Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C

Bioequivalence of norfloxacin tablets in Chinese Healthy volunteers under Fasting and Fed Condition / 中国临床药理学与治疗学

AIM: To compare the bioavailability of norfloxacin tablets produced by Zhejiang Pharmaceutical Co., Ltd with the original product BACCIDAL, and to evaluate bioequivalence of two formulations, a randomized, open, two-cycle, self-crossing trial in healthy Chinese population was designed. METHODS: Under fasting and fed conditions, healthy volunteers were given a single dose of norfloxacin test or reference tablets for 100 mg. Liquid chromatography-mass spectrometry (LC-MS/MS) method were used to determine drug concentration in the plasma taken at different time points before and after dosing. Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software. RESULTS: A total of 28 healthy volunteers were enrolled and completed the fasting test. The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: C

Application of SM-PCR to detect plasma ctDNA in the treatment of patients with ad-vanced lung adenocarcinoma / 中国肿瘤临床

Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.

Study on the possibility of hippocampus injury during whole brain radiotherapy for intracranial metastasis / 中国医师进修杂志

Objective To investigate the rate of hippocampus injury during whole brain radiotherapy for intracranial metastasis and explore the effect of whole brain radiotherapy in reducing the radiotherapy induced neurocognitive dysfunction of hippocampu and provide reference for the treatment of intracranial metastatic tumors. Methods The intracranial metastases in 123 patients from January 2015 to December 2016 were enrolled in this study. The MRI image data before and after radiotherapy were analyzed retrospectively.The anatomical position of tumor and the hippocampus in patients with intracranial metastasis was outlined.According to outlined position, the relationship between location of intracranial metastatic tumor and the hippocampus was analyzed, and the probability of the hippocampal damage by tumor radiotherapy was calculated in the treatment of intracranial metastatic brain. Neurocognitive dysfunction improvement by protective irradiation of hippocampus was compared between different radiotherapy methods. Results Four hundred and seventeen intracranial metastatic tumors were observed in 123 patients, among which the sites of 15 tumors(3.60%) were within the 5mm of hippocampus, the sites of 146 tumors(35.01%)were 5-10 mm from the hippocampus, and the sites of 256 tumors(61.39%) were beyond 10 mm of hippocampus. The distribution of 417 metastatic tumors in the brain was as followings: 137 tumors (32.85%) were in frontal lobe, 98 tumors(23.50%) were in temporal lobe, 59 tumors(14.15%)were in parietal lobe, 46 tumors(11.03%)were in occipital lobe, 41 tumors (9.83%) were in cerebellum and 36 tumors (8.63%) were in basal ganglia. Using helical tomotherapy, intracranial metastasis radiotherapy and volumetric modulated arc radiotherapy, the rate of patients with cognitive dysfunction induced by hippocampal injury was 1.96%(1/51), 10.26%(4/39)and 18.18% (6/33), and there was significant difference (χ2= 6.595, P = 0.000). Conclusions The hippocampus injury possibility is very small, when whole brain radiotherapy is used in the treatment of intracranial metastatic tumors. Avoiding the hippocampus in radiation therapy of intracranial metastasis has high feasibility, among which the helical tomotherapy can effectively reduce hippocampus injury and improve patients'cognitive function.

Application of PAP PCR to monitor plasma cfDNA in advanced non-small cell lung can-cer / 中国肿瘤临床

Objective:To explore the application of pyrophosphorolysis-activated polymerization(PAP)to monitor plasma cfDNA in ad-vanced non-small cell lung cancer(NSCLC).Methods:A total of 85 patients diagnosed with advanced NSCLC between March 2016 and June 2017 were enrolled in the present study. EGFR mutations in cfDNA extracted from the plasma were detected using PAP and ARMS-PCR technology.The concordance analysis of EGFR mutations involved plasma vs.tumor tissue and PAP vs.ARMS-PCR.Further-more,38 EGFR-positive patients were selected to monitor EGFR mutations with PAP.Results:No statistical differences in EGFR muta-tions were observed between plasma and tumor tissue(P=0.092),as well as PAP and ARMS-PCR(P=0.210).The detection rate of EGFR mutations in cfDNA was higher in the progressor than in the non-progressor(62.5% vs.21.3%,P<0.001).Conclusions:PAP can be used for detecting and monitoring EGFR mutations in cfDNA to predict disease progression.

Comparison of clinical efficacy of penehyclidine hydrochloride and atropine in the treatment of acute organophosphorus pesticide poisoning / 中国基层医药

Objective To compare the clinical effect of penehyclidine hydrochloride and atropine in the treatment of acute organophosphorus pesticide poisoning.Methods 86 patients with organophosphorus pesticide poisoning were selected and randomly assigned to the observation group and the control group according to the digital table,43 cases in each group.The two groups were given conventional treatment,while the control group was treated with atropine,the observation group was given penehyclidine hydrochloride.The disappearance time of main symptoms, rescue success rate and adverse reactions of the two groups were observed.Results After salvage treatment, the rescue success rate of the observation group was 97.8%,which of the control group was 88.4%,the difference was statistically significant (x2=1.433,P<0.05).The disappear time of M like symptoms,N like symptoms and central nervous system symptoms in the observation group was significantly shorter compared with the control group (all P<0.05).The number of drugs,dosage,cholinesterase recovery time and hospitalization time between the two groups had statistically significant differences (P<0.05).The incidence rates of blurred vision,restlessness,heart rate and urinary retention in the control group were significantly higher than those in the observation group (all P<0.05).Conclusion Penehyclidine hydrochloride for acute organophosphorus pesticide poisoning can significantly reduce the incidence of symptoms,shorten the disappearance time of symptoms,reduce hospitalization time,improve the efficacy of rescue,reduce the incidence of adverse reactions, it is safe,effective and has great clinical significance.

Radionuclide myocardial perfusion imaging with ATP intervention in the diagnosis of coronary heart disease: a Meta-analysis / 中华核医学与分子影像杂志

Objective To assess the clinical value of MPI with ATP intervention (ATP-MPI) in the diagnosis of coronary heart disease (CHD).Methods To collect published literatures on ATP-MPI studies for the diagnosis of CHD,the PubMed,the Excerpta Medica Database (EMbase),Chinese Biomedical Literature Database (CBMdis),Vip and China National Knowledge Infrastructure (CNKI) databases were searched with computer and manual method since the data were available until to 2014.According to the inclusion and exclusion criteria,the literatures were screened to extract data by two independent evaluators.Meta-analysis was conducted with Stata 12.0 software.Results A total of 11 studies involving 968 patients were included.In patient study,which included 9 literatures and 933 patients,the Se,Sp,LR+,LRand 95％ CI of ATP-MPI diagnosis of CHD were 0.89 (0.82-0.94),0.84 (0.74-091),6.00 (3.25-9.91),0.13 (0.07-0.22),respectively.The diagnostic odds ratio (DOR) was 45.04.The AUC of summary ROC (SROC) curve was 0.94.In the coronary artery study,which included 6 literatures and 1 079 coronary arteries,the Se,Sp,LR+,LR-and 95％ CI of ATP-MPI diagnosis of coronary stenosis were 0.83 (0.71-0.91),0.92 (0.86-0.95),10.00 (5.58-16.99),0.18 (0.09-0.34),respectively.The DOR was 53.24 and the SROC AUC was 0.94.Conclusion ATP-MPI has a significant value in the diagnosis of CHD.

The clinical analysis of 146 cases of solitary pulmonary nodules / 重庆医学

Objective To study the relationship between the clinical imaging manifestations and the judgement of benign and malignant of solitary pulmonary nodules (SPN) .Methods A retrospective analysis of 146 patients with SPN which confirmed by pathological diagnosis .According to SPN diameter all SPN were divided into three groups ,the number of SPN which diameter smal-ler than 0 .8 cm were 16 case ,> 0 .8 - 1 .5 cm were 41 cases ,> 1 .5 - 3 .0 cm were 89 cases .Collect patients′ age ,sex ,smoking his-tory ,clinical symptoms and imaging data ,and analyze its relationship with pathological results .Results All the 146 patients were pathological diagnosis ,benign in 52 cases (35 .6% ) ,malignant in 94 cases (64 .4% ) .As the diameter increases ,the malignant rate increased .There was statistical significance in benign and malignant lesions with smoking history and clinical symptoms (P< 0 . 05) .Whether SPN boundary is clear ,have lobulation ,burr ,pleural indentation syndrome and vessel convergence in benign and ma-lignant lesions were statistically significant (P< 0 .05) .Conclusion The feature size and imaging performance of SPN has important reference value for the judgement of benign and malignant .The positive intervention to SPN have great significance on improve sur -vival rate of lung cancer .

Comparison of three methods on bilateral proper digital nerve injuries for repairing severed fingers / 中华骨科杂志

Objective To compare the clinical efficacy of the nerve bow (digital nerve and cutaneous antebrachii later-als) with end-to-side neuroanastomosis and traditional end-to-end neuroanastomosis for repairing bilateral proper digital nerve inju-ries while replanting injured fingers. Methods A total of 57 patients with bilateral proper digital nerve injuries from March 2009 to September 2012 were retrospectively analyzed. The patients were divided into three groups according to different treatments:19 patients underwent nerve graft bow end-to-side neuroanastomosis. During operation, a cutaneous antebrachii laterals nerve was freed and obtained from the homolateral forearm, which were sutured with bilateral distal digital nerve end to end, then nerve bow was formed. The bilateral proximal ends of digital nerve were sutured end-to-side bow, respectively. 22 patients underwent digital nerve bow end-to-side neuroanastomosis. During operation, bilateral distal ends and proximal ends were sutured respectively;con-sequently, the distal and proximal nerve bows were formed. A cutaneous antebrachii laterals nerve was obtained from the homolat-eral forearm, then divided equally to 2 parts which were used to bridge the 2 nerve digital nerve bow end-to-side neuroanastomosis bows. 16 patients underwent nerve graft with end-to-end neuroanastomosis. The sensation of finger plup, two point discrimination and motion of joints were evaluated. Results All patients achieved primary healing of wound after operation, with 57 fingers re-covered uneventfully. In nerve graft bow end-to-side neuroanastomosis group, 18 patients were followed up for 3-15 months;the average result of sensation measurement was S3+;the average result of two point discrimination was 5.1±0.8 mm. In digital nerve bow end-to-side neuroanastomosis group, 19 patients were followed up for 4-15 months;the average result of sensation measure-ment was S3; the average result of two point discrimination was 6.3 ± 0.9 mm. In nerve graft with end-to-end neuroanastomosis group, 12 patients were followed up for 3-14 months;the average result of sensation measurement was S2, the average result of two point discrimination was 7.2±1.4 mm. According to total active motion scales, there had no difference in results of motion of joints in the 3 groups. Conclusion The nerve bow end-to-side neuroanastomosis is valuable method for repairing bilateral proper digi-tal nerve injuries at the same time, which can restore sensation of fingers.

Effects of Recombinant Human B-type Natriuretic Peptid on Oxygen Consumption in Acute Myocardial Infarction with Heart Failure / 天津医药

Objective To evaluate the impact of different doses of recombinant human B-type natriuretic peptid (rh-BNP) within the dosage of clinical rage on oxygen consumption during acute myocardial infarction (AMI) with heart failure (HF). Methods AMI-HF model of York pig was established by occluding coronary artery with balloon combined with in-jecting microthrombus. Then animals were randomized into rhBNP group and control group. Clinical dose of rhBNP ( 1.5μg/kg bolus followed by a continuous infusion with speed of 0.01, 0.02 and 0.03μg · kg-1 · min-1 for 60 minutes respectively in turn) was administrated in rhBNP group while equal volume of saline was given in the control group. Myocardial oxygen up-take (MOU) was measured by drawing blood from coronary artery and coronary sinus using a catheter. Coronary diameter was determined using quantitative coronary angiography. The observation points were at baseline (T0), instant after the mod-el establishment (T1), 60 min after continuous rhBNP infusion of 0.01, 0.02, 0.03μg·kg-1·min-1 (T2-T4) respectively. Re-sults Compared with the control group, pulmonary capillary wedge pressure, central venous pressure, heart rate, systolic blood pressure and MOU were significantly decreased after rhBNP administration. And cardiac output and coronary diame-ter were obviously increased with addition of rhBNP. There is a interaction of drug intervention and time. In rhBNP group, MOU was significantly decreased with drug administraion (T2-T4 vs T1,mL O2/L: 10.61 ± 0.35,9.85 ± 0.60,9.79 ± 0.31 vs 11.59 ± 0.37). Conclusion Intravenous administration of rhBNP in AMI-HF model could decrease MOU and PCWP while increase the cardiac output.

Hepatolenticular Degeneration Is Disease Due to Toxin-pathogen Invading Collaterals / 中华中医药杂志

Hepatolenticular degeneration,namely Wilson's disease,an autosomal recessive disorder of copper metabolism.The author of this article gave a definition to toxin-pathogen,discussed the basic concept of collaterals disease briefly.And pointed out that hepatolenticular degeneration is a disease due to toxin-pathogen invading collaterals,which was caused by disorder of copper metabolism.This can result in toxin stagnating in collaterals and stagnation of blood stasis in collaterals in the initial stage,and collaterals injured at last.To improve QI-blood circulation and regulate the function of zang fu is important in order to accelerate elimination of toxin and prevent copper from stagnating. Specific therapy vary according to different clinical symptoms,such as promoting blood circulation for removing obstruction in collaterals and clearing toxin, clearing heat-fire and clearing toxin and dispersing stagnated liver-qi for promoting bile flow et al.

Value of high-frequency ultrasound in diagnosing Duchenne muscular dystrophy / 中华超声影像学杂志

Objective To evaluate the value of high-frequency ultrasound for diagnosing Duchenne muscular dystrophy.Methods Eighty-one cases with Duchenne muscualr dystrophy were divided into four groups according to their age,age 3-7(13 cases),age 7-10 (30 cases), age 10-13 (30 cases),age 13-14 (8 cases). Twenty cases of healthy children, aged from 1 to 11 were chosed as controls. In all groups' buttock muscle,thigh and leg muscle were observed by high-frequency ultrasound longitudinally and horizontally.Results Gluteus atrophy and subcutaneous fat thickening were seen in age 3 patients,progressive subcutaneous fat thickening and progressive muscular atrophy of buttock,thigh and leg with age were proved.There were significantly differences among groups ( P