Incidence of adverse drug reactions in COVID-19 hospitalised patients through the minimum basic data set / Incidencia de reacciones adversas a medicamentos en pacientes hospitalizados por COVID-19 a través del conjunto mínimo básico de datos

Background: At the beginning of the COVID-19 pandemic many drugs were used with an uncertain benefit/risk profile that needed to be evaluated. The goal of this study was to analyse the incidence of adverse drug reactions (ADRs) and describe the drugs used in COVID-19 hospitalised patients at the beginning of the COVID-19 pandemic through the minimum basic data set (MBDS). Methods: Retrospective observational study that included hospitalised patients with COVID-19 at our centre between March and May 2020 who had ADRs coded in discharge/death medical reports according to the International Classification of Diseases (ICD-10). Those patients with ADRs ascribed to COVID therapy were selected and the causal relationship was evaluated using the Naranjo algorithm. Descriptive statistical analysis was used. Results: We identified 141 ADRs in 110 cases of hospitalisation due to COVID-19 that entailed an incidence of 9.66% (141/1459), CI95% 8.25-11.29. From the ADRs analysed, 60.3% (85/141) were ascribed to COVID therapy. Lopinavir/ritonavir represented 38.8% (33/85) of ADRs, glucocorticoids 23.5% (20/85) and hydroxychloroquine 9.4% (8/85). Out of the ADRs, 31.8% (27/85) were gastrointestinal disorders (probable lopinavir/ritonavir), 27.0% (23/85) blood glucose disorders (probable glucocorticoid) and 17.6% (15/85) hypertransaminasaemia (probable azithromycin, possible lopinavir/ritonavir, possible hydroxychloroquine, possible interferon). Regarding intensity, 64.7% (55/85) were mild cases, 29.4% (25/85) moderate and 5.9% (5/85) severe. The percentage of ADRs that did not require intervention were 24.7% (21/85), 32.9% (28/85) required pharmacological treatment, 40.0% (34/85) suspension of the drug, 1.2% (1/85) close monitoring and 1.2% (1/85) dose reduction. Conclusions: The incidence of ADR in COVID population that required admission at the beginning of the pandemic seems to be higher than in the general population. The MBDS proves to be a useful tool to trace ADRs. (AU)

Introducción: La llegada de la pandemia de COVID-19 supuso la utilización de muchos fármacos con un perfil de riesgo/beneficio incierto que debe ser evaluado. El objetivo de este estudio fue analizar la incidencia de reacciones adversas a medicamentos (RAM) y describir los medicamentos utilizados en pacientes hospitalizados por COVID-19 al comienzo de la pandemia a través del conjunto mínimo básico de datos (CMBD). Materiales y métodos: Estudio observacional retrospectivo que incluyó pacientes hospitalizados por COVID-19 en nuestro centro entre marzo y mayo de 2020 que presentaban RAM codificadas en los informes médicos de alta/exitus según la Clasificación Internacional de Enfermedades (CIE-10). Se seleccionaron los pacientes con RAM atribuidas a la terapia COVID-19 y se evaluó la relación causal mediante el algoritmo de Naranjo. Se realizó un análisis estadístico descriptivo. Resultados: Identificamos 141 RAM en 110 casos de hospitalización por COVID-19 lo que supone una incidencia del 9,66% (141/1459), IC95% 8,25-11,29. De las RAM analizadas el 60,3% (85/141) se atribuyeron a la terapia COVID. Lopinavir/ritonavir representó el 38,8% (33/85) de las RAM, los glucocorticoides el 23,5% (20/85) y la hidroxicloroquina el 9,4% (8/85). De todas las RAM, el 31,8% (27/85) fueron trastornos gastrointestinales (probable lopinavir /ritonavir), el 27,0% (23/85) trastornos de la glucemia (probable glucocorticoide) y el 17,6% (15/85) hipertransaminasemia (probable azitromicina, posible lopinavir /ritonavir, posible hidroxicloroquina, posible interferón). En cuanto a la intensidad, el 64,7% (55/85) de las RAM fueron casos leves, el 29,4% (25/85) moderados y el 5,9% (5/85) graves. El porcentaje de RAM que no requirió intervención fue 24,7% (21/85), 32,9% (28/85) requirió tratamiento farmacológico, 40,0% (34/85) suspensión del fármaco, 1,2% (1/85) seguimiento estrecho y 1,2% (1/85) reducción de dosis... (AU)

Technological innovation and clinical application of direct percutaneous computed tomography-guided enterostomy vs other enterostomy techniques.

BACKGROUND: To investigate the technological innovation, safety, operational advantages, and clinical application value of direct percutaneous computed tomography (CT)-guided enterostomy. METHODS: This retrospective study included patients who underwent direct percutaneous CT-guided enterostomy (n = 52), percutaneous endoscopic gastrojejunostomy (PEG-J, n = 39), or laparoscopic jejunostomy (n = 68) at Fujian Provincial Hospital between October 2019 and July 2021. The study indices included stoma surgery success rate, operation time, complication rate, and postoperative pain score. We concurrently analyzed the technological innovation of direct percutaneous CT-guided enterostomy and the changes in body mass index (BMI), serum albumin, prealbumin, and C-reactive protein (CRP) levels and patient-generated subjective global assessment (PG-SGA) scores after patients received 2 months of nutritional support. RESULTS: Direct percutaneous CT-guided enterostomy had a high success rate (100%) and low postoperative complication rate (5.77%). Compared to laparoscopic jejunostomy, direct percutaneous CT-guided enterostomy had a shorter operation time (36.92 ± 10.60) minutes, lower postoperative pain score (4.06 ± 2.02), lower anesthesia risk, and lower operative cost. The anesthetic risk for direct percutaneous CT-guided enterostomy is lower than that for PEG-J and has wider applications. After 2 months of postoperative nutritional support, patients had increased BMI, serum albumin level, and serum prealbumin level and decreased PG-SGA scores and CRP level with statistically significant differences compared to the preoperative state ( p < 0.05). CONCLUSION: Direct percutaneous CT-guided enterostomy is an important method of establishing an enteral nutrition therapy pathway, especially when endoscopic jejunostomy is not possible. It has a high safety profile and few complications, has unique advantages, and deserves further promotion of its application in clinical practice.

Development and validation of an UHPLC-Orbitrap-HRMS method for rapid determination of endogenous L-carnitine in patients on hemodialysis/peritoneal dialysis and its application to promote rational drug use.

Background: L-carnitine is an endogenous vitamin-like amino acid derivate which plays an essential role in energy metabolism and can be easily lost via dialysis. Deficiency of L-carnitine has great effects on many aspects of bodily functions. To determine the deficiency degree and adjust the supplementation dose, a rapid, sensitive, and specific method for the detection of endogenous L-carnitine in the plasma of dialysis patients using ultra-high performance liquid chromatography-Orbitrap high resolution mass spectrometry (UHPLC-Orbitrap-HRMS) was developed and validated. Methods: The plasma samples were processed by protein precipitation and centrifugation before analysis using UHPLC-Orbitrap-HRMS. Sample separation was achieved with a hydrophilic interaction liquid chromatography (HILIC) column, using an isocratic elution with a runtime of 5 min. The separated analytes were detected by positive ionization mode in full scan mode and targeted-single ion monitoring (t-SIM) mode. Mildronate was used as the internal standard (IS). Results: All the plasma could be detected in the range of 6.169 to 197.394 µM, with adequate accuracy, precision, and recovery. The method was validated in fortified validation with relative standard deviations (RSD) 5.15-8.74%. This method was applied to the analysis of 105 dialysis patients and 39 healthy participants, the results revealed that peritoneal dialysis patients without L-carnitine supplementation should pay more attention to L-carnitine monitoring, meanwhile, all the hemodialysis patients were advised to be routinely given a full dose of L-carnitine, no matter whether they had taken L-carnitine or not. Conclusions: This study developed a simple and rapid UHPLC-Orbitrap-HRMS method for detection of endogenous L-carnitine in dialysis patients, which could be useful to promote rational drug use.

Physical Activity and Liver Cancer Risk: A Systematic Review and Meta-analyses.

OBJECTIVE: Liver cancer is the second most common cause of death from cancer. Physical activity (PA) was found to be associated with lower risks of several types of cancer. However, the association between PA and the risk of liver cancer is still inconclusive. This systematic review and meta-analysis was aiming to summarize the association between PA and liver cancer risk. METHODS: Literatures related were identified by searching PubMed, EMBASE, and Chinese Biomedical literature database from 1965 to 2017 without language limitation. Meta-analyses were performed using random effect model. RESULTS: A total of 5 cohort studies involving 2 513 975 subjects were identified. The pooled relative risk of leisure-time PA with liver cancer risk was 0.92 [95% confidence interval (CI), 0.84-1.01]. There is no significant association between leisure-time PA and liver cancer risk. However, leisure-time PA significantly reduced liver cancer risk in never smokers. The pooled hazard ratio of daily total PA with liver cancer risk was 0.75 (95% CI, 0.66-0.86). CONCLUSIONS: Daily total PA significantly reduces liver cancer risk, whereas leisure-time PA significantly reduces liver cancer risk only in never smokers.

Role of ERK1/2/CREB/BDNF signaling pathway in dexmedetomidine-induced inhibition of propofol-caused apoptosis in isolated hippocampal neurons of fetal rats / 中华麻醉学杂志

Objective:To evaluate the role of extracellular signal-regulated kinase 1/2 (ERK1/2)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in dexmedetomidine-induced inhibition of propofol-caused apoptosis in isolated hippocampal neurons of fetal rats.Methods:Pregnant Sprague-Dawley rats at 16 days of gestation were sacrificed, and the fetal rats were taken out, and hippocampal neurons of fetal rats were obtained and primarily cultured in vitro for 7 days.The neurons were divided into 9 groups ( n=12 each) using a random number table method: control group (group C), fat emulsion group (group I), dimethyl sulfoxide (DMSO) group, dexmedetomidine group (group D), propofol group (group P), propofol plus dexmedetomidine group (group PD), PD98059 plus propofol plus dexmedetomidine group (group PDP), MH89 plus propofol plus dexmedetomidine group (group HDP), and KG501 plus propofol plus dexmedetomidine group (group KDP). Group C received no treatment.In group I, 20% fat emulsion was added, and the neurons were incubated for 30 min, and 0.25% DMSO was added in group DMSO, and the neurons were incubated for 30 min.Dexmedetomidine at a final concentration of 10 μmol/L was added, and the neurons were incubated for 30 min in group D. Propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h in group P. In group PD, dexmedetomidine at a final concentration of 10 μmol/L was added, the neurons were incubated for 30 min, propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h. In PDP, HDP and KDP groups, 25 μmol PD98059 (p-ERK1/2 inhibitor), 10 μmol H89 (p-CREB inhibitor) and 25 μmol KG501 (CREB inhibitor) were added, respectively, the neurons were incubated for 30 min, dexmedetomidine at a final concentration of 10 μmol/L was added, the neurons were incubated for 30 min, and propofol at a final concentration of 100 μmol/L was added, and the neurons were incubated for 3 h. The cell ultrastructure was observed with the transmission electron microscope, the apoptosis in neurons was detected by flow cytometry, the expression of ERK1/2, CREB and BDNF mRNA was detected by quantitative real-time polymerase chain reaction, and the expression of p-ERK1/2, CREB, p-CREB, BDNF and cleaved caspase-3 was detected by Western blot. Results:Compared with group C, the apoptosis rate was significantly increased, the expression of p-ERK1/2 and p-CREB was down-regulated, and the expression of cleaved caspase-3 was up-regulated in P, PD, PDP, HDP and KDP groups, and the expression of BDNF was significantly down-regulated in P, PDP, HDP and KDP groups ( P<0.05). Compared with group P, the apoptosis rate was significantly decreased, the expression of p-ERK1/2, p-CREB and BDNF was up-regulated, and the expression of cleaved caspase-3 was down-regulated in group PD ( P<0.05). Compared with group PD, the apoptosis rate was significantly increased, the expression of p-ERK1/2, p-CREB and BDNF was down-regulated, and the expression of cleaved caspase-3 was up-regulated in PDP, HDP and KDP groups ( P<0.05). Conclusion:The ERK1/2/CREB/BDNF signaling pathway is involved in dexmedetomidine-induced inhibition of propofol-caused apoptosis in isolated hippocampal neurons of fetal rats.

Effect of painting intervention based on Mandala-self theory on mood and physiological state in patients in preoperative waiting room / 中南大学学报(医学版)

OBJECTIVES@#The waiting room for surgery is an area set up to improve the surgical turnover rate, but the waiting time for surgery is uncertain. Patients are prone to negative emotions that affect their physiological state during waiting time. This study aims to explore the effect of Mandala painting intervention based on Mandala-self theory on the emotion and physiological state of patients waiting before operation.@*METHODS@#The patients in the control group (@*RESULTS@#Diastolic pressure, heart rate, and happiness and excitement showed no statistical significance in the time effect, intervention effect, and interaction between the 2 factors (all @*CONCLUSIONS@#The application of Mandala painting in the operation waiting room is feasible and can effectively regulate the patients' negative mood and systolic pressure, as well as shorten the waiting time of perception.

Clinical Characteristics and Prognostic Analysis of Patients With Signet Ring Cell Gastric Carcinoma.

We do not know the clinical and prognostic factors that influence the survival of patients with gastric signet ring cell carcinoma (SRC). Therefore, a retrospective review was undertaken of 219 patients with SRC who had undergone gastrectomy between January 2009 and December 2012 in our hospital. Patient age, sex, TNM stage, vessel carcinoma embolus, perineural invasion, tumor site and operation type, postoperative chemotherapy, and five-year overall survival were recorded and evaluated. In our study, 93 cases (42.5%) were signet ring cell carcinoma only, and 126 cases (57.5%) were signet ring cell carcinoma coexisting with other components (such as adenocarcinoma or mucus adenocarcinoma). Eighty-three patients were female, 136 were male, 46 occurred at the gastroesophageal junction (21.0%), 63 at the fundus/body (28.8%), 80 were antrum/pylorus (36.5%), and 30 were whole stomach (13.7%). The prognosis of gastric antrum/ pylorus cancer was the best (P < 0.05). There were 133 patients (60.7%) with stage III, and the single factor analysis showed that the earlier the stage, the better the prognosis. The overall five-year survival rate was 30.1% in all patients. One-hundred and 41 patients (64.4%) received D2 radical surgery, 64 (29.2%) received D1 radical operation, and 14 (6.4%) received palliative resection, and the patients who received D2 had the best overall survival (P < 0.05). The survival time of the paclitaxel-based regimen in postoperative adjuvant chemotherapy tended to be prolonged. There was no statistical difference in overall survival between the percentage of signet-ring cells and sex. In summary, age, tumor stage, and surgical resection combined with D2 lymphadenectomy were independent prognostic factors for SRC. Adjuvant chemotherapy with a paclitaxel-based regimen may improve the survival of patients with SRC.

COVIEdb: A database for potential immune epitopes of coronaviruses

2019 novel coronavirus (2019-nCoV) has caused large-scale pandemic COVID-19 all over the world. Its essential to find out which parts of the 2019-nCoV sequence are recognized by human immune system for vaccine development. And for the prevention of the potential outbreak of similar coronaviruses in the future, vaccines against immunogenic epitopes shared by different human coronaviruses are essential. Here we predict all the potential B/T-cell epitopes for SARS-CoV, MERS-CoV, 2019-nCoV and RaTG13-CoV based on the protein sequences. We found YFKYWDQTY in ORF1ab protein, VYDPLQPEL and TVYDPLQPEL in spike (S) protein might be pan-coronavirus targets for vaccine development. All the predicted results are stored in a database COVIEdb (http://biopharm.zju.edu.cn/coviedb/).

Sclerotherapy and Topical Nasal Propranolol: An Effective and Safe Therapy for HHT-Epistaxis.

OBJECTIVES: Epistaxis is the most frequent clinical manifestation of hereditary hemorrhagic telangiectasia (HHT). Several topical, systemic, and surgical treatments have been tried, but none have been completely effective. The aim of the present study is to evaluate whether a combined treatment sclerotherapy and topical therapy with propranolol 0.5% nasal formulation would reduce the epistaxis due to HHT and improve patient's quality of life. METHODS: An observational cross-sectional study was carried out. The primary outcome measure was frequency and severity of epistaxis as measured by the epistaxis severity score (ESS) at baseline (4 weeks before therapy) and at least 4 weeks after the treatment was implemented. Quality of life was analyzed using EuroQol-5D (EQ-5D) scale and visual analogue (VAS) scale before and after treatment. RESULTS: A total of 38 consecutive patients subjected to the combined treatment were evaluated (mean age: 57.2 years, standard deviation [SD] = 13.9; 60.5% women). The mean time of treatment was 37.1 weeks (SD = 14.9). Combined therapy significantly reduces frequency and severity of epistaxis, with an ESS improvement of 5 points from 6.9 ± 2.6 to 1.9 ± 1.3 (P < 0.05); however, the EQ-5D scale increased from 0.66 ± 0.27 to 0.93 ± 0.12 (P < 0.05). The difference in VAS means showed an increase from 44.6 ± 28.3 to 82.5 ± 12.5 (P < 0.05). The increases in quality of life are in line with the drop in ESS. CONCLUSION: The study demonstrated that combined therapy (sclerotherapy and topical nasal propranolol) significantly reduced the epistaxis due to HHT and increased patients' quality of life. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:2216-2223, 2019.

Abnormal resting-state functional connectivity in posterior cingulate cortex of Parkinson's disease with mild cognitive impairment and dementia.

OBJECTIVE: To investigate changes in the functional connectivity (FC) pattern in the posterior cingulate cortex (PCC) of Parkinson's disease (PD) patients with mild cognitive impairment and dementia by employing resting-state functional magnetic resonance imaging (RS-fMRI). METHODS: Twenty-seven PD patients with different cognitive status and 9 healthy control subjects (control group) were enrolled for RS-fMRI. The RS-fMRI data were analyzed with DPARSF and REST software. Regions with changed functional connectivity were determined by the seed-based voxelwise method and compared between groups. Correlation between the intensity of FC and the MoCA scores of PD group was analyzed. RESULTS: Parametric maps showed statistical increases in PCC functional connectivity in PD-MCI patients and decreases in PCC connectivity in PDD patients. The latter group of patients also showed evidence for increased connectivity between prefrontal cortices and posterior cerebellum. A significant positive correlation was found between the MoCA scores and the strength of PCC connectivity in the angular gyrus and posterior cerebellum and a negative correlation between MoCA scores and PCC connectivity in all other brain regions. CONCLUSION: When patients transition from PD-NCI to PD-MCI, there appears to be an increase in functional connectivity in the PCC, suggesting an expansion of the cortical network. Another new network (a compensatory prefrontal cortical-cerebellar loop) later develops during the transition from PD-MCI to PDD.

Synthesis and biological evaluation of estrone 3-O-ether derivatives containing the piperazine moiety.

A series of new estrone derivatives were designed and synthesized, and their structures were confirmed by spectroscopic methods. All new estrone derivatives were investigated for their in vitro cytotoxic efficacies against a panel of three human prostate cancer cell lines (PC-3, LNCaP, and DU145). The derivatives 6, 7, 10, 15, 16, 20, 21, 22, 24 and 26 showed important cytotoxic actions against individual carcinoma cell line collections. Moreover, antagonistic activities of compounds (7, 15, 16 and 21) towards a1-ARs (α1A, α1B, and α1D) were further evaluated using dual-luciferase reporter assays, and the compounds 16 and 21 exhibited better a1-ARs subtype selectivity. The structure-activity relationship (SAR) suggested that the substitute's type and position on the phenyl group leads to the interesting variations within pharmacological effects of resultant molecular systems.

TSNAdb: A Database for Tumor-specific Neoantigens from Immunogenomics Data Analysis / 基因组蛋白质组与生物信息学报·英文版

Tumor-specific neoantigens have attracted much attention since they can be used as biomarkers to predict therapeutic effects of immune checkpoint blockade therapy and as potential targets for cancer immunotherapy. In this study, we developed a comprehensive tumor-specific neoantigen database (TSNAdb v1.0), based on pan-cancer immunogenomic analyses of somatic mutation data and human leukocyte antigen (HLA) allele information for 16 tumor types with 7748 tumor samples from The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA). We predicted binding affinities between mutant/wild-type peptides and HLA class I molecules by NetMHCpan v2.8/v4.0, and presented detailed information of 3,707,562/1,146,961 potential neoantigens generated by somatic mutations of all tumor samples. Moreover, we employed recurrent mutations in combination with highly frequent HLA alleles to predict potential shared neoantigens across tumor patients, which would facilitate the discovery of putative targets for neoantigen-based cancer immunotherapy. TSNAdb is freely available at http://biopharm.zju.edu.cn/tsnadb.

Mechanism of the occurrence of sarcopenia in the elderly / 生理学报

The decline in skeletal muscle mass and function with age is referred as sarcopenia. It is characterized by the muscle fiber's quality, strength, muscle endurance and metabolic ability decreasing as well as the fat and connective tissue growing. Previous studies have shown that sarcopenia in itself features decreased number and cross-sectional area of muscle fibers and the net degradation of protein, which results from the joint effects of multiple factors such as the exacerbation of inflammation, oxidative stress injury, mitochondrial dysfunction, abnormal autophagy and dysregulation of muscle quality regulatory factors. In this review, we systematically displayed the molecular mechanism of sarcopenia, which will be helpful to deepen our understanding of sarcopenia and provide potential targets for the prevention and treatment of sarcopenia.

Fat deposition in skeletal muscle and its regulation / 生理学报

Under normal condition, there are a few lipid droplets in skeletal muscle. But in skeletal muscle acute injury, muscular dystrophy, muscle atrophy, obesity, diabetes and other pathological conditions, the fat deposition in skeletal muscle increases, which implicate that the fat deposition may play an important role in the pathogenesis of these diseases. However, the mechanisms of development and regulation of fat deposition in skeletal muscle are not clear. Clarifying the key signaling pathways and regulatory factors that affect fat deposition in skeletal muscle, and exploring new ways to improve the fat deposition in skeletal muscle will not only help to deepen our understanding of the pathogenesis of these diseases, but also provide new ideas for the treatment of these diseases. This paper reviews the research progresses and main mechanisms of fat deposition in skeletal muscle.

Analysis of online Mendelian inheritance in man / 中国生化药物杂志

Objective To analyze the data from Online Mendelian Inheritance in Man (OMIM) to understand more about it, and provide reference to researchers using this database.Methods 19414 mutations which have definite relevant phenotypes from OMIM were obtained, then these mutations with three databases (1000 Genome Project,GO-ESP,ExAC) which record the mutation frequency in different population were compared.Results Most of the phenotype-related mutations from OMIM are rare mutations whose mutation frequency is less than 1%:18866 in 1000 Genome Project, 18981 in GO-ESP, 18979 in ExAC.The number of mutation whose frequency is more than 1% is 548433435 in 1000 Genome Project, GO-ESP, ExAC, respectively.And there are 320 mutations whose frequency is more than 1% in all databases.In all phenotypes, there are 127 polymorphism phenotypes, 584 susceptibility phenotypes, while in 320 ( 1.6%) phenotypes with common mutations, there are 62 polymorphism phenotypes, 88 susceptibility phenotypes and occupies 48.8%, 15.1%, respectively.Conclusion Approximately 97.5% mutations in OMIM are rare mutations.Polymorphism and susceptibility enrich in common mutations, especially in the mutation whose frequency is more than 10%.

Bibliometric analysis of antibody-drug conjugates / 中国生化药物杂志

Objective To retrieve and analyze domestic and international literatures about antibody-drug conjugates, and understand the recent progress and current situation.Methods PubMed, Web of Science and CNKI were searched to collect all the literatures connected with ADCs from the beginning to January, 2016.Endnote X7 was used to sort out and summarize.The type of literature, published year, first author, research institution, published journal, cited frequency, research contents and patent situation were analyzed with bibliometric methods.Results A total of 645 literatures were included, among which 495 were foreign articles and 150 were Chinese articles.The literatures greatly increased after the 21st century.The top one nation and journal which published the most articles were America and Clinical Cancer Research, respectively.Krop IE and Younes A published the most articles.Among them, the most frequently cited paper was cited up to 686 times.Selection of the targets, site-specific drug conjugation to antibodies and cytotoxic agents were frequently involved.Conclusion ADCs, which have made breakthrough progress, are the focus in the field of cancer research.However, there is still room for improvement, and we still need further exploration.

Analysis of somatic mutations in membrane proteins of tumor cells / 中国生化药物杂志

Objective To screen specific mutations on extracellular regions of membrane proteins ( extracellular membrane protein mutations ) in tumor cells and provide the reference information for target searching in cancer precision medicine .Methods Somatic mutations on extracellular regions of membrane proteins of 7042 tumor samples were collected to screen all specific extracellular membrane protein mutations, and the overall distribution of these mutations were obtained by statistical analysis.Genes, gene site and cancer types occured high frequency of extracellular membrane protein mutations were identified.Results 97193 specific extracellular membrane protein mutations were obtained from 4938362 somatic mutations in 7042 tumor samples (30 cancer types), the statistical analysis showed that 4347 genes and 65532 sites were involved in these specific mutations.The study further analyzed five genes (MUC16、LRP1B、CSMD3、RYR2、USH2A), one site (17:37868208) and six cancer types (including colorectal cancer, melanoma, uterine cancer, brain lower grade glioma, lung adenocarcinoma and stomach adenocarcinoma) which occured high frequency of extracellular membrane protein mutations.Conclusion An information library of specific mutations on extracellular regions of membrane proteins was established and the distribution of these specific mutations was obtained which can provide reference information for target detection in targeted cancer therapy and immunological therapy.

[Inner- and inter-species differences of mercury concentration in common fishes from the Yellow Sea].

Mercury concentration in marine fishes and its influencing factors are the key problems in the study of mercury biomagnification in marine ecosystems. In order to understand the inner- and inter-species differences of mercury concentration in fishes from the Yellow Sea, a total of 164 marine wild fishes covering nine different species were collected from the area from August to October, 2012. Mercury (total mercury) concentration in fish muscle tissue was measured by a direct mercury analyzer. Body length and wet weight of each sample were also determined. Moreover, feeding habit and trophic level of different species were examined. Hg concentrations (dry weight) in the muscle tissues of the 164 individuals ranged from 0.025 micro x g(-1) to 0.526 microg x g(-1), with an average of (0.124 +/- 0.096) microg x g(-1). By an inner-species analysis, log10 Hg concentration was significantly correlated to their body length and wet weight. Predator fishes with trophic level > 2.8 were more readily to be contaminated by Hg than the filter feeder with trophic level < 2.8. Furthermore, species with higher increasing rate of weight had lower Hg concentration in the muscle due to growth dilution. The results suggest that length and weight are the main factors affecting the inner- species difference of mercury concentration in common fishes from the Yellow Sea, while dietary preference, trophic level and increasing rate of weight are the main factors affecting the inter-species difference from the Yellow Sea.

Analgesic, anti-inflammatory, and antipyretic activities of the ethanol extract from Desmodium caudatum.

CONTEXT: In folk medicine in China, Desmodium caudatum (Thunb.) DC (Leguminosae) has been used to treat febrile diseases, rheumatic arthritis, and bacillary dysentery; nevertheless, there have been no reports on the analgesic, antipyretic, and anti-inflammatory effects of this plant in animals. OBJECTIVE: To investigate the analgesic, anti-inflammatory, and antipyretic activities of D. caudatum extract (DCE) in animals. MATERIALS AND METHODS: The analgesic effect of DCE was measured in mice using the acetic acid-induced writhing test and the hot-plate test. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model and the dimethylbenzene-induced mouse inflammation model. The antipyretic effect was estimated using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of DCE was studied. RESULTS: DCE significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time in mice in the hot-plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. Furthermore, no death was observed when mice were orally administered DCE up to 40 g/kg. DISCUSSION AND CONCLUSION: DCE possesses evident analgesic, anti-inflammatory, and antipyretic activities, and has a favorable safety, which supports the use of D. caudatum as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.

Essential oil from rhizomes of Ligusticum chuanxiong induces apoptosis in hypertrophic scar fibroblasts.

CONTEXT: Hypertrophic scarring following surgical procedures, trauma and especially burns can lead to severe functional and cosmetic impairment, causing a decrease in the quality of life. Although a wide choice of treatments is offered, few therapeutic methods are universally accepted because of their side effects. OBJECTIVE: The effects of the essential oil (EO) extracted from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) in human hypertrophic scar fibroblasts (HSFs) are investigated for the first time. MATERIALS AND METHODS: Chemical composition of hydrodistilled EO obtained from rhizomes of Ligusticum chuanxiong was analyzed by gas chromatography-mass spectrometry (GC-MS). The effects of EO on cell viability, apoptosis rate, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH), reactive oxygen species (ROS) and caspase-3 in HSFs were investigated. RESULTS: The experimental results showed that EO significantly inhibited cell viability, elicited morphological changes and induced apoptosis in HSFs. EO also evidently increased the loss of MMP, the levels of LDH release and cellular ROS production, and the activity of caspase-3. DISCUSSION AND CONCLUSION: EO-induced apoptosis was at least partially carried out via destruction of the intracellular antioxidant system and elicitation of excessive ROS accumulation in HSFs, which impaired mitochondrial membranes and elicited caspase-3 activation. EO could be an effective cure for human hypertrophic scar.