemical indexes of serum and plasma specimens, nine parameters, i. e. , ALB, TP, ALP, CHOL,URIC,GLU,Mg,LD,Ca showed significant differences(P< 0. 05),while the other 10 indexes showed no significant difference (P> 0. 05). Different samples and different methods had significant differences in the detection of blood glucose (P< 0. 05). Conclusions Different method and samples impact on the detection of blood glucose and some other serum and plasma biochemical indexes.

CENP-A Regulates Chromosome Segregation during the First Meiosis of Mouse Oocytes / 华中科技大学学报（医学）（英德文版）

Proper chromosome separation in both mitosis and meiosis depends on the correct connection between kinetochores of chromosomes and spindle microtubules.Kinetochore dysfunction can lead to unequal distribution of chromosomes during cell division and result in aneuploidy,thus kinetochores are critical for faithful segregation of chromosomes.Centromere protein A (CENP-A) is an important component of the inner kinetochore·plate.Multiple studies in mitosis have found that deficiencies in CENP-A could result in structural and functional changes of kinetochores,leading to abnormal chromosome segregation,aneuploidy and apoptosis in cells.Here we report the expression and function of CENP-A during mouse oocyte meiosis.Our study found that microinjection of CENP-A blocking antibody resulted in errors of homologous chromosome segregation and caused aneuploidy in eggs.Thus,our findings provide evidence that CENP-A is critical for the faithful chromosome segregation during mammalian oocyte meiosis.

Analysis of early results of adult congenital heart disease underwent surgical correction / 中华胸心血管外科杂志

Objective To summarize 500 cases of surgical experience in restoration of adult congenital heart disease ( ACHD) treatment and early postoperative.Methods During January 2012 to December 2014 in Fuwai Hospital, 500 cases of ACHD treated by operation were chosen to collect the clinical data .We divided the groups according to whether the case was a complex malformation and whether the case had an ICU retention time is more than the 5 days.Results The average age was 35, the average weight was 59 kg.The operation average cardiopulmonary bypass(CPB) time was 102min.The average ICU treatment time was 2 days, the average duration of mechanical ventilation was 23 hours, 3 early deaths occurred.The complex malformation group had younger age and less weight than the simple malformation group , the complex malformation group had longer time of cardiopulmonary bypass time, aortic cross clamping time, mechanical ventilation time and ICU treatment time, had higher rate of complication and blood transfusion peri-operative period than the simple malformation group.(P<0.05) The group of ICU retention time less than 5 days had higher rate of the male proportion, had younger age and less weigh, had longer time of cardiopulmonary bypass time , mechanical ventilation time and ICU treatment time , had higher rate of complication and blood transfusion peri-operative period than the control group(P <0.01).Conclusion Although ACHD patients have long medical history and complicated pathological and physiological changes , when they get proper surgical operation and periopera-tive treatment, they should obtain satisfied effect.Professional medical team or organization service for the ACHD patient is very important and urgent to build.

Preparation of PLGA Nanoparticles Loading Tetrandrine and Its Release in Vivo / 医药导报

Objective To prepare the PLGA nanoparticles( NPs) loading tetrandrine, investigate in vitro drug release behavior. Methods Tetrandrine loaded PLGA NPs were prepared by the emulsion solvent diffusion method and the preparation process was optimized by changing the stabilizer concentration and emulsion energy. The drug loading and entrapment efficiency were studied to evaluate the drug-loading property.The influence of particles size and pH value of release media on drug release behavior was investigated. Results Nanoparticles in the mean size of(203.4±2.8)nm had spherical shape and showed negative surface charge.Drug loading and entrapment efficiency was(2.17±0.10)% and(67.88±4.27)%, respectively.Tet-PLGA NPs retarded drug release in vitro, the cumulative release percentage was increased with the particle size increasing and it in acidic release medium showed a higher drug release amount. Conclusion Tetrandrine loaded PLGA nanoparticles have good entrapment efficiency, uniform particle size and can retard drug release in vitro.

Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile / 华中科技大学学报（医学）（英德文版）

The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.

Analysis of clinical use of post-marketing hospital centralized monitoring of Xiyanping injection / 中国中药杂志

To assess the clinical use and occurrence of adverse reactions of Xiyanping injection, and to provide reference for rational drug use in the clinic. Based on hospital central monitoring method, the clinical data of Xiyanping injection in our hospital in 2014 was tracked and analyzed. A total of 848 inpatients were enrolled in this study. Among them, 39.9% were not in accordance with the medication purpose. In practice, the dose more than the limits prescribed by the instructions of child and adult were accounted for 1.72% and 6.62%, respectively; improper choice of solvent, accounting for 3.18%; both the choice of versus intravenous drip and aerosol inhalati administration route were reasonable; mixed with other drug, accounting for 2.24%. The incidence of ADR of Xiyanping injection was 0.12%, which showed good safety. Irrational use of Xiyanping injection existed in clinics, and the use should be strengthened and regulated. The manufacturer should improve the drug instruction of usage and dosage.

Preparation and in vitro evaluation of tetrandrine-loaded composite microspheres embedded with PLGA nanoparticles / 中国中药杂志

In this paper, we prepared a type of composite microspheres embedded with poly (lactic-co-glycolic acid) (PLGA) nanoparticles for efficient inhalation delivery of tetrandrine (Tet), which is a traditional Chinese medicine for anticancer, and studied its morphology, drug release profile, cytotoxicity and cellular uptake behavior. PLGA nanoparticles loading tetrandrine were prepared by emulsion solvent diffusion method, and composite microspheres were prepared by spray drying method with mannitol as matrix due to its osmotic effect. Scanning electronic microscopy, dynamic light scattering laser particle analyzer and confocal microscopy were applied to characterize the morphology and size of the microspheres. The drug loading rate, drug encapsulation efficiency and drug release properties were explored by RP-HPLC. The cytotoxicity in A549 cells between crude drug of Tet and Tet-loaded microspheres were compared by MTT assay. The cellular uptake behavior of microspheres in A549 cells was investigated using confocal laser scanning microscopy. The resultant microspheres were composed of 189 nm PLGA nanoparticles exhibited sizes ranging from 1 to 3 μm, with the highest deposition efficiency. The microspheres can easily be dissolved in a mimic lung environment and release redispersible PLGA nanoparticles. Compared with crude drug of Tet, Tet-loaded microspheres showed a certain sustained release property and higher cytotoxicity effect to A549 cells. The cellular uptake experiment demonstrated a higher excellent penetration ability of cells to nanoparticles and time-dependent uptake process. This study provides a basis for developing new inhalation therapies for lung cancer.

Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile / 华中科技大学学报（医学）（英德文版）

The effect of surface charges on the cellular uptake rate and drug release profile of tetran-drine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.

Analysis for the Complication and Prognosis of Modified Extended Morrow Procedure in Patients With Hypertrophic Obstructive Cardiomyopathy / 中国循环杂志

Objective: To summarize the major post-operative complication of modiifed extended Morrow procedure in patients with hypertrophic obstructive cardiomyopathy (HOCM) and to explore the major factors affecting its prognosis. Methods: We retrospectively analyzed 139 consecutive HOCM patients who received the procedure by same surgeon in our hospital from 2012-06 to 2014-07. There were 87 male and 52 female patients with the age of (10-67) years, body weightof (26-105) kg and pre-operative left ventricular outlfow tract peak gradient (LVOTPG) of (84.48 ± 44.75) mmHg. Concomitant operations were performed with known cardiac disease as necessary. Pre- and post-operative echocardiography, ECG and chest X-ray were examined to assess the adequacy of resection and mitral valve structure and function. Results: There was no peri-operative death. 73/139 (53%) patients received simple modiifed expanded Morrow procedure, the other 66 (47%) patients received concomitant surgery including 21 patients with coronary artery bypass grafting, 15 mitral valve plasty, 7 mitral valve replacement, 10 tricuspid valve plasty, 2 aortic valve replacement, 3 modiifed Maze procedure, 2 unblock of right ventricular outlfow tract, 2 sub aortic membrane resection, 1 ventricular aneurysm resection. The mechanical ventilation time was (24.05±36.74) hours, post-operative ICU and in-hospital stays were (2.85±3.18) days and (10.11±4.57) days; the complications included arrhythmia in 108 cases, pleural effusion in 25 cases, secondary intubation in 1 case, tracheotomy in 1 case, hemoifltration in 1 case, intra-aortic balloon pump in 1 case, back into ICU in 3 cases; no pneumothorax, secondary thoracotomy/operation. The post-operative left atrial diameter, LVOTPG, inter-ventricular septal thickness and LVEF were all decreased; mitral valve closed well or with mild regurgitation, systolic anterior motion (SAM) basically disappeared. The major factors for delayed ICU stay included age≥55 years, female, CPB time≥120 min, AOC time≥90 min, the patients combining with arrhythmia and right ventricular dysfunction. Late follow-up presented that the patients were almost without the symptoms, NYHA classiifcation at (I-II), no late death, complication or re-operation. Conclusion: Modified expand Morrow procedure has good surgical and short/late post-operative effects, concomitant operation does not increase the complication and mortality; correction of arrhythmia and improving right ventricular function at peri-operative period are important for treating the relevant patients.