National Medical Journal of China
Volume 98 · Issue 16 · 2018
Natl Med J China
To standardize the clinical diagnosis and treatment of benign paroxysmal positional vertigo
It is the deepening understanding and effective treatment of benign paroxysmal positional vertigo (BPPV) that promotes the upsurge of diagnosis and treatment of dizziness/vertigo at home and abroad. At present, the domestic situation is that on the one hand, there is insufficient understanding of BPPV, and on the other hand, there is generalization of BPPV diagnosis and treatment, which will affect the sustainable development of dizziness/vertigo diagnosis, treatment and research or may lead to misdiagnosis and mistreatment. It is urgent to clarify some key issues and standardize the clinical diagnosis and treatment of benign paroxysmal positional vertigo.
Chemotherapy management of breast cancer in the era of precision medicine
In 2015, the United States announced a new project in the field of life sciences-the Precision Medicine Plan, and then the Chinese government also launched the Precision Medicine Plan. It should be said that precision medicine is an individualized medical model developed based on empirical medicine model and evidence-based medicine model. Tumors are polygenic diseases and are the best objects for precision medicine research. Precision medicine of tumors includes accurate early diagnosis, molecular typing, efficacy prediction and monitoring, metastasis and recurrence monitoring, and prognosis judgment. Classification treatment under the guidance of molecular typing of breast cancer is the representative of precision medicine.
Mastering, standardization and reasonable application of bedside examination of the vertigo
The etiology of vertigo/dizziness is complex and involves multiple disciplines. From the general outpatient department of primary hospitals to the relevant specialty outpatient and emergency department of tertiary hospitals, a large number of vertigo/dizziness patients are admitted every year. Clinicians at all levels are required to have comprehensive knowledge of vertigo/dizziness related disciplines, excellent medical history inquiry skills, basic skills of physical examination, and the ability to reasonably select and correctly interpret auxiliary examinations, so as to be able to diagnose and treat correctly under different diagnosis and treatment conditions (emergency rooms, outpatient clinics or wards of different levels of hospitals). Today, with the high development of imaging technology, clinicians' dependence on auxiliary examination has obviously increased. However, physical examination, as a basic technology of doctors, is an indispensable means of disease diagnosis, and it is also the embodiment of good clinical thinking mode. Therefore, vertigo physical examination (hereinafter referred to as vertigo physical examination) as the basic skill of vertigo/dizziness diagnosis and treatment needs to be repeatedly emphasized and standardized training.
Standardization and clinical application of vestibular function examination
Vestibular function examination is indispensable in the clinical practice of diagnosis and treatment of vertigo. Vestibular function examination can achieve the following goals: confirm clinical judgment, and there will be a preliminary clinical diagnosis through medical history and clinical examination. The examination further confirms the state of vestibular function, whether it is unilateral weakening, bilateral decline, or normal vestibular function; Quantitative detection of the extent and degree of vestibular function impairment (semicircular canal, otolithic apparatus, complete and partial loss of function); Vestibular physiological evidence of functional compensation after vestibular impairment, and objective evidence of functional vertigo. Vestibular function tests include vestibular-ocular reflex function tests and vestibular-spinal reflex tests, which are used to evaluate semicircular canal (cold-hot test, shake-head nystagmus, swivel chair and cephalic pulse test), otolithic function (cervicogenic and ophthalmic vestibular-evoked myogenic potentials) and balance function, respectively.
Updates of Chinese Society of Clinical Oncology (CSCO) guideline for breast cancer in 2018
The Chinese Society of Clinical Oncology (CSCO) "Guidelines for the Diagnosis and Treatment of Breast Cancer" is a clinical diagnosis and treatment guide based on evidence-based medical evidence and the basic principles of precision medicine, combined with the cutting-edge medical progress at home and abroad, and taking into account China's medical status and resource availability. Scientific and practical are the two main principles of consideration in the guide. The diagnosis and treatment suggestions of each clinical problem are divided into two parts: basic strategy and optional strategy. The basic strategy belongs to universal diagnosis and treatment measures with good accessibility, and the value of tumor treatment is relatively stable; Most alternative strategies belong to drugs or treatment measures with high-level evidence, but poor accessibility or potency ratio beyond the affordability of Chinese people. In order to better complete the update of the 2018 edition of the guidelines, this paper analyzes and discusses the important research progress in the field of breast cancer in the past year, for the reference of the expert committee in updating the guidelines.
Clinical features and imaging characteristics of Meniere′s disease verified by intravenous gadolinium contrast-enhanced magnetic resonance imaging
To analyze the clinical features and imaging characteristics of Meniere′s disease (MD)verified by intravenous gadolinium contrast-enhanced magnetic resonance imaging(MRI).
A total of 174 patients with Meniere′s disease were involved in this study between March 2016 and October 2017. All of them underwent 3D-fluid attenuated inversion recovery (FLAIR) MRI and presented endolymphatic hydrops and clinical characteristics of suspected Meniere′s disease. The clinical characteristics, the grades of endolymphatic hydrops (EH) using Nakashima grading standard were analyzed, and the correlation between grade and clinical features was evaluated.
There were totally 174 patients (88 males, 86 females), with the age of 7-83 years [mean age of (51.0±15.0)] years. Age of onset and disease course was 7-83 years [mean age of (44.6±16.6) years], 36.0 (12.0, 111.0) months (from 2 days to 70 years), respectively. EH was found in all the patients, and 169 cases (97.1%) manifested as modest or severe hydrops. Among the 174 patients, 139 cases (79.9%) presented unilateral EH, and 35 cases (20.1%) presented bilateral EH. The degree of EH in the latter was more serious than the former. For 174 patients, clinical characteristics were inconsistent, which was not in accord with the existing diagnostic criteria. Furthermore, there was a correlation between degree of hydrops and degree of hearing loss (P<0.05).
EH in Meniere′s disease can be measured objectively by intravenous gadolinium contrast-enhanced MRI. Clinical characteristics in MD verified by EH are not accordant with the existing criteria, which means the significance of EH in diagnosis of MD. Moreover, there′s a correlation between degree and distribution of hydrops and degree of hearing loss.
Relationship between 25-hydroxyvitamin D levels and idiopathic benign paroxysmal positional vertigo in female patients
To investigate the relationship between serum 25-hydroxyvitamin D[25(OH) D] levels and idiopathic benign paroxysmal positional vertigo (BPPV) in female patients.
A total of 67 women diagnosed with idiopathic BPPV were selected as the study group between January and December 2016 in Ningbo No.2 Hospital, and 95 healthy women without a history of vertigo or dizziness were selected as the control group. The data of height, weight, histories of hypertension and diabetes mellitus were collected, and serum 25(OH) D levels were measured. The number of the recurrence and canalith repositioning maneuvers were recorded during the one-year follow-up.
No significant differences of age, body mass index, histories of hypertension and diabetes mellitus between patients with BPPV and healthy controls (all P>0.05) .The serum 25 (OH) D levels were significantly lower in patients with idiopathic BPPV than in healthy controls [(50.56±13.36) nmol/L vs (56.55±16.21) nmol/L,t=-2.485, P=0.014]. BPPV patients with low level of 25(OH) D showed a significant increase in the number of canalith repositioning maneuvers required and the recurrence rate. The regression analyses demonstrated that 25(OH)D deficiency was associated with BPPV with an odds ratio of 2.054 (95% CI: 1.088-3.877, P=0.026).
25(OH) D deficiency may be a risk factor of BPPV.
Etiological analysis on patients with vertigo or dizziness
To explore the spectrum of causes for patients with vertigo or dizziness in the Department of Neurology, and provide a reference for diagnosis and treatment of patients with vertigo or dizziness.
Clinical data of patients in the Department of Neurology, Baotou Central Hospital between January 2016 and September 2017 was retrospectively analyzed. The target group under study was diagnosed based on the uniform diagnostic criteria.
A total of 9 200 patients with a chief complaint of vertigo or dizziness were included. The ratio of male to female was 1∶1.8, with an age range of 19 to 85 years. The different etiology was as follows: benign paroxysmal positional vertigo (BPPV) (3 148 cases, 34.22%), persistent postural-perceptual dizziness (PPPD) (2 006 cases, 21.80%), vertigo caused by cerebrovascular diseases (1 463 cases, 15.90%), vestibular neuritis (741 cases, 8.05%), vestibular migraine (536 cases, 5.83%), vestibular paroxysmia (336 cases, 3.65%), Ménière disease (187 cases, 2.03%), drug-induced vertigo (96 cases, 1.04%), neurological degenerative diseases (74 cases, 0.80%), sudden sensorineural hearing loss (51 cases, 0.55%), multiple sclerosis and neuromyelitis optica (21 cases, 0.23%), other reasons (22 cases, 0.24%), unknown reasons (519 cases, 5.64%).
Dizziness is resulted from various causes, and BPPV is the most common reason. Vertigo caused by cerebrovascular diseases appears to gradually increase along with age. PPPD is very common in clinical practice, so clinicians needs to be highly aware of BPPV and PPPD. Although those dizziness diseases have a low incidence, they should not be ignored. There are still certain proportion of vertigo patients whose diagnosis are undetermined.
A multicenter, randomized, controlled, phase Ⅳ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer
To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer.
There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy.
In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%.
The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.
Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer
To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB.
This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m2/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m2/21d) until the disease progression or the intolerance toxicity.
From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1—23) and a median of 260mg/m2 actual drug dose (range 220-260 mg/m2). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m2 reduce to 220 mg/m2). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA).
The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.
Effect of single nucleotide polymorphisms of RS1826690 located in UGT2B4 gene on the pathological complete response to neoadjuvant chemotherapy in breast cancer patients
To evaluate the association between single nucleotide polymorphisms (SNPs) of RS1826690 located in UGT2B4 gene and pathological complete response (pCR) to neoadjuvant chemotherapy in breast cancer patients.
A total of 146 breast cancer patients were enrolled to detect the SNPs of RS1826690 by sequenom. The relationship between SNPs of RS1826690 and pCR, predictors of pCR were analyzed by univariate or multivariate analysis.
The frequency of CC, CT and TT genetype of RS1826690 was 20.6%, 39.7% and 39.7%, respectively. Of the 171 patients, pCR was achieved in 39 cases (26.7%), with CC allele in 14 cases, CT allele in 7 cases and TT allele in 18 cases, and statistically significant difference was observed (χ2=16.684, P=0.003). Multivariate logistic regression analysis showed that SNPs of RS1826690 was an independent predictor of pCR (95% CI: 2.311-28.810, P=0.001) . SNPs of RS1826690 was statistically associated with estrogen receptor (ER) status (χ2=7.872, P=0.020).
SNPs of RS1826690 was associated with pCR, and breast cancer patients with CC allele were more likely to achieve pCR.
Clinical observation of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer
To assess the clinical efficacy and adverse outcomes of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer.
A total of 24 patients with multi-drug-resistant advanced breast cancer who underwent apatinib mesylate treatment were retrospectively analyzed at the Diagnosis and Treatment Center for Breast Cancer of Henan Cancer Hospital. Patients were reviewed every 4 weeks after initial treatment and then every 8 weeks after stable disease. Objective response rate (ORR), progression free survival (PFS), overall survival (OS) , toxicity and adverse outcomes of apatinib mesylate treatment were evaluated by imaging examinations.
Totally, 24 patients received apatinib mesylate at a dose of 500 mg QD. Out of the 24 patients treated, complete remission (CR) occurred in none of the patients, partial remission (PR) in 10 cases, stable disease (SD) in 10 cases, progressive disease (PD) in 4 cases, and drug with drawal in 2 cases due to adverse outcomes. Treatment with apatinib mesylate resulted in an ORR of 41.7% (10/24), disease control rate (DCR) of 83.3%, PFS of 4.7 months, and OS of 8.0 months. Adverse outcomes included proteinuria, high blood pressure, fatigue, hand-foot skin reaction (HFSR), hyperbilirubinemia, leukopenia, hair/skin pigmentation decreased. Most of the adverse events were tolerable and can be controlled after symptomatic management.
Single-agent apatinib mesylate demonstrated the good short-term efficacy for multi-drug resistant advanced breast cancer in patients who previously underwent multiple line treatment failures. Adverse effects were controllable after symptomatic management. Treatment with apatinib mesylate maybe a viable option when other treatment modalities failed.
Prognostic significance of inflammatory indicators for advanced-stage diffuse large B-cell lymphoma
To explore the prognostic significance of inflammatory indicator, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), for advanced-stage diffuse large B-cell lymphoma (DLBCL).
The data of advanced stage DLBCL cases was retrospectively collected, and all the patients were seen from January 2006 to December 2012 in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences. The patients were divided into the low NLR group (≤5∶1) and the high NLR group (>5∶1); the low PLR group (≤300∶1) and the high PLR group (>300∶1). Kaplan-Meier method was used to compare the survival rates between groups, multivriate Cox proportional hazard regression analysis was performed to assess the independent prognostic significance of clinical and histopathological variables on events or OS.
A total of 361 patients were included in the study. Under a median follow-up of 89 months, the 5-year overall survival (OS) and progression-free survival (PFS) of the whole group were 42.9% and 31.3%, respectively. The 5-year OS rate and PFS rate were 48.2% and 35.1% in the low NLR group, which were 24.1% and 17.7% in the high NLR group, respectively. The 5-year OS rates and PFS rate were 45.4% and 33.2% in the low PLR group, which were 29.8% and 21.1% in the high PLR group (all P<0.05). Univariate analysis showed that NLR >5∶1, PLR >300∶1, age>60 year, ECOG PS>1 score, stage Ⅳ, B symptom, bulky disease, number of extranodal sites >1, Ki-67index >90%, LDH elevated and β2-MG elevated had significant influence on prognosis(allP<0.05). Multivariate analysis demonstrated that NLR, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index and β2-MG were associated with poor prognosis in the advanced-stage DLBCL.
NLR was simple and feasible biomarker for prognosis of advanced-stage DLBCL patients
Value of PET/CT in the prognosis of extranodal NK/T cell lymphoma
To explore the value of Positron-Emission Tomography/Computed Tomography (PET/CT) in the prognosis of extranodal NK/T cell lymphoma.
The patients of NK/T cell lymphoma diagnosed from January 2007 to July 2016 in Department of Pathology of Beijing Tongren Hospital were enrolled in this study. Seventy-two in-hospital patients were examined on the invasion of adjecent tissue or organ by PET/CT. The PET/CT results were analyzed retrospectively. Kaplan-Meier method was used to analyze the prognostic value of the positive results by PET/CT on overall survival (OS).
There were 54 males and 18 females with median age of 44.5 years (13-75 years). According to Ann Arbor staging system, there were 16 cases (22.2%) in stage Ⅰ, 29 cases (40.3%) in stage Ⅱ, 6 cases (8.3%) in stage Ⅲ and 21 cases (29.2%) in stage Ⅳ. According to the IPI scoring system, there were 34 cases (47.2%) in the low risk group (0-1 point), 21 cases (29.2%) in the low-middle risk group (2 points), 16 cases (22.2%) in the middle-high risk group (3 points), and 1 case (1.4%) in the high risk group (4-5 points) . The median follow-up time was 29.2 months (1-118 months). The disease occured in unilateral nasal cavity in 26 cases (36.1%), bilateral nasal cavities in 36 cases (50.0%), nasopharynx, oropharynx and pharynx in 10 cases (13.9%). The tumors of 51 cases involved the surrounding tissue, including nasal wings in 29 cases (40.3%), nasal sinus in 29 cases (40.3%), maxillofacial soft tissue in 18 cases (25.0%), orbital in 12 cases (16.7%), maxilla and skull base in 8 cases (11.1%), eyelid in 6 cases (8.3%), brain tissue in 3 cases (4.2%), eyeball in 2 cases (2.8%). In addition, cervical and inguinal lymphadenopathy were found in 54 cases (75.0%) . Splenomegaly and hepatomegaly were found in 10 cases (13.9%) and 2 cases (2.8%), respectively. Survival analysis showed that the clinical stage and IPI were significantly associated the clinical prognosis (P=0.000, 0.001, respectively). Involvement of the maxillofacial soft tissue, eyelid, orbital, maxilla and skull base and brain tissue were significantly related to reduced the overall survival time (P=0.006, 0.000, 0.024, 0.001 and 0.015, respectively). Involvement of palate or tonsil, the nosewingand nasal sinus did not show significant shorter overall survival (P=0.091, 0.063, and 0.139, respectively). Cox regression multivariate analysis showed maxilla and skull base involvement was independent adverse prognostic factor (P=0.047).
The PET/CT examination can accurately detect the extent of adjacent and distant tissues of tumor involvement of NK/T cell lymphoma by showing the tumor structure and metabolic status, thus has important value in the clinical staging and prognosis predication.
Abnormal expression of angiopoietin-2 associated with invasion, metastasis and prognosis of lung cancer
To investigate the relationship between abnormal angiopoietin-2 (Ang-2) expression and invasion/metastasis of lung cancer.
Totally 122 cases of postoperative primary lung cancer tissues and their paracancerous tissues from Jan. 2009 to Dec. 2010 were collected from Affiliated Hospital of Nantong University and Ang-2 expression was analyzed by immunohistochemistry. At the cellular level, the protein and mRNA levels of Ang-2 in lung epithelial cell line Beas-2B and four lung cancer cell lines (SPCA-1, NCI-1650, A549 and NCI-H1975) were observed. The most effective Ang-2-shRNA for Ang-2 transcription was screened and transfected into A 549 lung cancer cells. The Ang-2 expression, Ang-2 gene transcription, cell proliferation, invasion/metastasis, and epithelial-mesenchymal transition (EMT) abilities of lung cancer cells were analyzed by Western blotting, fluorescent quantitative reverse transcriptase PCR, Cell Counting Kit-8 assay, and Transwell cell models for exploring the relationship between Ang-2 expression and invasion/metastasis of lung cancer.
The higher Ang-2 expression levels in lung cancerous tissues were closely related to tumor diameter (P=0.008), differentiating degree (P=0.033), TNM stage (P=0.025) and 5-year survival rate (P<0.001). According to the Kaplan-Meier survival curves, the 5-year survival rate of patients with higher expression levels of Ang-2 (16.1%) was significantly poorer than that of patients with lower Ang-2 (80.0%,P<0.001). Significant difference of 5-year survival rate was found in patients with different Ang-2 levels at TNM stage Ⅰ(P<0.001), but not at stage Ⅱ, Ⅲ and Ⅳ. Among Beas-2B and four lung cancer cell lines, the protein and mRNA levels of Ang-2 in A549 cells were the highest. After Ang-2-shRNA-1 plasmid successfully transfected into A549 cells, cell proliferation rate was significantly lower than that in the shRNA-negative or blank group at a time-dependent manner. The significant decrease of the invasion, migration and EMT abilities were also found in A549 cells after transfection of Ang-2 shRNA.
Abnormal expression of Ang-2 is closely related to invasion, migration and prognosis of lung cancer, and interfering the activation of Ang-2 would be a novel molecular-targeted therapy for lung cancer.
Value of procalcitonin in predicting the severity and prognosis of neonates with septicemia
To explore the value of procalcitonin(PCT) in predicting the severity and prognosis of neonates with septicemia.
The clinical data of the hospitalized neonates over the age of 72 hours with double positive blood cultures from December 1st, 2011 to September 30, 2017 at the neonatal intensive care unit of Children′s Hospital Affiliated to Capital Institute of Pediatrics was analyzed retrospectively.
A total of 75 neonates were included in the study. There was a significant negative correlation between PCT and neonatal critical illness score (r=-0.440, P<0.05). Among the groups of non-critical, critical and extremely critical, the levels of PCT had significant difference [0.27(0.10-2.55), 4.34(1.24-20.32), 19.49(1.92-106.49)μg/L,H=20.717, P<0.01]. At a cut-off point of 0.56 μg/L, PCT showed 88.6% sensitivity and 61.3% specificity for critical group diagnosis, with optimal area under the curve of 0.804 (P<0.05). At a cut-off point of 11.45 μg/L, PCT showed 65.2% sensitivity and 82.7% specificity for extremely critical group diagnosis, with optimal area under the curve of 0.735 (P<0.05). Among the groups of none organ dysfunction, single organ dysfunction and shock or multiple organ dysfunction, the levels of PCT had significant difference[0.10(0.43-2.56), 3.18(0.67-20.95), 18.97(1.92-82.90) μg/L,H=20.299, P<0.01]. At a cut-off point of 2.64 μg/L, PCT showed 70.0% sensitivity and 77.1% specificity for single organ dysfunction diagnosis, with optimal area under the curve of 0.793 (P<0.05). At a cut-off point of 9.06 μg/L, PCT showed 61.3% sensitivity and 86.4% specificity for shock or multiple organ dysfunction diagnosis, with optimal area under the curve of 0.782 (P<0.05). PCT levels were significantly higher in the death group than the survival group. At a cut-off point of 75.65 μg/L, PCT showed 80.0% sensitivity and 90.0% specificity for the judgment of death, with optimal area under the curve of 0.886 (P<0.05). C-reactive protein (CRP), white blood cell (WBC) and neutrophil lymphocyte ratio (NLR) had no significant difference in the severity and the degree of organ dysfunction of neonates with septicemia(allP>0.05).
Compared to CRP, WBC and NLR, PCT has high value in predicting the severity, the degree of organ dysfunction and the prognosis of neonates with septicemia.
Effects of glycyrrhizic acid on ERK1/2 and p38 MAPK signaling pathway in a murine model of asthma
To explore the effects of glycyrrhizic acid (GA) on Extracellular regulated protein kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK) signaling pathways in a murine model of asthma.
Sixty female BALB/c mice were randomly divided into 6 groups (n=10 each): a control group, an asthmatic group, two treatment groups with low and high doses of GA, U0126 group and SB203580 group. Within 24 hours after the last OVA challenge, histological studies of lung were conducted with the hematoxylin and eosin staining (HE) and alcian blue-periodic acid-Schiff (AB-PAS), the relative protein expression of ERK1/2 and p38 MAPK were detected by immunohistochemistry and Western blotting in vivo. CD4+ T cells were purified from spleens of OVA-sensitized and challenged mice by using the Mouse CD4 Cell Positive Isolation Kit and incubated with anti-CD3 mAb (1 μg/ml) in the presence of various concentrations of GA (10 and 100 μg/ml), U0126 (10 μmol/L) or SB203580(10 μmol/L). After 72 h of incubation, the relative protein expression of ERK1/2 and p38 MAPK of CD4 + T cells were detected by Western blotting in vitro.
The asthmatic mice induced infiltration of inflammatory cells around airways and blood vessels, airway goblet cell hyperplasia and mucus production. Administration of GA at a dose of 100 mg/kg, U0126 or SB203580 significantly reduced the infiltration of inflammatory cells in the peribronchial areas and goblet cell hyperplasia compared with the asthmatic mice. The protein expressions of p-ERK1/2 were lower in GA at a dose of 100 mg/kg (0.090±0.022) and U0126 group (0.072±0.017) than those in asthmatic group (0.143±0.022) (all P<0.05). The protein expressions of p-p38 MAPK were lower in GA at a dose of 100 mg/kg (0.072±0.019) and SB203580 group (0.061±0.015) than those in asthmatic group (0.121±0.022) (allP<0.05) by immunohistochemistry. Compared with asthmatic group (0.783±0.133, 0.649±0.095), the protein expressions of p-ERK1/2 and p-p38 MAPK in GA at a high dose group (0.385±0.186, 0.275±0.089) and in U0126 group (0.117±0.051) or in SB203580 group (0.108±0.043) were decreased by Western blotting (allP<0.05). The expressions of p-ERK1/2 in CD4+ T cells after 72 h incubation were lower in 100 μg/ml concentrations of GA (0.579±0.184) and group U0126 (0.249±0.082) and the expressions of p-p38 MAPK were much lower in 100 μg/ml concentrations of GA (0.445±0.081) and group SB203580 (0.249±0.082) compared with those in group CD3 (1.028±0.147, 0.902±0.107) (all P<0.05).
ERK1/2 and p38 MAPK signaling pathways are activated in asthmatic mice and GA may negative regulate this activation.
Two cases of Takayasu arteritis complicated with ulcerative colitis
Patient 1Male, 16 years old, was admitted to the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University on August 10, 2016 due to "intermittent fever and cough for more than 6 months". The patient developed fever on February 2, 2016, with a maximum body temperature of 40 ℃, accompanied by muscle pain in the chest, back and calf, cough and cough a small amount of yellow phlegm, and was admitted to the local hospital. Blood test routine: white blood cells 27.6×109/L, neutrophil ratio 77.8%, neutrophil number 21.34×109/L; Bone marrow cytology: no abnormalities. "Azithromycin, ribavirin, levofloxacin" was given, but the effect was poor. Past history: The stool has not formed in the past 5 years. In the past 1 year, bilateral chewing muscles have repeated pain, inability to chew hard food, and intermittent dizziness. Physical examination after admission: body temperature 38.5 ℃, blood pressure: 123/67 mmHg on the right side (1 mmHg =0.133 kPa), 117/62 mmHg on the left side, and blow-like vascular murmur could be heard in bilateral neck vessels. Blood routine: white blood cells 20.2×109/L, hemoglobin 105 g/L; Erythrocyte sedimentation rate 29 mm/1 h, CRP 69.47 mg/L; Ultrasound: Intima-media thickening of bilateral common carotid arteries, approximately 3.3 mm in the left total neck thicker area and 1.7 mm in the right total neck thicker area, Takayasu arteritis (TA) considered; PET-CT: Diffuse metabolism of the colon is active, and multiple enlarged lymph nodes around the intestine and retroperitoneum are metabolically active. Inflammatory lesions are more considered, and endoscopy is recommended. Colonoscopy: ileocecal, ascending colon, hepatic flexure of colon, transverse colon, splenic flexure of colon, descending colon, sigmoid colon, and rectal mucosa were granular, with unclear vascular texture, diffuse small ulcers, covered with purulent coating, scattered erosion, polyp formation, diagnosis: ulcerative colitis (UC). Descending colon pathology: chronic active inflammation of the mucosa with lymphoid tissue hyperplasia. Diagnosis: TA, UC. He was given methylprednisolone, sulfasalazine enteric-coated tablets and other drugs, and his condition was stable after regular follow-up in out-of-hospital clinic.
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