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.

Research on the convergence mechanism of the medical-nursing combined care based on synergy theory / 中华医院管理杂志

Objective:To identify the key convergence points in the medical-nursing combined care among literature, and establish a mechanism for medical-nursing combined care integration from the perspective of the synergy theory, for the purpose of promoting the integrated development of such care in China.Methods:Relevant literature on the medical-nursing combined care were retrieved from the CNKI database from September 2013 to September 2021. The search formula used was TI= "the medical-nursing care integration" AND SU=(convergence+ transformation+ coordination+ mechanism), while supplementary searches were made using " pkulaw.com database" and Baidu Scholar database. The method of literature content analysis was used to screen key points of the medical-nursing combined care, and the convergence mechanism was built based on the perspective of the synergy theory.Results:A total of 42 literatures were included in this study, 8 key convergence points of medica-nursing combined care integration were identified. Namely the 4 key horizontal convergence points of medical care, aging care, rehabilitation and nursing, the 3 key vertical convergence points of home care, institution care and community care, and the one key convergence point of institutional medical care. Based on the synergy theory and the 8 key convergence points, the " 431" convergence mechanism of medical-nursing combined care was constructed. This mechanism refered to the horizontal linkage of healthcare, nursing, rehabilitation and aging care, the vertical redirection among home care, institution care and community care modes, and the development mode focusing on institutional aging care.Conclusions:At present, the poor convergence between aging care and nursing care in China is a key roadblock hindering the integrated development of aging and nursing care. Medical-nursing combined care should be conducive to the " 431" convergence development, achieving horizontal linkage, vertical redirection, and resource sharing, for the purpose of high-quality development of China′s aging care system.

Pharmaceutical Care for A Patient with Delirium and Drowsiness Induced by Oxycodone Hydrochloride Prolonged-release Tablet During the Cancer Pain Treatment / 医药导报

Objective To discuss the pharmaceutical care protocol and methods for clinical pharmacists taking part in cancer pain management. Methods A patient developed delirium and drowsiness after using oxycodone hydrochloride prolonged-release tablet ( OXYCONTIN) and morphine hydrochloride tablet for pain titration treatment. The clinical pharmacist analyzed the reasons of delirium and drowsiness,and suggested a dose reduction of OXYCONTIN or converting OXYCONTIN to another opioid analgesic. Results The suggestion of the clinical pharmacist was partly accepted. After adjusting the treatment, the delirium and drowsiness disappeared gradually, and the pain was well controlled. Conclusion In clinical practice, especially when faced with a rare adverse drug reaction, clinical pharmacists are helpful for ensuring the safety and effectiveness in pain management, as well as improving the level of the treatment, by the implementation of individualized drug therapy.

Analysis of Risk Factors for Tramadol Induced Serotonin Syndrome / 中国药师

Objective:To investigate the clinical characteristics and causes of serotonin syndrome induced by tramadol in order to provide references for rational drug use in clinical practice. Methods:The relevant literatures published in domestic medical journals from the building of database to 2016 were retrieved in PubMed, EMbase, CNKI and WanFang database and statistically analyzed in respects of types and relevance evaluation of adverse drug reactions, the age and gender distribution of patients, the application of drugs,occurrence time of serotonin syndrome,clinical manifestations,treatment and outcome. Results:A total of 21 cases of seroto-nin syndrome induced by tramadol were collected. Totally 19 cases were caused by combined drug use, among which 12 cases were combined with selective serotonin reuptake inhibitors. The results of relevance evaluation showed 19 cases of possible relevance and 2 cases of probable relevance. Totally 10 cases of severe adverse drug reactions were reported and 11 cases of common adverse drug reac-tions were exhibited. One patient was heterozygous for CYP2D6 polymorphisms(CYP2D6?1/?4) causing decreased metabolizing a-bility to tramadol. Totally 28.6% of patients developed symptoms in 24h after the addition of new serotonergic agents or increase the dosage of serotonergic agents. In most cases,the patients' syndrome resolved with discontinuation of at least one serotonergic drug and symptomatic treatment,usually in less than one week. Conclusion:When prescribing tramadol,physicians should be aware of seroto-nin syndrome induced by drug-drug interactions and possible pharmacogenetic factors. It is important that safety monitoring should be carried out in patients during the application of drugs to reduce the harm of adverse drug reactions.

Evaluation of markers associated with primary biliary cirrhosis in a population of anti-mitochondrial antibody-M2-positive individuals / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the distribution of the main clinical symptoms and signs of primary biliary cirrhosis (PBC) in a population of individuals with positivity for anti-mitochondrial antibody-M2 (AMA-M2).</p><p><b>METHODS</b>A total of 20 970 persons who participated in routine health examinations at our hospital were tested for presence and level of antinuclear antibodies (ANAs) using an indirect immunofluorescence (IIF) assay and of AMA-M2 by western blotting. The chi-square test was used for statistical analysis.</p><p><b>RESULTS</b>Titers of ANAs more than 1:320 were detected in 1 243 of all the study participants, with 156 of those individuals having detectable AMA-M2.The overall rate ofAMA-M2 positivity was 0.74%, with a significantly higher rate among female subjects (males:0.3% (32/10 550) vs.females:1.2% (124/10 420); x2=55.85, P less than 0.05). Among the AMA-M2-positive population there were 66 cases of abnormal liver function, 58 cases of increased alkaline phosphatase, 72 cases of abnormal findings for routine blood testing, 47 cases of gallbladder disease history, 49 cases of diabetes history, 22 cases of allergy, 75 cases of abdominal discomfort, 38 cases of weakness, 3 cases of jaundice, and 11 cases of pruritus. There were significant differences between the AMA-M2-negative individuals and the AMA-M2-positive individuals.</p><p><b>CONCLUSION</b>Among the general population, individuals with substandard states of health, such as those with abnormal findings in routine blood tests and abnormal liver function, should be screened for AMA-M2. This screening will facilitate early diagnosis of PBC and timely initiation of disease management, improving the patient's life quality of life and prolonging their life.</p>

Analysis of the distribution of antinuclear antibodies in a healthy population / 中华微生物学和免疫学杂志

Objective To study the distribution of antinuclear antibodies ( ANAs) in a healthy population and the significance of using ANAs screening test in medical examination .Methods The ANAs were measured by indirect immunofluorescence assay ( IIF) .The Western blot assay was used to detect fif-teen specific antibodies against auto-antigens .Results 3519 out of all 25 110 subjects showed ANAs titers>1∶100 , and among them male and female subjects were respectively accounted for 1143 and 2376 .1489 out of all subjects had ANAs titers >1∶320 , and among them male and female subjects were respectively accounted for 406 and 1083 .The positive rates of ANAs at different titers showed significant differences be -tween male and female subjects .Among subjects with ANAs titers >1∶320 , the number of male subjects showed a steady increase with the age , while the percentage of female subjects reached to two peaks during the periods of puberty and menopause .The fifteen specific antibodies were detected in 659 out of 1489 sub-jects with ANAs titers>1∶320 and anti-Ro-52 (14.2%) accounted for the majority , followed by anti-M2 (12.7%) and anti-SSA (9.6%).Conclusion ANAs can be detected among healthy population of all ages, but their distribution varied with gender and age .ANAs screening test is necessary for medical exami-nation of healthy population , especially for female during period of puberty or menopause .The population with positive ANAs should be followed-up closely and educated for the prevention of autoimmune diseases .

Effects of Capsaicin on Rat Cytochrome P450 Isoforms by Cocktail Probe Drug Method / 中国药师

Objective:To investigate the in vitro effect of capsaicin on four major rat cytochrome P450 ( CYP) enzymes using a cocktail probe drug method. Methods:The in vitro incubation was divided into capsaicin group and the control group. Rat liver micro-somes, probe drugs, capsaicin at various concentration ( buffer solution in the control group) and cofactors were cultured altogether for 20 min. After the culture, the concentration of metabolites was determined by HPLC to assess the activities of enzymes. IC50 value of capsaicin on every isoform was calculated using Graphpad prism 5. 0. Capsaicin and hepatic microsomess were pre-incubated respec-tively for 0, 5, 10, 15, 20 and 30 min, and then the relative activity of the four isoforms at different time was calculated. Results:The activity of the rat liver microsomes enzyme CYP450 isoforms (CYP1A2, CYP2C11, CYP2E1 and CYP3A2) was all inhibited by capsaicin in vitro with IC50 value of 36. 21, 17. 19, 51. 64 and 18. 86 μmol·L-1 , respectively. Pre-incubation could not increase cap-saicin inhibitory activity against the four CYP enzymes. Conclusion:Capsaicin shows inhibition on CYP1A2, CYP2C11, CYP2E1 and CYP3A2 in rat liver microsomes in vitro without pre-incubation time-dependent property.

A simple and sensitive liquid chromatographic technique for the determination of cefotetan disodium in human plasma and its application in a pharmacokinetic study / 华中科技大学学报（医学）（英德文版）

A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525-300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.

A simple and sensitive liquid chromatographic technique for the determination of cefotetan disodium in human plasma and its application in a pharmacokinetic study / 华中科技大学学报（医学）（英德文版）

A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525-300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.

Automatic segmentation of the sequential images of neural stem cell based on geometric active contour / 生物医学工程学杂志

A rapid and robust segmentation system is the base of the research on the change process of neural stem cells. In order to improve this system, against the segmentation of the multiple connected and blurred border cells, we present an improved geometric active contour algorithm based on the level set method and the curve evolution theory. This method can solve the topological change by itself and obtain the more real edges of the cells. This method has been adopted in the segmentation of the sequence of neural stem cell. The results prove the validity and veracity.