Anaplastic lymphoma kinase (ALK) fusions represent the second most common oncogenic driver mutation in non-small cell lung cancer (NSCLC). As the new class of 3rd generation of ALK tyrosine kinase inhibitor (TKI), lorlatinib has shown robust potency and brain-penetrant clinical activity against a wide spectrum of multiple resistance mutations within the ALK domain detected during crizotinib and 2nd generation ALK TKI treatment. Lorlatinib is generally well-tolerated with unique adverse drug reaction/adverse event, including hyperlipidemia and central nervous system effects, which are mostly mild to moderate severity and manageable through dosage modifications and/or standard medical intervention. For advanced NSCLC with ALK positivity, patients should be evaluated for baseline characteristics and pre-existing medication, informed of the potential toxicities, and periodically monitored to balance benefits and risks. Moreover, a multidisciplinary group of experts is essential to establish a comprehensive diagnostic and therapeutic strategy.
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Aminopyridines ; Carcinoma, Non-Small-Cell Lung/pathology* ; China ; Consensus ; Drug Resistance, Neoplasm/genetics* ; Drug-Related Side Effects and Adverse Reactions/drug therapy* ; Humans ; Lactams ; Lactams, Macrocyclic/adverse effects* ; Lung Neoplasms/pathology* ; Protein Kinase Inhibitors/adverse effects* ; Protein-Tyrosine Kinases/genetics* ; Pyrazoles

Objective:To assess the value of 4-dimensional CT angiography (4D CTA) to predict hemorrhagic transformation (HT) with a new nomogram model in acute ischemic stroke (AIS) patients after endovascular treatment (EVT).Methods:Imaging and clinical data of 101 AIS patients with internal carotid artery and/or middle cerebral artery occlusion who underwent "one-stop" CTA-CT perfusion and EVT in green channel of Beijing Hospital from March 2016 to November 2020 were analyzed retrospectively. The patients were divided into HT group (45 patients) and non-HT group (56 patients). Multivariate logistic regression analysis was used to select relevant clinical and imaging variables, such as age, initial National Institute of Health stroke scale (NIHSS) score, 4D CTA collateral circulation score, Alberta stroke program early CT score (ASPECTS), clot burden score, and a predictive nomogram model were developed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the efficacy of predictive nomogram model for diagnosing HT.Results:Univariate analysis showed that there were significant difference of age[79.00(68.00, 85.00) years, 73.00(62.75, 80.00) years, Z=-2.20, P=0.028], NIHSS score [16.00(12.00, 21.00), 9.50(6.00, 14.00), Z=-4.44, P<0.001], ASPECTS score [5.00(3.00, 8.00), 8.00(7.00, 9.00), Z=-4.23, P<0.001], 4D CTA collateral circulation score [2.00(0, 3.00), 3.00(3.00, 4.00), Z=-5.39, P<0.001], clot burden score [4.00(1.00, 7.00), 7.50(6.00, 9.00), Z=-3.42, P=0.001], location of the occlusion(internal carotid artery/middle cerebral artery occlusion was 23/22, 11/45 cases, χ2=9.70, P=0.002), and atrial fibrillation (27 and 19 cases respectively, χ2=5.83, P=0.016) between HT group and non-HT group. Multivariate logistic regression analysis showed that ASPECTS score (OR=0.64, 95%CI 0.47-0.87), NIHSS score (OR=1.13, 95%CI 1.01-1.26), 4D CTA collateral circulation score (OR=0.40,95%CI 0.22-0.76) were independent predictors of HT in AIS patients ( P<0.05). The AUC of the nomogram based on the ASPECTS score, NIHSS score and 4D CTA collateral circulation score to predict HT of AIS patients was 0.876 (95%CI 0.807-0.945), with a sensitivity of 77.8% and specificity of 87.5%. Conclusions:Patients with low ASPECTS score, high NIHSS score and low 4D CTA collateral circulation score have a higher risk of HT after EVT. The nomogram model may predict the probability of HT of AIS patients and provide effective assistance for clinical decision-making.

【Objective】 To investigate the diagnostic value of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) specific antibodies IgM and IgG on coronavirus disease 2019 (COVID-19). 【Methods】 1) The test results of SARS-CoV-2 IgM/IgG antibodies and nucleic acid(NAT), which were tested by colloidal gold test and fluorescent quantitative PCR respectively, were collected from 145 febrile outpatients during early March, 2020, named Fever group, in which retrospective analysis and paired chi-square test were performed. 2) 612 cases of SARS-CoV-2 IgM/IgG antibodies test results, which were done on March 5, 2020, were collected. They were named COVID-19 group (Our hospital was provisionally assigned as a specialized hospital for COVID-19, and 1500 COVID-19 patients admitted to our hospital from February 12, 2020 to March 18, 2020). The SARS-CoV-2 IgM/IgG antibodies and NAT were respectively tested on the 30th and the 60th day after the date of discharge. The clinical application values of the antibodies was clarified by statistical analysis. 【Results】 1) In the fever group, the positive rate of SARS-CoV-2 IgM, IgG and IgM+ IgG antibodies were 26.21% (38/145), 54.48% (79/145) and 26.21% (38/145), respectively(P<0.01), and the positive rate of NAT was 4.14% (6/145), which was lower than that of antibody (P<0.01). One (1/145, 0.69%) positive NAT was implicated in initially negative IgM and IgG antibodies samples. 2) In the COVID-19 group, the positive rate of IgM antibody was low (5%) and IgG antibody was high (65%) during 2~14 days after infection, and stably increased during the 15~56 days [IgM 47.68%(277/581) vs IgG 94.15% (547/581) ], then both decreased after 57 days. The positive rates of IgM antibody and IgG antibody were 45.8% (280/612) and 93.1% (570/612) in 612 patients during hospitalization. 15 patients′ data after dischange were not collected as they were later transferred to Huoshenshan Hospital for treatment. The coronavirus NAT results of the rest 597 COVID-19 patients, tested on the 30th and 60th days after the date of discharge, were negative, and the positive rates of IgG antibody and IgM antibody were still ≥80% and ≥40% respectively at the second month after discharge. 【Conclusion】 IgM, IgG antibody against SARS-CoV-2 can be well detected by Colloidal gold method(Innovita), whose positive rate is higher than that of NAT. IgG antibody is produced earlier than IgM, and it keeps high positive rate and persists for a long time. The combination of colloidal gold antibody test and NAT can improve the diagnose rate of COVID-19 and the exclusion of suspected cases.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

A reliable QuEChERS-ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) analysis method was developed for the simultaneous determination of 13 steroid hormones(nrolone, androstenedione, methyltestosterone, testosterone, norethindrone, medroxyprogesterone, progesterone, diethylstilbestrol, hexan-stilbestrol, estradiol, estrotriol, cortisone, hydrocortisone) in Testis et Penis Cervi. The samples were extracted with methanol and purified by QuEChERS. Subsequently, the samples were separated by ACQUITY BEH C_(18) column and detected in the multiple reaction monitoring(MRM) mode under electrospray ionization in the positive and negative ion modes, respectively. Significant differences in the content of thirteen steroid hormones in Testis et Penis Cervi between the sika deer at different periods and the red deer were observed. The content of testosterone(10.88 μg·kg~(-1)) and hydrocortisone(12.82 μg·kg~(-1)) in Testis et Penis Cervi derived from rutting sika deer was significantly higher than the content of testosterone(1.05 μg·kg~(-1)) and hydrocortisone(0.73 μg·kg~(-1)) from antler growth stage. The content of progesterone in Testis et Penis Cervi derived from red deer was 6.07 μg·kg~(-1), significantly higher than that from sika deer. The content of progesterone in the testicle of red deer reached 27.46 μg·kg~(-1), 4.5 times greater than that in the penis of red deer. The sensitivity, accuracy, and precision of the method can meet the detection requirements, and the developed method is suitable for the measurement of hormones in animal-derived food.
Animals ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Deer ; Hormones ; Male ; Penis ; Tandem Mass Spectrometry ; Testis

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.
Bacteria ; genetics ; China ; DNA, Ribosomal ; Resins, Plant ; Thymelaeaceae

Objectives: To compare the effect of 2 different occlusion devices for treating cryptogenic stroke (CS) patients combining patent foramen ovale (PFO) and large right-to-left shunt (RLS). Methods: A total of 123 CS patients combining PFO and large RLS treated in our hospital from 2013-05 to 2016-08 were enrolled. All patients received percutaneous PFO interventional closure, based on different occlusion devices, the patients were divided into 2 groups: Cardi-O-fix PFO occluder group, n=80 and Amplatzer PFO occluder group, n=43. CS diagnosis was confirmed by 3 experienced neurologists via medical imaging examination; PFO and large RLS were diagnosed by transthoracic echocardiography and right heart contrast echocardiography. The baseline features, clinical symptoms, operation and follow-up data were reviewed to observe the efficacy of 2 occlusion devices. Results: Each group had 1 patient suffered from paroxysmal atrial fibrillation after the operation; 1 patient in Cardi-O-fix PFO occluder group had inguinal hematoma. No stroke recurrence, no death during follow-up period; the residual shunt was similar between 2 groups. Conclusions: PFO occlusion was beneficial for preventing stroke recurrence in CS patients combining PFO and large RLS. The safety and efficacy were similar in Cardi-O-fix and Amplatzer PFO occlusion devices.

The aim of this study is to establish the in vitro methods for the study of induction and inhibition on CYP450 by drugs, and to validate the analytical method and incubation system. A method for the simultaneous determination of eight metabolites of seven subtypes of CYP450 enzymes probe substrates in human liver microsomes (HLM) was established and validated. The incubation system was optimized to confirm the incubation time and protein concentration of HLM, the enzyme activity of seven subtypes of CYP450 enzymes in HLM was determined, and the inhibition effects on each CYP450s were checked by positive controls. The method for the simultaneous determination of three metabolites of subtypes of CYP450 enzymes was established and validated in human primary cultured hepatocytes (HPCH) using the incubation medium. The enzyme activity of three subtypes of CYP450 enzymes in HPCH was determined, and the total RNA was extracted from HPCH after incubation. The expression of CYP450 enzymes were measured by Taqman fluorescence probe method. The induction effects on each CYP450s were examined using the positive controls. The established methods for the determination of metabolites of probe substrates were fully validated, and the results were conformed to the requirements of bioanalytical method validation. The induction and inhibition effects on each CYP450s were checked by positive controls. The established in vitro methods for the study of drug induction and inhibition on CYP450 were simple and reliable, which could be used in the investigation of enzyme induction or inhibition properties of new drug candidates and to evaluation the metabolic interactions of concomitant medication in clinical.

OBJECTIVETo investigate the effects of gestational isoflurane exposure on postnatal memory and learning and growth-associated protein-43 (GAP-43), neuropeptide Y(NPY) expression in the hippocampus of pups.

METHODSTwelve maternal Sprague-Dawley rats at gestation d 18(E18) were randomly divided into isoflurane group (n=6) and control group (n=6). Rats in isoflurane group were exposed to 1.3 % isoflurane for 6 h. For control group, animals breathed in 30 % oxygen and air mixed gas at the same condition. Spatial learning and memory of the offspring were determined with the Morris Water Maze(MWM) after postnatal 4 weeks. The changes of GAP-43 and NPY expression in the hippocampal CA1 region of the pups were determined by immunohistochemistry.

RESULTSIn MWM training, the escape latency to platform of the pups in isoflurane group was significantly longer, and the time spent in the third quadrant and times of original platform crossing were less than those of control animals (P<0.05). The number and optical density of GAP-43 and NPY positive neurons in the hippocampus of pups decreased significantly in the isoflurane group compared with the controls (P <0.01).

CONCLUSIONIsoflurane exposure in pregnant rats significantly impairs the spatial memory and learning of their pups at a juvenile age, which may be associated with the down-regulation of GAP-43 and NPY in the hippocampus.

Animals ; Female ; GAP-43 Protein ; metabolism ; Hippocampus ; drug effects ; metabolism ; Isoflurane ; pharmacology ; Maze Learning ; drug effects ; Neuropeptide Y ; metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo construct a miR-155-based lentivirus vector to induce cyclooxygenase-2 gene silencing in nasopharyngeal carcinoma (NPC) cells by expressing anti-COX-2 shRNAmir.

METHODSmiR-155-based anti-COX-2 shRNAmir template was synthesized and inserted into pLVTHM plasmid. The recombinant pLVTHM/shRNAmir was transfected into 293FT cells for packaging the lentivirus vector. After infection with the lentivirus vector, the GFP-positive cells were screened by flow cytometry, and COX-2 mRNA level was detected by RT-PCR.

RESULTSRestriction digestion and DNA sequencing confirmed successful construction of the anti-COX-2 vector pLVTHM/shRNAmir. A subline of C666-1 cells was established after infection with the lentivirus vector, and the COX-2 expression in the cells was stably silenced.

CONCLUSIONThe shRNAmir lentivirus vector constructed may serve as an effective COX-2 inhibitor, which may facilitate future studies of gene therapy of NPC.

Cell Line, Tumor ; Cyclooxygenase 2 ; genetics ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; metabolism ; MicroRNAs ; genetics ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection