摘要
Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3%,and that of non-infected group was 23.1%,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2%(95%CI:-2.3%-22.8%).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P>0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P>0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.
摘要
The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.
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Objective To explore the common parameters of cervical spine bone age of Uighur adolescents in Urumqi,derive the regression equation of cervical spine bone age of Uighur adolescents in Urumqi,and evaluate the significance of its application in prediction of biological age.Methods Part I:A total of 300 Uygur adolescent patients(150 males and 150 females)aged 7~16 years who were admitted to the orthodontic Department of Urumqi Stomatology Hospital from January 2017 to October 2020 were selected.Fixed point measurements were performed on the third and fourth cervical vertebrae(AH3,PH3,AP3,H3,AH4,PH4,AP4,H4).The corresponding ratios representing the morphological changes of cervical cone were obtained(AH3/AP3,AH3/H3,H3/AP3,H3/PH3,PH3/AP3,AH4/AP4,AH4/cervical bone age of Uygur teenagers in Urumqi city.Part II:A total of 192 Uygur adolescent patients(91 males and 101 females)aged 7~16 years old who were admitted to the orthodontic Department of Urumqi Stomatology Hospital from November 2020 to December 2022 were selected.The measured values of the third and fourth cervical vertebrae were substituted into the regression equation of adolescent cervical bone age obtained in part I to analyze the correlation between biological age and cervical bone age.Results Part I:The estimated age was obtained through the regression equation of cervical spine bone age of female and male adolescents proposed by Mito.The matching analysis results with biological age showed that the estimated age of cervical spine bone age of female and male adolescents was different from biological age,and the difference was statistically significant.Taking the actual age of the samples as the dependent variable and the measured ratios of the third and fourth cones as the independent variables,the calculation equation of cervical bone age of Uygur teenagers in Urumqi city was derived by using multiple stepwise regression analysis. Male:CVBA = 2.551-2.151×AH3/AP3 + 8.884×H4/AP4 + 3.198×H3/PH3,(R = 0.804); Female:CVBA = 3.607 + 2.743×H3/AP3 + 9.967×H4/AP4-3.135×H4/PH4,(R = 0.792). Part Ⅱ:By Spearman correlation analysis,male cervical spine bone age was highly correlated with biological age(r = 0.821,P<0.05).There was a high correlation between cervical spine bone age and biological age(r = 0.830,P<0.05).Conclusion The equation of cervical vertebra bone age of Uygur adolescents in Urumqi derived from lateral radiographs is helpful to predict individual growth and development potential in clinical work,and to guide clinical diagnosis and treatment.It can provide some reference for inferring the biological age of Uygur Adolescents in Forensic Science;However,it can not accurately reflect the biological age,and the accuracy still needs further improvement.
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Dizziness and vertigo are common clinical symptoms,which requires clinicians to timely identify dizziness and vertigo due to acute stroke,so as not to delay diagnosis and treatment.In previous studies,such stroke was usually attributed to subtentorial vascular lesions such as brainstem and cerebellum.With increasing reports of vestibular symptoms caused by supratentorial stroke,researchers have found that vestibular symptoms caused by stroke are not unique to supratentorial lesions.This paper expounds the morbidity,influencing factors,pathogenesis,clinical manifestations,examination methods,treatment and prognosis of vestibular symptoms related to supratentorial stroke,in order to improve the understanding of clinicians to this disease.
摘要
To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.
Subject(s)
Humans , Rhododendron/chemistry , Neuroblastoma , Oxidative Stress , Magnetic Resonance Spectroscopy , Stereoisomerism , Molecular Structure摘要
Three new cucurbitane-type triterpenoid glycosides were separated from the ethyl acetate extract of Citrullus colocynthis by a variety of chromatographic techniques. According to the data of NMR, HR-ESI-MS, and/or comparison with the reported data, the three novel cucurbitane-type triterpenoid glycosides were identified as colocynthenin E(1), colocynthenin G(2), and colocynthenin H(3). The cell inflammation model was established with RAW264.7 macrophages exposed to lipopolysaccharide and then used to determine the anti-inflammatory activities of the three compounds. Compounds 2 and 3 showed mild anti-inflammatory activities with the IC_(50) of 48.21 and 40.11 μmol·L~(-1), respectively, compared with that(IC_(50)=7.57 μmol·L~(-1)) of the positive control dexamethasone.
Subject(s)
Citrullus colocynthis/chemistry , Triterpenes/chemistry , Glycosides/chemistry , Plant Extracts/chemistry , Anti-Inflammatory Agents/pharmacology摘要
Objective:To explore the application value of four-dimensional automatic left ventricular quantitation(4D Auto LVQ) technology, in evaluating the myocardial mechanics in patients with different risk stratifications of hypertrophic cardiomyopathy(HCM).Methods:A total of 88 HCM patients and 20 healthy volunteers were selected from February 2020 to February 2022 in the First Affiliated Hospital of Zhengzhou University. According to the HCM Risk-SCD score, HCM patients were divided into 3 groups: low-risk group( n=49), intermediate-risk group( n=21), and high-risk group( n=18). Conventional ultrasound parameters were collected, and 4D Auto LVQ technology was used to obtain the mechanical parameters of left ventricular myocardium, including global longitudinal strain(GLS) , global circumferential strain(GCS), global area strain(GAS), global radial strain(GRS), twist and torsion. The differences in these parameters among the four groups were compared. The predictive values of conventional ultrasound parameters and myocardial mechanical parameters in patients with intermediate- and high-risk HCM patients were analyzed by ROC curve. Results:①Left ventricular end-diastolic diameter, left ventricular end-diastolic volume, left ventricular end-systolic volume, and peak systolic velocity of mitral annulus in the low-, intermediate-, and high-risk groups were lower than those in the control group while left ventricular maximal wall thickness(LVMWT) and early diastolic peak velocity of mitral value orifice/early diastolic peak velocity of mitral annulus(E/e′) were higher, left atrial diameter(LAD) and left ventricular outflow tract gradients(LVOTG) in the intermediate- and high-risk groups were higher than the low-risk group(all P<0.05). ②Compared with the control group, the GLS of HCM patients was lower, and the GLS of the intermediate- and high-risk groups was lower than the low-risk group. GCS and GRS in the intermediate- and high-risk groups were lower than those in the low-risk group. GAS in the high-risk group was lower than the low-risk and the control group, but higher than the intermediate-risk group(all P<0.05). Compared with the control group, the twist and torsion in the intermediate- and high-risk groups were higher, but lower than the low-risk group, and the differences were statistically significant(all P<0.05). ③The ROC results showed that the area under the curve(AUC) of the model containing conventional ultrasound parameters(LVWMT, LAD, and LVOTG) for predicting intermediate- and high-risk HCM patients was 0.811, with a sensitivity of 0.769 and a specificity of 0.755. The AUC of the conventional ultrasound parameters combined with myocardial mechanical parameters was 0.904, as the sensitivity was 0.667 and the specificity was 0.980. Conclusions:4D Auto LVQ can evaluate the mechanical characteristics of LV myocardium in HCM patients with different risk stratifications. Myocardial mechanical parameters combined with conventional ultrasound parameters can improve the diagnostic performance of patients with intermediate- and high-risk HCM.
摘要
Neuropathic pain is a clinical symptom with complex mechanisms and high incidence. The commonly used analgesics have limited efficacy and can cause serious side effects. The theory of chronic pain entering collaterals was proposed by YE Tianshi, a famous physician focusing on warm diseases in the Qing dynasty, on the basis of the ancient therapies for pain. This theory is particularly suitable for the diagnosis and treatment of neuropathic pain in view of the clinical course and manifestations. The chronic neuropathic pain can enter the Yin collateral in deeper sites. The pathogenesis of neuropathic pain is summarized as a deficiency in origin and excess in superficiality. The root cause is the dysfunction of Zang-Fu organs, mainly the liver, kidney and heart, while the superficial causes are phlegm and stasis caused by the obstructed Qi and blood movement due to the consumption of Qi and blood in collaterals. Accordingly, the therapies such as dispelling blood stasis, resolving phlegm, and dredging collaterals should be adopted. This paper expounds the traditional Chinese medicine (TCM) pathogenesis and treatment of neuropathic pain, enriching the knowledge and providing new ideas for the TCM prevention and treatment of this disease as a collateral disease.
摘要
Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.
Subject(s)
Chromatography, High Pressure Liquid , Drugs, Chinese Herbal/standards , Quality Control摘要
OBJECTIVE@#To delineate the onset and recurrence characteristics of noncardiogenic ischemic stroke patients in China.@*METHODS@#A prospective, multicenter and registry study was carried out in 2,558 patients at 7 representative clinical sub-centers during November 3, 2016 to February 17, 2019. A questionnaire was used to collect information of patients regarding CM syndromes and constitutions and associated risk factors. Additionally, stroke recurrence was defined as a primary outcome indicator.@*RESULTS@#A total of 327 (12.78 %) patients endured recurrence events, 1,681 (65.72%) were men, and the average age was 63.33 ± 9.45 years. Totally 1,741 (68.06%) patients suffered first-ever ischemic stroke, 1,772 (69.27%) patients reported to have hypertension, and 1,640 (64.11%) of them reported dyslipidemia, 1,595 (62.35%) patients exhibited small-artery occlusion by The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Specifically, 1,271 (49.69%) patients were considered as qi-deficient constitution, and 1,227 (47.97%) patients were determined as stagnant blood constitution. There were 1,303 (50.94%) patients diagnosed as blood stasis syndrome, 1,280 (50.04%) patients exhibited phlegm and dampness syndrome and 1,012 (39.56%) patients demonstrated qi deficiency syndrome. And 1,033 (40.38%) patients declared intracranial artery stenosis, and 478 (18.69%) patients reported carotid artery stenosis. The plaque in 1,508 (41.36%) patients were of mixed. Particularly, 41.09% of them demonstrated abnormal levels of glycated hemoglobin levels.@*CONCLUSIONS@#Recurrence in minor and small-artery stroke cannot be ignored. Hypertension, dyslipidemia, abnormal HbA1c, intracranial artery stenosis and carotid plaque were more common in stroke patients. Particularly, phlegm-dampness and blood stasis syndromes, as well as qi deficiency and blood stasis constitutions, were still the main manifestations of stroke. (Trial registration at ClinicalTrials.gov No. NCT03174535).
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Constriction, Pathologic , Hospitals , Hypertension , Ischemic Stroke , Medicine, Chinese Traditional , Prospective Studies , Stroke/epidemiology , Syndrome摘要
Objective:To observe the effects of self-regulation combined with health education on postoperative deep vein thrombosis (DVT) and emotion in patients with cerebral hemorrhage, so as to provide reference for the formulation of clinical nursing plan.Methods:A total of 118 patients with cerebral hemorrhage underwent surgery in Qinghai Provincial People′s Hospital from January 2019 to January 2020 were enrolled, and divided into two groups by random number table method, each group with 59 cases. The patients in the routine group received routine nursing and health education and the patients in the combined group received self-regulation based on the routine group. Then the cerebral edema, hematoma volume, National Institutes of Health Stroke Scale (NIHSS) score, Self-rating Anxiety Scale(SAS) score, Self-rating Depression Scale (SDS) score, postoperative DVT rate, and blood coagulation indexes were compared between the two groups.Results:There was no significant difference in the cerebral edema, hematoma volume, NIHSS score, SAS score, SDS score before nursing between the two groups( P>0.05). After nursing, the cerebral edema volume, hematoma volume and NIHSS score were (16.42 ± 6.41) ml, (6.74 ± 0.81) ml, (11.30 ± 4.43) points in the combined group, which were lower than those in the routine group (20.44 ± 5.04) ml, (9.93 ± 1.30) ml, (15.31 ± 4.65) points, the differences were statistical significant( t=3.79, 16.00, 4.80, all P<0.05). The SAS and SDS scores after nursing were (37.21 ± 2.71), (41.32 ± 3.26) points in the combined group, which were significantly lower than those in the routine group (45.23 ± 4.65), (46.56 ± 4.66) points, the differences were statistical significant ( t=11.45, 7.08, both P<0.05). The incidence of DVT during nursing in the combined group was 1.69%(1/59), which was significantly lower than that in the routine group 13.56%(8/59), the difference was statistical significant ( χ2=4.33, P<0.05). The prothrombin time, thrombin time, activated partial thrombin time and fibrinogen had no significant difference after nursing between the two groups ( P>0.05). Conclusions:Application of self-regulation combined with health education for patients with cerebral hemorrhage can effectively alleviate the negative emotions, ameliorate the neurologic deficits, cerebral hematoma and cerebral edema, and prevent DVT of lower extremity without affecting blood coagulation indexes of patients.
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Objective: To evaluate the efficacy within the first 24 h post extracorporeal membrane pulmonary oxygenation (ECMO) and the impact of early efficacy on the prognosis of adult patients with fulminant myocarditis (FM). Methods: This retrospective case analysis study included hospitalized patients (age≥18 years) who were diagnosed with fulminant myocarditis from November 2016 to May 2021 in the First Affiliated Hospital of Zhengzhou University. Patients were divided into survival or non-survival groups according to treatment outcomes. The age, sex, treatments, drug use, ECMO use, clinical and laboratory data (before and 24 h after the use of ECMO) were analyzed. The change rate of clinical and laboratory data after 24 h use of ECMO was calculated to find differences between two groups. Multivariate logistic regression was used to analyze the related factors with in-hospital death and complication between the two groups. Results: A total of 38 FM patients treated with ECMO were included. There were 23 cases (60.5%) in the survival group, aged (39.6±13.7) years, and 17 (73.9%) cases were female. The total ECMO time was (134.4±71.3)h. There were 15 cases (39.5%) in non-survival group, aged (40.0±15.8) years, and there were 12(80.0%) female, the ECMO time was (120.1±72.4) h in this group. The proportion of tracheal intubation and continuous renal replacement therapy in the survivor group and dosage of norepinephrine within 24 h after ECMO implantation were significantly less than in non-survival group (all P<0.05). There was no significant difference in all efficacy related biochemical indexes between two groups before ECMO use. The levels of lactic acid, procalcitonin, creatinine, alanine aminotransferase, aspartate aminotransferase, creatine kinase-MB, cardiac troponin I and N-terminal B-type natriuretic peptide prosoma were significantly less in survival group than in non-survival group at 24 h after the use of ECMO (all P<0.05). Results of multivariate logistic regression analysis showed that the higher 24 h change rate of creatinine (OR=0.587, 95%CI 0.349-0.986, P=0.044) and creatine kinase-MB (OR=0.177, 95%CI 0.037-0.841, P=0.029) were positively correlated with reduced risk of in-hospital mortality. The central hemorrhage and acute kidney injury in survival group were less than in non-survivor group (P<0.05). Conclusions: After 24 h early use of ECMO in FM patients, the improvement of various efficacy related biochemical test indexes in the survival group was better than that in the non-survival group. Faster reduction of creatine kinase-MB and creatinine values within 24 h ECMO use is positively correlated with reduced risk of in-hospital mortality in adult patients with FM.
Subject(s)
Adolescent , Adult , Female , Humans , Middle Aged , Young Adult , Extracorporeal Membrane Oxygenation/methods , Hospital Mortality , Myocarditis/therapy , Retrospective Studies , Treatment Outcome摘要
Objective: To investigate the clinicopathological features as well as BRAF V600E and MYD88 L265P mutation status of nodal marginal zone B cell lymphoma (NMZL). Methods: Thirty-two cases of NMZL were diagnosed from September 2009 to February 2021 at the Henan Provincial People's Hospital and Peking University School of Basic Medical Sciences. The clinicopathologic characteristics were obtained and analyzed. BRAF V600E and MYD88 L265P mutation status were identified using PCR and Sanger sequencing, respectively. Results: There were 20 males and 12 females patients with a median age of 69 years (ranging 36-82 years). The most prevalent clinical manifestation was multiple lymph nodes enlargement in head and neck (22/32, 68.8%), followed by inguinal (12/32, 37.5%), axillary (11/32, 34.4%), mediastinum (5/32, 15.6%) and retroperitoneal lymph nodes (4/32, 12.5%). Most of the patients were in Ann Arbor stage Ⅰ/Ⅱ (21 cases). The morphologic features included diffuse (24/32, 75.0%), nodular (5/32, 15.6%), interfollicular (2/32,6.3%) and perifollicular (1/32,3.1%) types. The tumor cells showed monocyte-like, centrocyte-like, small lymphocyte-like and plasma cell-like differentiation. Immunophenotyping revealed diffuse expression of CD20 in all tumor cells, whereas CD43 (11/32, 34.4%), bcl-2 (20/32, 62.5%), MNDA (13/32, 40.6%) and CD5 (2/32, 6.3%) were partially expressed. Ki-67 proliferation index varied from 10% to 40%. BRAF V600E mutation was found in two cases (2/32, 6.3%), but MYD88 L265P mutation was not detected. Eighteen patients survived and three died at the end of follow-up period which ranged 6 to 110 months. Conclusions: The morphologic features of NMZL varies across individuals, it should be differentiated from various B-cell lymphomas; however immunological biomarkers with high specificity for NMZL are still lacking. No MYD88 L265P mutation is found in NMZL. Some cases may harbor BRAF V600E mutation and yet the prevalence remains indeterminate; further researches are warranted.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Lymphoma, B-Cell, Marginal Zone/pathology , Mutation , Myeloid Differentiation Factor 88/genetics , Polymerase Chain Reaction , Proto-Oncogene Proteins B-raf/genetics摘要
Objective: To explore the clinical features of hepatocerebral mitochondrial DNA depletion syndrome (MDS). Methods: The clinical data of 6 hepatocerebral MDS patients diagnosed in the Jinshan Hospital of Fudan University from January 2012 to December 2019 were retrospectively collected and analyzed. Related literature published before January 2020 were searched with the key words of "DGUOK""MPV17""POLG""C10orf2" in PubMed, China national knowledge infrastructure (CNKI) and Wanfang database. Results: All the 6 hepatocerebral MDS cases were male. The age of onset ranged from 3 days to 8 months. The most common initial symptoms were cholestasis and developmental retrogression. The main clinical manifestations included hepatomegaly (4 cases), hypotonia (3 cases), growth retardation (4 cases), cholestasis (5 cases), coagulopathy (5 cases), hypoalbuminemia (3 cases), hypoglycemia (4 cases), hyperlactacidemia (5 cases), and abnormal blood metabolism screening (6 cases). The isotope hepatobiliary imaging revealed no gallbladder and intestinal tract development within 24 hours in 2 patients. Regarding the cranial imaging examination, the head CT found widening of the extracranial space in 1 case, the brain magnetic resonance imaging (MRI) found ventricular enlargement in 2 cases, and the brain ultrasound found peripheral white matter injury in 1 case. Two cases were lost to follow-up, one died of liver failure, and three died of multiple organ failure due to aggravated infection. Among the 6 cases, there were 3 with MPV17 variation (c.182T>C and c.279G>C were novel), 1 with POLG variation (c.2993G>A was novel), 1 with DGUOK variation (c.679G>A homozygous mutation, parthenogenetic diploid of chromosome 2) and 1 with C10orf2 variation (c.1186C>T and c.1504C>T were novel). The literature review found that 129, 100, 51 and 12 cases of hepatocerebral MDS were caused by DGUOK, MPV17, POLG and C10orf2 gene variations, respectively. And the most common clinical manifestations were liver dysfunction presented with cholestasis and elevated transaminase, metabolic disorders including hypoglycemia and hyperlactacidemia, and diverse neurologic symptoms including developmental retardation, hypotonia, epilepsy and peripheral neuropathy. Besides, 1/3 of the patients with C10orf2 variation developed renal tubular injury. Conclusions: Hepatocerebral MDS mainly present with liver dysfunction, metabolic disorder and neuromuscular impairment. Different genotypes show specific clinical manifestations.
Subject(s)
Female , Humans , Infant , Male , Cholestasis , DNA, Mitochondrial/genetics , Hypoglycemia/genetics , Liver Diseases/genetics , Mitochondrial Diseases , Muscle Hypotonia , Retrospective Studies摘要
The present study aimed to explore the correlation between agronomic traits and quality indexes of Dendrobium nobile and its application value in agricultural breeding. The cultivated strains of D. nobile in Hejiang-Chishui producing areas were extensively collected,and the main agronomic traits and quality indexes were measured. The agronomic traits with significant correlation with quality indexes were screened out by the correlation analysis,and then the parental lines and self-bred F_1 generation plants were furtherverified. Among 96 lines of D. nobile,the content of soluble polysaccharides showed a significant negative correlation with dendrobine( P < 0. 01),and no significant correlation with agronomic traits in stems and leaves. The content of dendrobine exhibited a significant positive correlation with the stem width-thickness ratio( at the largest cross section; P < 0. 01),and no significant correlation with other agronomic traits. Regression analysis further verified the positive correlation between dendrobine content and stem width-thickness ratio( R2> 0. 9). Two lines,JC-10 and JC-35,with significant differences in stem width-thickness ratio were screened out( P <0. 05). The corresponding F1 generation plants by self-pollination both showed that the dendrobine content was higher with greater stem width-thickness ratio( P < 0. 01). The experimental results suggested that within a certain range,the dendrobine content was higher in D. nobile with flatter stem. Therefore,in the breeding of D. nobile,this specific trait could be used for screening plants with high content of quality indexes such as dendrobine.
Subject(s)
Agriculture , Dendrobium/genetics , Plant Breeding , Plant Leaves/genetics , Polysaccharides摘要
Network pharmacological approaches were used to predict the components, targets and pathways of Erhuang decoction (EhD) in the treatment of acute lung injury (ALI). The SwissTargetPrediction platform, DisGeNET, Therapeutic Target Database (TTD), GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were used to predict potential targets of EhD and were integrated with the predicted targets for the treatment of ALI. A protein-protein interaction network model was constructed by using String database and Cytoscape software; the DAVID platform was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of drug components-targets-pathways was constructed by Cytoscape software and the SwissDock platform was used to dock the molecules of EhD found in blood with the key disease targets. An ALI model was established in mice and inflammatory factor detection and Western blot protein expression experiments with lung tissue sections were carried out to verify the effect of EhD in the treatment of ALI. Animal experiment ethical requirements were approved by the Ethical Committee Experimental Animal Center of Shandong University (Grant Number: 2016020). We identified 148 potential targets including signal transducer and activator of transcription 3 (STAT3), vascular endothelial cell growth factor A (VEGFA), RAC-alpha serine/threonine-protein kinase (AKT1), and nuclear factor-kappa B/p65 (RELA). The potential targets are largely associated with the biological processes of inflammation, oxidative stress, and apoptosis. Additional pathways relate to cancer, VEGF signaling, mitogen-activated protein kinase (MAPK) signaling, and Toll-like receptors (TLRs) signaling, along with other signaling pathways. Pharmacodynamic experiments showed that EhD could significantly reduce the content of inflammatory factors and the degree of lung injury of ALI mice. Western blot revealed that EhD could significantly decrease the expression of NF-κB/p65 and upregulate the expression of NF-kappa-B inhibitor alpha (IκBα). From the perspective of network pharmacology, the mechanisms of EhD in the treatment of ALI is consistent with the characteristics of multiple ingredients, multiple targets and multiple pathways. This research provides a reference for further study of the mechanism of this traditional Chinese medicine.
摘要
Purpose@#We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH). @*Materials and Methods@#A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib. @*Results@#The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO– group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients. @*Conclusion@#Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.
摘要
BACKGROUND@#Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.@*METHODS@#We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.@*RESULTS@#Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.@*CONCLUSIONS@#NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
Subject(s)
Humans , Apoptosis/genetics , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Liver Neoplasms/genetics , Nuclear Proteins , Prognosis摘要
OBJECTIVE@#To explore the effects of Eriodictyol to the growth, apoptosis and oxidative stress of Burkitt lymphoma (BL) cells and phosphorylation of protein kinase B (AKT) in children.@*METHODS@#The effects of Eriodictyol (0, 1.25, 2.5, 5, 10, 20, 40, 80, 160, 320 μmol/L) to viability of BL cell line DG-75 cells were detected by CCK-8. The effects of Eriodictyol (0, 10, 20, 40 μmol/L) to the proliferation activity of DG-75, apoptosis rate, levels of apoptosis-related proteins, oxidative stress indexes [superoxide dismutase (SOD), malondialdehyde (MDA)], mitochondrial membrane potential (MMP) and phosphorylation level of phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycinm (mTOR) were detected by clony formation assay and Wester blot.@*RESULTS@#When the treatment concentration of Eriodictyol was 20 μmol/L, the proliferation activity of the cells was decreased (P<0.05). The concentrations at 10, 20, 40 μmol/L were selected for subsequent experiments. Compared with 0 μmol/L Eriodictyol, the proliferation activity of DG-75, SOD activity, MMP, phosphorylation levels of PI3K, AKT and mTOR in 20 and 40 μmol/L Eriodictyol treatment groups were significantly decreased (P<0.05), while cells apoptosis rate, Cleaved-Caspase-3/Caspase-3, Bax/Bcl-2 and MDA level were significantly increased (P<0.05).@*CONCLUSION@#Eriodictyol may promote the mitochondrial apoptosis pathway by inhibiting the abnormal activation of PI3K/AKT/mTOR to reduce the proliferation activity of DG-75, and inhibit oxidative stress response to increase the apoptosis rate and play anti-tumor roles.
Subject(s)
Apoptosis , Flavanones , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction摘要
Objective:To investigate the effect of ultrasound-guided stellate ganglion block (SGB) in patients undergoing radical mastectomy, and to provide an effective reference for the selection of clinical anesthesia.Methods:A total of 86 patients undergoing radical mastectomy for breast cancer in the First Affiliated Hospital of Hunan Traditional Chinese Medicine College from January 2018 to December 2019 were selected as the research objects and randomly divided into two groups, with 43 cases in each group. On the basis of conventional general anesthesia, the observation group was treated with ultrasound-guided SGB intervention at the level of the sixth cervical vertebra on the left, and 0.5% ropivacaine was injected with 7 ml. The control group was treated with ultrasound-guided injection of equal volume normal saline at the same site. The hemodynamics and serum inflammatory factors, cellular immunity, prostaglandin E 2 (PGE 2), substance P (SP), serotonin (5-HT) expression, cerebral oxygen metabolism indexes before anesthesia induction (T 1), before intubation (T 2), immediately after intubation (T 3), during skin incision (T 4) and extubation (T 5), and cognitive function score before and after surgery of the two groups were measured respectively. Results:⑴ Hemodynamics: the heart rate (HR) and mean arterial pressure (MAP) of the observation group at T 2, T 3, T 4 were lower than those of the control group ( P<0.05), and there was no significant difference between the two groups at T 1, T 5 ( P>0.05). ⑵ Inflammation and immune status: there was no significant difference in interleukin (IL)-2, IL-18, tumor necrosis factor-α (TNF-α), CD3 + , CD4 + and CD8 + between the two groups at T 1, T 5 ( P>0.05); the IL-2, IL-18, TNF-α and CD8 + at T 2, T 3 and T 4 in the observation group were lower than those in the control group, while the CD3 + and CD4 + were higher than that in the control group ( P<0.05). ⑶ Pain mediators and cerebral oxygen metabolism indexes: there was no significant difference in the levels of PGE 2, SP, 5-HT, SjvO 2, Da-jvO 2 and CEO 2 between the two groups at T 1 and T 5 ( P>0.05); The levels of PGE 2, SP, 5-HT, Da-jvO 2 and CEO 2 in the observation group at T 2, T 3 and T 4 were lower than those in the control group, and the SjvO 2 was higher than those in the control group ( P<0.05). ⑷ Cognitive function: there was no significant difference in Mini Mental State Examination (MMSE) scores between the two groups at 1 day before and 5 days after operation ( P>0.05). At 1 and 3 days after operation, the MMSE score of the observation group was higher than that of the control group ( P<0.05). Conclusions:Ultrasound-guided SGB has a good application effect in patients undergoing radical mastectomy and can reduce the fluctuation of intraoperative hemodynamics, intraoperative inflammatory stress and immunosuppressive effects of the body, reduce the release of pain mediators, and at the same time improve cerebral oxygen metabolism, and promote postoperative cognitive function recovery.