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Objective @#To construct hepatocyte-specific silence information regulator 3 ( Sirt3 ) gene knockout (Sirt3Δhep ) mice by Cre-loxP technique , and to provide an important animal model for further studying the biological function of the hepatocyte Sirt3 gene in diseases . @*Methods @#LoxP-labeled Sirt3flox/flox mice were mated with Alb-Cre homozygous (Alb-Cre + / + ) mice , and the F1 generation Sirt3flox/ - /Alb-Cre + / - mice were then mated with Sirt3flox/flox mice , and the F2 genotype of Sirt3flox/flox/Alb-Cre + / - mice were the Sirt3Δhep mice constructed in this ex- periment. Sirt3flox/flox/Alb-Cre - / - (Sirt3flox/flox ) mice were the control mice . Mouse tail genome DNA was extracted and PCR was used to identify the genotypes of the offspring mice . Immunofluorescence was used to detect Sirt3 ex- pression in mouse hepatocytes . Primary hepatocytes and tissue proteins of Sirt3Δhep mice were extracted , and the ex- pression of Sirt3 in mouse hepatocytes and other tissues was verified by Western blot. HE staining was used to ob- serve mice ′s liver , heart , spleen , and lung tissue structure . @*Results @#Sirt3Δhep mice were successfully identified .Immunofluorescence and Western blot results demonstrated a significant decrease in the expression of Sirt3 in the hepatocytes of these mice compared to the control group ( P < 0. 01) . At the same time , there was no significant difference in the expression of Sirt3 in the heart , spleen , kidney , and lung tissues of Sirt3Δhep mice compared with the control group (P > 0. 05) . The results of HE staining showed that the histological characteristics of the liver , heart , spleen , lungs , kidneys , and other major organs of Sirt3Δhep mice were not significantly different from those of the control group mice . @*Conclusion @#Hepatocyte-specific Sirt3 gene knockout mice are successfully constructed , which provides an animal model to explore further the role and molecular mechanism of the hepatocyte Sirt3 gene in diseases .
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Objective:To investigate the protective effect of naringenin on acute lung injury related with sepsis; To discuss its possible mechanism.Methods:Totally 30 male SD rats were randomly divided into sham-operation group, model group, naringin low-, medium- and high-dosage groups, with 6 rats in each group. The sepsis-related acute lung injury model was established by cecal ligation and puncture in all groups except the sham-operation group. After modeling, naringin low-, medium- and high-dosage groups were given naringin 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively for gavage, while the sham-operation group and the model group were given the same volume of distilled water by gavage, once a day, for 2 days. Pathological changes in lung tissue were observed using HE staining. The levels of 1L-1, IL-6 and IL-18 in bronchoalveolar lavage fluid (BALF) were measured by ELISA; the expression of TNF-α in lung tissue was detected by immunofluorescence histopathology; the expressions of TGF-β1, TGF-βR1 and Smad2 were detected by Western Blot. An agonist group and a naringin plus agonist group were set up, with 6 mice in each group, and the expressions of TGF-β1 and Smad2 protein in the lung tissue of each group were detected by immunohistochemical staining to verify the effect of naringin on the expressions of TGF-β1 and Smad2 protein.Results:Compared with the model group, the pathological injury of lung tissue in naringin groups were obviously alleviated, and the levels of IL-1β, IL-6 and IL-18 in BALF decreased ( P<0.01), the protein expressions of TNF-α, TGF-β1, TGF-βR1 and Smad2 in lung tissue decreased ( P<0.01 or P<0.05). Further verification found that the expressions of TGF-β1 and Smad2 in the agonist group increased ( P<0.01), while the expressions of TGF-β1 and Smad2 in the naringin agonist group decreased ( P<0.01). Conclusion:Naringin can reduce the inflammatory response in the lung of the rats to protect against sepsis-related acute lung injury, and its protective effect could be related to the inhibition of the TGF-β1/Smad2 signaling pathway.
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Guidelines for the prevention and treatment of chronic hepatitis B （2022 edition） expanded the indications for antiviral therapy in patients with chronic hepatitis B. The guidelines recommend to initiate antiviral therapy for patients with chronic HBV infection who have a normal alanine aminotransferase （ALT） level， positive HBV DNA， and an age of >30 years. However， for pregnant women aged >30 years， no consensus has been reached on whether to start antiviral therapy immediately. Some experts believe that pregnant women with a normal ALT level are mostly in the immune-tolerant phase， and antiviral therapy tends to have an unsatisfactory therapeutic effect； in addition， medication during pregnancy may affect the safety of mothers and fetuses. Therefore， it is not recommended to start antiviral therapy immediately in early pregnancy even if the pregnant women are aged >30 years. Other experts believe that immune changes of the body during pregnancy may be a special period for HBV immune clearance， and if the patients are aged >30 years， antiviral therapy should be initiated immediately even if the patient has a normal ALT level； pregnant women may get better virologic and even serological response. With a focus on the above issues， this article elaborates on the purpose， treatment timing， and drug withdrawal timing of antiviral therapy during pregnancy.
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Deep brain electrical stimulation is one of the emerging therapeutic approaches for treatment-resistant depressive disorders.This article outlines a variety of potential targets for deep brain electrical stimulation in the treatment of treatment-resistant depressive disorders and summarizes the results of relevant clinical studies.These targets include the subgenual cingulate gyrus,nucleus accumbens,ventral capsule and ventral striatum area,medial forebrain bundle,and lateral habenula,among other regions.Based on these studies,the article integrates relevant basic research and further discusses the possible mechanisms through which deep brain stimulation may exert therapeutic effects,including synaptic plasticity,neurophysiology,neural circuits,and neurotransmitters.The article also assesses and prospects the further application potential of deep brain electrical stimulation.The authors believe that the multi-target stimulation combining existing clinical research results and neurobiological mechanisms could be a crucial development direction to enhance the treatment of treatment-resistant depressive disorders using deep brain electrical stimulation.
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Objective:To explore the characteristics of the association between the triglyceride glucose (TyG) index and nonfatal cardio-cerebrovascular disease risk in a community population.Method:This was a prospective cohort study. From December 2011 to April 2012, the first investigation was conducted among subjects with more than 40-year old who were from Shijingshan district and Pingguoyuan community in Beijing. The second investigation was conducted from April to October 2015. All the subjects were divided into three groups according to the tertile of the TyG index at baseline. The multivariate Cox proportional risk regression model was established to explore the correlation between the TyG index and nonfatal cardio-cerebrovascular disease risk and the Kaplan-Meier survival curve of the TyG index group was drawn. Subgroup analyses were performed according to age, gender, body mass index, type 2 diabetes mellitus (T2DM), hypertension, and hyperlipidemia to determine the correlation characteristics between the TyG index and nonfatal cardio-cerebrovascular disease among subgroups.Results:A total of 9 577 subjects were finally included to analyze. The mean follow-up time of this study was (34.14±3.84) months. During the follow-up, 363 subjects (3.8%) occurred nonfatal cardio-cerebrovascular disease. The multivariate Cox regression analysis results showed that the hazard ratio ( HR) of nonfatal cardio-cerebrovascular disease in the high TyG index group was 1.54 (95% CI 1.19-1.98), 1.60 (95% CI 1.23-2.10), and 1.57 (95% CI 1.20-2.05) in the three models, compared with the low TyG index group. The Kaplan-Meier analysis showed that the risk of nonfatal cardio-cerebrovascular disease increased from the low-TyG index group to the high-TyG index group ( P=0.015). In the six subgroups analysis, only gender was shown to have a significant interaction effect with the TyG index and nonfatal cardio-cerebrovascular disease risk. In the female population, the risk of nonfatal cardio-cerebrovascular disease is significantly increased with the increase in the TyG index level ( P<0.001). Conclusions:A high TyG index is independently related to the increased risk of nonfatal cardio-cerebrovascular disease in the Beijing community population. Gender has a significant interaction with the TyG index and nonfatal cardio-cerebrovascular disease risk. Therefore, the TyG index may be a useful marker to predict the nonfatal cardio-cerebrovascular disease risk of a community population.
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Objective:To investigate the protective function and mechanism of β-hydroxybutyrate (β-HOB) on cisplatin (CP)-induced nephrotoxicity.Methods:C57BL/6 male mice aged 10 weeks were randomly divided into the following three groups: control group (no special treatment), β- HOB+CP group (mice received intraperitoneal injection of 20 mmol/kg β-HOB for 10 days), CP group (received intraperitoneal injection of normal saline for 10 days). CP group and β-HOB+CP group were given once cisplatin (20 mg/kg) intraperitoneal injection on the 8th day in the experiment. On the 10th day, all the mice were sacrificed. Renal pathology was evaluated by HE staining; blood samples were collected for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement; immunohistochemistry staining was performed to detect the protein level of Caspase3, Cleaved-caspase3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in renal tissues; Western blotting was used to detect the relative expression levels of p-MAPK/MAPK and p-NF-κB/NF-κB. In vitro experiment, HK-2 cells were set into three groups: control group, CP group, β-HOB+CP group, and β-HOB+CP+Sappanone A (Sap, MAPK-p38 activator) group. The expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 were tested by cell immunofluorescence. The cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry. DNA damage was detected by TUNEL staining. Results:In vivo experiments, the renal pathological injury score, BUN and Scr in CP group were significantly higher than those in control group (all P<0.05), while renal pathological injury score, BUN and Scr in β-HOB+CP group were lower than those in CP group (all P<0.05). The protein expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 in CP group were higher than those in control group, while these indexes in β-HOB+CP group were lower than those in CP group (all P<0.05). In vitro experiments, compared with CP group, the MMP was higher in β-HOB+CP group; the ratio of cell apoptosis, the expression of Caspase3, Cleaved-caspase3, p-MAPK and p-NF-κB, and the number of TUNEL staining positive cells were significantly lower (all P<0.05). Compared with β-HOB+CP group, the MMP in β-HOB+CP+Sap group was lower; the ratio of cell apoptosis, the expression of Caspase3 and Cleaved-caspase3, and the number of TUNEL staining positive cells were significantly higher (all P<0.05). Conclusions:β-HOB can alleviate the acute renal injury induced by cisplatin, which may be related to the reduction of apoptosis and inhibition of MAPK/NF-κB pathway.
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BACKGROUND@#The hemoglobin glycation index (HGI) was developed to quantify glucose metabolism and individual differences and proved to be a robust measure of individual glycosylated hemoglobin (HbA1c) bias. Here, we aimed to explore the relationship between different HGIs and the risk of 5-year major adverse cardiovascular events (MACEs) by performing a large multicenter cohort study in China.@*METHODS@#A total of 9791 subjects from the Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study (the REACTION study) were divided into five subgroups (Q1-Q5) with the HGI quantiles (≤5th, >5th and ≤33.3th, >33.3th and ≤66.7th, >66.7th and ≤95th, and >95th percentile). A multivariate logistic regression model constructed by the restricted cubic spline method was used to evaluate the relationship between the HGI and the 5-year MACE risk. Subgroup analysis between the HGI and covariates were explored to detect differences among the five subgroups.@*RESULTS@#The total 5-year MACE rate in the nationwide cohort was 6.87% (673/9791). Restricted cubic spline analysis suggested a U-shaped correlation between the HGI values and MACE risk after adjustment for cardiovascular risk factors ( χ2 = 29.5, P <0.001). After adjustment for potential confounders, subjects with HGIs ≤-0.75 or >0.82 showed odds ratios (ORs) for MACE of 1.471 (95% confidence interval [CI], 1.027-2.069) and 2.222 (95% CI, 1.641-3.026) compared to subjects with HGIs of >-0.75 and ≤-0.20. In the subgroup with non-coronary heart disease, the risk of MACE was significantly higher in subjects with HGIs ≤-0.75 (OR, 1.540 [1.039-2.234]; P = 0.027) and >0.82 (OR, 2.022 [1.392-2.890]; P <0.001) compared to those with HGIs of ≤-0.75 or >0.82 after adjustment for potential confounders.@*CONCLUSIONS@#We found a U-shaped correlation between the HGI values and the risk of 5-year MACE. Both low and high HGIs were associated with an increased risk of MACE. Therefore, the HGI may predict the 5-year MACE risk.
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Humains , Études de cohortes , Études longitudinales , Diabète de type 2/diagnostic , Réaction de Maillard , Hémoglobine glyquée , Maladies cardiovasculairesRésumé
To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61;95% confidence interval [95% CI], −2.44 to −0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.
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OBJECTIVE To establish the fingerprint of Zhuang medicine Jinmu granules and carry out chemometric analysis ， and determine the contents of three components . METHODS High performance liquid chromatography （HPLC） method was adopted. Using rutin as the reference ，HPLC fingerprints of 10 batches of Jinmu granules were drawn and similarity evaluation was performed by Similarity Evaluation of Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）；the common peak was determined by comparing with mixed control ；SPSS 21.0 software was used for cluster analysis ，and SIMCA 14.1 software was used for principal component analysis and orthogonal partial least squares-discriminant analysis. The differential components affecting the quality of Jinmu granules were screened by taking the variable importance in projection （VIP）value ＞1 as the standard ；the HPLC method was used to determine the contents of astilbin ，polydatin and berberine hydrochloride in Jinmu granules. RESULTS There were 22 common peaks in 10 batches of Jinmu granules ，and the similarities were 0.962-0.997；five common peaks were identified ，namely gallic acid （peak 2），polydatin（peak 9），rutin（peak 11），astilbin（peak 13）and kaempferol （peak 20）. The results of cluster analysis showed that 10 batches of Jinmu granules could be clustered into 3 categories：S1 and S 3-S4 were grouped into one category ；S5-S6 and S 9 were grouped into one category ；S2，S7-S8 and S 10 were grouped into one category. The results of principal component analysis showed that the parameter of model interpretation was 0.951 and that of prediction ability was 0.723. The classification results were basically consistent with cluster analysis. The classifica tion results of orthogonal partial least squares- com discriminant analysis were also ba sically consistent with clus- ter analysis. The common peaks with VIP value ＞1 in the order were peak 7＞peak 11（rutin）＞peak 17＞peak 13（astilbin）＞ peak 3＞peak 8＞peak 6＞peak 16 respectively. The linear ranges of astilbin ，polydatin and berberine hydrochloride were 0.012 6- 1.225 0，0.010 8-1.052 5 and 0.020 0-1.562 5 mg/mL，respectively（all R 2＝0.999 9）. RSDs of precision ，stability（24 h）and repeatability tests were all less than 3％. The average recoveries were 99.48％（RSD＝2.67％，n＝9），98.57％（RSD＝1.77％，n＝ 9）and 100.84％（RSD＝2.49％，n＝9）. The contents were 1.221 0-7.011 6，2.251 1-4.462 9，1.252 4-3.328 7 mg/g，respectively. CONCLUSIONS Established fingerprint and the method of content determination are accurate ，stable and simple. Combined with chemometric analysis ，it can be used for the quality control and evaluation of Zhuang medicine Jinmu granules.
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Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.
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Objective:To explore the learning guidance model and its influencing factors of undergraduates in medical schools.Methods:Based on the developmental learning guidance theory, 1 117 undergraduates from two undergraduate medical universities were selected as the research objects, through questionnaire surveys to collect their knowledge learning, curriculum learning and other core variables, and balanced guidance, compound guidance and other outcome variables, using Smart PLS 3.0 to test the validity of the samples.Results:There were statistical significance in the path relationship affecting the core variables and the outcome variables of the learning guidance model, P<0.05, indicating that the influencing factors of the learning guidance model had a significantly positive effect on the learning guidance model construction. Conclusion:Constructing a "balanced-compound-special" learning guidance model suitable for undergraduates' learning activities in medical universities provides a reference for the application and promotion of learning guidance model in medical undergraduate stage.
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Objective:To explore the influence of symptom group of stroke patients with exercise disorder on acute stress disorder.Methods:Patients with stroke and motor impairment hospitalized in the Department of Neurology and surgery of North China University of technology from October 2018 to August 2019 were selected as the research objects.The general information of patients, brain injury subscale (BIS) and Stanford acute stress reaction questionnaire (SARSQ) were investigated by questionnaire.Results:A total of 324 patients with stroke and motor disorders were investigated.The demographic characteristics of education, age, degree of motor function, number of combined dysfunction and Activity Of Daily Living Scale(ADL) grade had effects on acute stress disorder, and the differences were statistically significant( P<0.05). The score of acute stress disorder in stroke patients with motor disorders was (99.60±13.69 ) points.From the highest to the lowest symptom group, the scores were obsessive symptom (11.35±2.71), depression (7.44±1.86), hostility (7.23±2.26), somatization (3.69±1.42) and psychosis (2.81±1.09). The results of correlation analysis showed that somatization, depression, obsessiveness, hostility and psychosis were positively correlated with the total score of acute stress disorder and the scores of each dimension ( r=0.164, 0.355, 0.329, 0.298, 0.279, all P<0.05), the symptoms were also positively correlated with all the dimensions of acute stress disorder(all P<0.05). Multiple linear regression analysis showed that age(Regression coefficient=7.682, 95% CI: 4.930-10.435, P<0.001), the number of combined dysfunction(Regression coefficient=3.937, 95% CI: 0.268-7.605, P=0.036), depression(Regression coefficient=1.662, 95% CI: 0.727-2.597, P=0.001) had influence on ASD of stroke patients. Conclusion:The level of acute stress disorder in stroke patients with motor impairment is on the high side, and the characteristics of symptom group are obvious, which has a positive correlation with acute stress disorder.Medical staff should pay attention to the characteristics of symptom group and acute stress reaction level of stroke patients with motor impairment, so as to provide targeted intervention strategies to avoid disease recurrence and improve the quality of life.
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Objective@#To clarify the importance and practical significance of the standardized rate in primary healthcare work by comparing the differences in the prevalence of myopia in districts in Beijing before and after standardization.@*Methods@#This study recruited a total of 41 029 students from 107 primary and secondary schools and 35 kindergartens from the 16 districts of Beijing municipality. All participants underwent distance vision and refractive testing. The presence of myopia was defined as naked eye vision of <5.0 and non-ciliary muscle paralysis under computer optometry with a spherical equivalent objective refractive error of <-0.50 diopters (<-0.50 D). The student composition outlined in the 2018-2019 Beijing Education Development Statistics Summary was used as a standard group to standardize the prevalence of myopia in students from various districts of Beijing. The difference in the pre-and post-standardization rates was used to compare the change in myopia in each district before and after standardization.@*Results@#In 2018, the prevalence of myopia in students from Beijing was 57.3%. Stratified by school period, the prevalence of myopia in preschool, primary school, junior high school, ordinary high school, and vocational high school students was 12.1%, 38.4%, 77.2%, 88.3%, and 73.1%, respectively. Although the prevalence of myopia in Daxing District was the highest both before and after standardization, the difference in the prevalence rate was 13.8 percentage points. The prevalence of myopia in Miyun District was the lowest before standardization. However, after standardization, the prevalence of myopia was lowest in Huairou District.@*Conclusion@#The prevalence of myopia among Beijing students is generally high. Before and after standardization, the prevalence of myopia in different districts was quite different. The results show that, in practice, the standardized prevalence can reveal the true epidemiological characteristics of specific disease.
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Traditional endocrine drugs, such as bicalutamide, are the first choice for neoadjuvant therapy of prostate cancer. There are few reports on the use of new endocrine drugs in neoadjuvant therapy in China. The patient, male, 63 years old. He was admitted to the hospital for the finding of prostate space occupying. Blood PSA 53.50 ng / ml. Prostate MRI suggested that the prostate lesion broke through the left capsule, the left seminal vesicle gland was invaded, and the bladder wall was invaded. Bone scan suggested that: the left 8th posterior costal branch radioactivity was limited and increased. Prostate adenocarcinoma was diagnosed by puncture, Gleason score 4 + 4 = 8 points, and stage T 4bN 1M 1. The patient was treated with goserelin combined with enzalutamide for 3 months, and PSMA-PET CT: prostate size was normal, no significant 68Ga PSMA uptake was increased, no abnormally high Ga PSMA uptake in bones. The patient was treated with enzalutamide combined with ADT as neoadjuvant endocrine therapy, winning surgical conditions for the patient to undergo surgical resection.
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Objective To investigate the neuroprotective effect of Benztropine on retinal ganglion cells (RGCs) death and optic nerve injury in rats model of non-arteritis anterior ischemic optic neuropathy (rNAION).Methods A total of 25 Sprague-Dawley rats were randomly divided into Benztropine treatment group (n=13)and PBS control group (n=12).The right eye was set as the experimental eye.rNAION model was established by using rose Bengal combined with laser photodynamic method.The rats in the Benztropine treatment group were received intraperitoneal injection with Benztropine 10 mg/kg (0.2 ml) daily for 3 weeks,while the rats in the PBS control group were received intraperitoneal injection with an equal volume of PBS.At 1,3 and 7 days after modeling,the retinal and optic disc conditions of the rats were observed by direct ophthalmoscopy.Retrograde labeling,fluorescence microscopy and transmission electron microscopy were used to observe the survival of RGCs and the damage of the optic nerve myelin and axon at 4 weeks after modeling.The RGCs density and survival rate of the two groups were compared by One-Way Anova.Results At 1 and 3 days after modeling,the optic disc edema was observed in the rats of rNAION model group.At 7 days after modeling,the optic disc edema decreased and the boundary was blurred compared with 3 days after modeling.After 4 weeks,the RGCs density in the PBS group was 308± 194/mm2 and the survival rate was 13.7％.The density of RGCs in the Benztropine group was 1173+868/mm2 and the survival rate was 47.6％.The differences of RGCs density and survival rate were significant between the two groups (F=7.552,8.184;P=0.015,0.012).Myelin disintegration,axon degeneration,onion-like body and gliosis were observed in the optic nerve sections of rNIAON in the PBS group,while the damage ofaxon and myelin structure in the Benztropine group was significantly less than that in the PBS group.Conclusions Benztropine group showed higher RGC survival rate,less damage ofaxon and myelin structure on rNAION model.This study explored the potential neuroprotective effect of Benztropine.
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Objective To analyze the characteristics of the primary headache due to cervicocerebral artery dissection (CAD).Methods A total of 146 consecutive patients with CAD in the First Affiliated Hospital of Zhengzhou University from 2010 to 2017 were observed.There were 20 cases who complained of primary headache,of which the characteristics of pain were analyzed according to their clinical features that were collected face to face through questionnaire.According to whether complicated by primary headache,the 146 patients were classified into two groups:20 cases (13.7％) in the primary headache group,and 126 cases (86.3％) in the non-primary headache group.Results Patients in the primary headache group had a lower prevalence of transient ischemic attack or cerebral infarction compared with the non-primary headache group (30.0％ (6/20) vs 77.0％ (97/126),x2=18.338,P＜0.01).CAD patients in the primary headache group were more likely involved in posterior circulation compared with the non-primary headache group (85.0％ (7/20) vs 55.6％ (70/126),x2=6.214,P=0.013).Of the 20 patients with primary headache,40.0％ (8/20) had continuous headache and 60.0％ (12/20) had intermittent headache;70.0％ (14/20) presented with severe headache,25.0％ (5/20) with moderate headache and 5.0％ (1/20) with mild headache;For the nature of pain,60.0％ (12/20) was similar to migraine;11/17 of patients with posterior circulation dissection showed occipital pain.Conclusions The primary headache caused by CAD is a severe pain occurring suddenly,and different from those of previous experiences.The nature of headache is often similar to migraine,which can be continuous or intermittent.In addition,compared with anterior circulation,patients with posterior circulation dissection often have headache as the initial symptom.
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Objective To investigate the role of mast cells in Staphylococcus aureus enterotoxin B (SEB)-induced atopic dermatitis (AD)-like skin inflammation in BALB/c mice.Methods A total of 24 BALB/c mice were randomly and equally divided into 4 groups to be topically treated with ovalbumin (OVA group),SEB (SEB group),OVA + SEB (OVA + SEB group) and sodium chloride physiological solution (control group) respectively,so as to establish mouse models of epicutaneously induced AD-like skin inflammation.The AD-like skin lesions were evaluated by clinical observation and eczema area and severity index (EASI).Biopsy specimens were obtained from lesional skin of mice and then subjected to toluidine blue staining and immunohistochemical staining to count the mast cells,observe the morphology and distribution of mast cells,and calculate the percentage of degranulated mast cells.Results After 7-week treatment,the OVA group,SEB group and OVA + SEB group all showed severer local skin inflammation,higher EASI scores and denser infiltration of inflammatory cells compared with the control group.Moreover,the OVA + SEB group showed significantly severer local skin inflammation,skin lesions and degree of infiltration of inflammatory cells compared with the OVA group and SEB group (all P ＜ 0.05).The number of mast cells in the dermis of AD-like skin lesions per high-power field (× 400) was significantly higher in the OVA group (median [quartile range]:10.625 [3.675]),SEB group (11.000 [4.163]) and OVA + SEB group (13.875 [8.813]) than that in the control group (5.925 [2.088],all P ＜ 0.05).The SEB group (71.083％ ± 14.519％) and OVA + SEB group (58.767％ ±.16.978％) both showed significantly higher percentage of degranulated mast cells compared with the OVA group (24.050％ ± 11.161％,both P ＜ 0.05) and control group (23.617％ ± 8.132％,both P ＜ 0.05).Bivariate correlation analysis showed that the number of mast cells in the skin lesions was positively linearly correlated with the EASI scores (P ＜ 0.05).Conclusions Epicutaneous application of SEB can induce AD-like skin lesions in mice,and can exacerbate the severity of OVA-induced AD-like skin lesions.Mast cell proliferation,activation/degranulation and tryptase release may participate in the inflammation.
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Objective To evaluate the efficacy and safety of Qingpeng ointment for the treatment of localized eczema in children.Methods A multicenter,randomized,open-labeled,tacrolimus 0.03％ ointment-controlled clinical trial was conducted.A total of 442 children with localized eczema were enrolled into this study,and divided into 2 groups to topically apply Qingpeng ointment (Qingpeng group) and tacrolimus 0.03％ ointment (tacrolimus group) respectively twice a day for 2 weeks.The children were followed up before the treatment and 1,2 weeks after the treatment,and the efficacy and safety were evaluated at the same time.Results Clinical data from 426 children were included in the efficacy analysis.At 1,2 weeks after the treatment,there were no significant differences in the response rate between the Qingpeng group and tacrolimus group (1 week after the treatment:78.92％ vs.81.77％,x2 =0.545,P =0.460;2 weeks after the treatment:98.65％ vs.97.54％,x2 =0.721,P =0.396).However,the pruritus scores at 1,2 weeks after the treatment were both significantly lower in the Qingpeng group than in the tacrolimus group (1 week:F =14.001,P =0.000;2 weeks:F =11.252,P =0.001).At 1 week after the treatment,the incidence rate of adverse reactions was significantly lower in the Qingpeng group than in the tacrolimus group (P ＜ 0.05).Mild itching,burning sensation and other local irritant sensations were the most common adverse reactions.Conclusion Qingpeng ointment is safe and effective for the treatment of localized eczema in children with good tolerability.
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Objective To investigate the role of Staphylococcus aureus enterotoxin B (SEB) in non-IgE mediated activation of mast cells (MCs) by in vitro co-culture of laboratory of allergic disease 2 (LAD2) cells and SEB.Methods The LAD2 cells were incubated with SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,A23187 positive control and negative control separately for 30 minutes.Then,effects of SEB on the morphology of MCs were observed by using a light microscope,and culture supernatants of the above incubation systems were collected.The concentration of tryptase released from MCs was analyzed by enzymatic activity assay,and the level of histamine was detected by enzyme-linked immunosorbent assay (ELISA).Results After 30-minute co-culture of LAD2 cells and SEB,MCs showed larger size,obscure boundaries,increased number of protuberances on the cell surface and decreased refractivity,with a radial burr fin-like appearance.After 30-minute co-culture of LAD2 cells and SEB at different concentrations of 0.01,0.1,1,10 and 100 μg/ml,the concentrations of tryptase in the culture supematants were 4.116 ± 0.651,5.344 ± 0.874,3.806 ± 0.459,1.309 ± 0.247,0.310 ± 0.199 ng/ml respectively.Additionally,the tryptase levels were significantly higher in the 0.01-,0.1-,1-μg/ml SEB groups than in the negative control group(1.538 ± 0.490,all P ＜ 0.05),and gradually decreased along with the increase of SEB concentrations.The histamine levels in the 0.01-,0.1-,1-,10-and 100-μg/ml SEB groups were 242.409 ± 63.915,522.491 ± 73.466,550.926 ± 84.466,334.397 ± 33.640,226.527 ± 5.678 ng/ml respectively.In the 0.01-,0.1-,1-μg/ml SEB groups,the levels of histamine released from MCs were gradually increased along with the increase of SEB concentrations,and were significantly higher than those in the negative control group (146.436 ± 3.100,all P ＜ 0.05).However,with the continued increase of SEB concentrations,the histamine levels gradually decreased.Conclusion SEB can directly activate MCs by a non-IgE mediated mechanism,followed by morphologic changes of MCs and release of tryptase and histamine.
Résumé
Objective To observe the changes in subfoveal choroidal thickness (SFCT) and peripapillary choroidal thickness (pCT) in nonarteritic anterior ischemic optic neuropathy (NAION). Methods Nineteen newly occurred NAION patients were included. The patients were divided into group A (20 affected eyes of 19 patients) and B (18 fellow eyes of 18 patients). Twenty eyes of 20 age, gender, intraocular pressure and axial length-matched healthy volunteers (group C) were enrolled in this study. The differences of age (t=1.58), gender ratios (χ2=0.107), intraocular pressure (t=0.092) and axial length (t=0.148) between 3 groups were not significant (P>0.05). SFCT, pCT were measured at first visit, 1 month and 3 months after treatment using enhanced deep imaging technique of spectral domain optical coherence tomography. The correlation of best corrected visual acuity (BCVA) and the choroidal thickness was investigated. Results At the first visit, the mean SFCT and pCT in group A were significant thicker than group C (t=2.957, 2.844; P=0.006, 0.009). There was no difference of SFCT and pCT between group B and C (t=2.019, 2.024; P=0.053, 0.057). There was no correlation between BCVA and SFCT, pCT (F=0.161, 0.033; P=0.695, 0.859). One month after treatment, SFCT in group A was still thicker than group C (t=2.803, P=0.009); while pCT was decreased in group A when compared to group C, but the difference was not significant (t=1.871, P=0.084). Three months after treatment, the differences of SFCT and pCT were not significant between group A and C (t=1.223, 1.105; P=0.236, 0.282). Conclusions At first visit, SFCT and pCT in NAION eyes showed a significant increase when compared to normal eyes. One month later, pCT in NAION eyes decreased to normal. Three months later, both SFCT and pCT decreased. These findings may suggest that a thickened choroid is a clinical characteristic at acute stage in NAION eyes.