Differential Regulation of Integrin α5 and ß4 in Normal and Psoriatic Epidermal Keratinocytes

Abstract Psoriasis is a chronic skin inflammation, characterized by impaired differentiation, hyperproliferation of keratinocytes involving pro-inflammatory factors interleukin (IL)-13/17A, tumor necrosis factor (TNF)-α, interferon (IFN)-γ. Among the integrin family, α5 is important for blood vessel formation, and ß4 for proliferation, differentiation of keratinocytes. To investigate the expression and regulation of integrin α5 and ß4 in psoriatic keratinocytes. Skin biopsies were obtained from 14 psoriatic patients and 12 normal volunteers. We compared the immunolocalization and regulation of α5 and ß4 between the psoriatic and normal ones, before and after incubation with MEK/ERK pathway inhibitor U0126 by immunohistochemistry and western blot separately. Immunohistochemistry showed psoriatic keratinocytes had higher α5 than normal ones. According to western blot, IL-17A and IL-13 increased normal keratinocytes' α5 and ß4 respectively, but psoriatic keratinocytes were the exact opposite. Incubated with U0126, normal keratinocytes' α5 was enhanced by the 5 cytokines ; while IL-13/17A, IFN-γ suppressed ß4. Psoriatic keratinocytes' α5 was increased by IL-13/17A, decreased by IFN-γ; but ß4 increased by IL-17A, IFN-γ. IL-13/17A, TNF-α, IFN-γ regulate α5 and ß4 through ERK pathway whether normal or psoriasis. The normal and psoriatic keratinocytes respond to the same cytokines differently

A five-year follow-up report on lung imaging and exercise endurance of a patient with paraquat poisoning / 中华劳动卫生职业病杂志

A patient with paraquat poisoning was followed up for five years, and it was showed that the interstitial lesion areas in chest CT of this patient gradually decreased after acute period of the poisoning and no significant changes were found six months later. After that the density of the lesions gradually reduced, while the cystic air cavities slowly increased. In addition, the patient's exercise endurance gradually improved over time, and the lung function was close to the normal level five years after poisoning. The follow-up report helps clinicians to have a deeper understanding of the long-term outcome of paraquat poisoning.

Clinical features and classification of 180 patients with morphea / 中华皮肤科杂志

Objective:To determine classification and clinical features of morphea.Methods:A retrospective analysis was conducted on epidemiological information about clinical manifestations of and laboratory data from 180 patients with morphea, who visited Zhongshan Hospital, Fudan University from January 2010 to July 2021. Two-independent-sample t test was used to compare the age at onset between genders, and chi-square test to analyze differences in clinical characteristics between different genders and subtypes. Results:Among the 180 patients, 123 were females and 57 were males, with a male-to-female ratio of 1∶2.16. The age at onset of morphea was 28.69 ± 17.97 years for female patients, and 29.90 ± 20.67 years for male patients. Among them, linear morphea was the most common type in this study (68 cases, 37.78%), followed by plaque morphea (63 cases, 35.00%), mixed morphea (28 cases, 15.56%) and deep morphea (21 cases, 11.67%). The disease occurred in all age groups, but the age at onset significantly varied among different clinical subtypes ( F = 5.95, P < 0.001). No significant difference was observed in the age at onset or proportion of clinical subtypes between genders ( F = 0.15, P = 0.696; χ2 =2.88, P = 0.410). Atrophoderma of Pasini and Pierini (APP) was very common (62 cases, 34.44%) in the 180 patients, which mainly manifested as plaques or linear lesions, and 26 out of 45 patients with plaque APP and 11 out of 17 with linear APP were both accompanied by other subtypes of morphea. Among the 75 patients tested for autoantibody profiles, 34 (45.33%) presented with positive results. More diverse types of autoantibodies were found in female patients compared with male patients, and antinuclear antibodies, anti-SSA and anti-SSB antibodies were the most common types. There were various types of comorbidities in female patients, but lichen sclerosus et atrophicus and vitiligo were the most common comorbidities in both genders. Conclusion:High incidence and frequent co-occurrence with other subtypes of APP may be the characteristics of Chinese patients with morphea, and it is recommended to classify morphea into plaque, linear, deep and mixed subtypes.

Xuebijing Injection Ameliorates H / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H@*METHODS@#Sprague-Dawley rats were exposed to H@*RESULTS@#The morphological investigation showed that XBJ attenuated H@*CONCLUSIONS@#XBJ ameliorated H

Protective effect of extracorporeal membrane pulmonary oxygenation combined with cardiopulmonary resuscitation on post-resuscitation lung injury / 世界急诊医学杂志（英文）

@#BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.

Seborrheic dermatitis-distributed dermatomyositis: a special type of dermatomyositis / 中华皮肤科杂志

Seborrheic dermatitis-distributed dermatomyositis, a special type of dermatomyositis, is characterized by facial seborrheic dermatitis-distributed rashes, usually accompanied by Gottron papules, inverse Gottron papules, mechanic′s hands and skin ulcers, seldom accompanied by muscle involvement. Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients with seborrheic dermatitis-distributed dermatomyositis are prone to interstitial lung disease/rapidly progressive interstitial lung disease. Early diagnosis of seborrheic dermatitis-distributed dermatomyositis can be made through the combination of rashes and antibody detection, and early and active combined treatment with glucocorticoids and immunosuppressors can improve the survival rate of patients.

The effect of hematoma puncture drainage before decompressive craniectomy on the prognosis of hypertensive intracerebral hemorrhage with cerebral hernia at a high altitude / 中华创伤杂志(英文版)

PURPOSE@#Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone.@*METHODS@#From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests.@*RESULTS@#A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ@*CONCLUSION@#PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.

Identify pathogenic mutations of <i>CYP4V2</i> gene in Bietti crystalline corneoretinal dystrophy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To identify pathogenic mutations of <i>CYP4V2</i> gene in two Chinese families with Bietti crystalline corneoretinal dystrophy(BCD)by Sanger sequencing. <p>METHODS: The relevant clinical examination of BCD patients were collected. Peripheral blood of patients and their family members was collected. Then DNA was extracted from peripheral blood, and Sanger sequencing was used to identify mutation sites.<p>RESULTS: Two probands of BCD from different families were collected. All the probands showed progressive decrease of visual acuity and typical crystal-like material deposition could be seen in the fundus. Sanger sequencing showed that proband 1 and her brother and sister all had homozygous mutation of c.802-8_810del17insGC in <i>CYP4V2</i> gene. On the other hand, proband 2 had a compound heterozygous mutation of c.219T>A(p.F73L)and c.802-8_810del17insGC in <i>CYP4V2</i> gene. <p>CONCLUSION: The most common mutation was c.802-8_810del17insGC in Chinese BCD patients. The homozygous c.802-8_810del17insGC mutation was the cause of BCD in the proband 1 family. On the other hand, proband 2 had c.802-8_810del17insGC heterozygous mutation and c. 219T>A(p.F73L)heterozygous missence mutation, all of which affected the normal coding of <i>CYP4V2</i> gene and led to disease.

Use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective:To study the use of three-dimensional computer reconstruction in diagnosis and treatment of hilar cholangiocarcinoma.Methods:A retrospective analysis of clinical data was conducted on patients with hilar cholangiocarcinoma admitted to the Department of General Surgery, the First Affiliated Hospital of the University of Science and Technology of China from January 1, 2017 to July 31, 2019. The classification of hilar cholangiocarcinoma, vascular invasion and surgical resectability were determined by preoperative three-dimensional reconstruction. These data were then compared with the findings obtained during operations, by comparing with the three-dimensional reconstruction technology findings in classification of hilar cholangiocarcinoma, vascular invasion, and hilar extent of biliary and vasculature involvement.Results:Of 65 patients included in this study, there were 35 males and 30 females, with an age of (60.35±10.70) years. After operation, these 65 patients were classified into type I ( n=7), type II ( n=4), type III ( n=14), and type IV ( n=40) using the Bismuth classification. The accuracy rates of preoperative three-dimensional reconstruction for hilar cholangiocarcinoma classification, portal vein invasion, hepatic artery invasion, and diagnosis of hilar cholangiocarcinoma vasculature involvement were 90.7% (59/65), 90.7% (59/65), 86.1% (56/65) and 80.0% (52/65) respectively. Conclusions:The three-dimensional computer reconstruction technology could visually and accurately display the shape and spatial extent of hilar cholangiocarcinoma. It has an important clinical use in accurately diagnosing hilar cholangiocarcinoma preoperatively.

Research progress of Traditional Chinese Medicine on treating primary bronchial lung cancer / 国际中医中药杂志

The clinical effect of Traditional Chinese Medicine (TCM) in the treatment of primary bronchial lung cancer is good. To a certain extent, TCM can control the progress of the disease and improve quality of life by the treatment of syndrome differentiation, disease-modified prescription, experience prescription, Chinese patent medicine, TCM injection, acupuncture and acupoint application, which have been combined with chemotherapy. The mechanism of TCM in the treatment of primary bronchial lung cancer mainly includes inhibition of lung cancer cell proliferation, induction of lung cancer cell apoptosis, improvement of body immunity and overcoming chemotherapy resistance.

Diagnosis and treatment of systemic sclerosis-associated interstitial lung disease: current status and advances / 中华皮肤科杂志

Systemic sclerosis (SSc) is a rare, chronic connective tissue disease with internal organ fibrosis, and interstitial lung disease (ILD) is the leading cause of death in patients with SSc. The onset of SSc-associated ILD is usually latent, and delayed treatment may lead to rapid progression, and markedly decrease the quality of life and survival rate of patients. This review summarizes approaches to the early diagnosis of SSc-associated ILD and the time-to-treatment, and provides an overview of its treatment, including traditional immunosuppressive agents, newly emerging targeted therapies, hematopoietic stem cell transplantation, lung transplantation, and so on.

Diagnosis and treatment of systemic sclerosis-associated interstitial lung disease: current status and advances / 中华皮肤科杂志

Systemic sclerosis (SSc) is a rare,chronic connective tissue disease with internal organ fibrosis,and interstitial lung disease (ILD) is the leading cause of death in patients with SSc.The onset of SSc-associated ILD is usually latent,and delayed treatment may lead to rapid progression,and markedly decrease the quality of life and survival rate of patients.This review summarizes approaches to the early diagnosis of SSc-associated ILD and the time-to-treatment,and provides an overview of its treatment,including traditional immunosuppressive agents,newly emerging targeted therapies,hematopoietic stem cell transplantation,lung transplantation,and so on.

Three-dimensional computer reconstruction in hemihepatectomy / 中华肝胆外科杂志

Objective:To study preoperative three-dimensional computer reconstruction in hemihepatectomy.Methods:The clinical data of patients who underwent hemihepatectomy at Affiliated Provincial Hospital of Anhui Medical University from January 2017 to August 2019 was retrospectively analyzed. Of 68 patients, there were 33 males and 35 females. The average age was 60.1 years. Based on whether the patients underwent preoperative three-dimensional computer reconstruction, these patients were divided into the three-dimensional group ( n=30) and the control group ( n=38). The coincidence rates of preoperative diagnosis by imaging, vascular types and preoperative in relation to intraoperative findings between the two groups were compared. Results:Using intraoperative findings as the gold standard, the coincidence rates of preoperative imaging diagnosis of cholelithiasis, hilar cholangiocarcinoma and intrahepatic space occupying lesions were 96.7% (29/30) in the three-dimensional group, and 94.7% (36/38) in the control group. There was no significant difference between the two groups ( P>0.05). Using intraoperative or anatomic specimens findings, the coincidence rates of preoperative evaluation of portal vein and bile duct in the three-dimensional group were 93.3% (28/30) and 96.7% (29/30) respectively. The corresponding rates for the control group were 73.7% (28/38) and 79.0% (30/38) respectively. Furthermore, the coincidence rates of liver volume were 96.7% (29/30) in the three-dimensional group and 79.0% (30/38) in the control group. Assessments on portal vein, bile duct and liver volumes were significantly better in the three dimensional group than the control group ( P<0.05). Conclusion:Preoperative three-dimensional computer reconstruction better diagnosed hilar space occupying lesions and hepatolithiasis, and more accurately delineated vascular courses. All these had important clinical impact on hemihepatectomy.

Cereblon Deletion Ameliorates Lipopolysaccharide-induced Proinflammatory Cytokines through 5′-Adenosine Monophosphate-Activated Protein Kinase/Heme Oxygenase-1 Activation in ARPE-19 Cells

Cereblon (CRBN), a negative modulator of AMP-activated protein kinase (AMPK), is highly expressed in the retina. We confirmed the expression of CRBN in ARPE-19 human retinal cells by Western blotting. We also demonstrated that CRBN knock-down (KD) could effectively downregulate IL-6 and MCP-1 protein and gene expression in LPS-stimulated ARPE-19 cells. Additionally, CRBN KD increased the phosphorylation of AMPK/acetyl-coenzyme A carboxylase (ACC) and the expression of heme oxygenase-1 (HO-1) in ARPE-19 cells. Furthermore, CRBN KD significantly reduced LPS-induced nuclear translocation of NF-κB p65 and activation of NF-κB promoter activity. However, these processes could be inactivated by compound C (inhibitor of AMPK) and zinc protoporphyrin-1 (ZnPP-1; inhibitor of HO-1). In conclusion, compound C and ZnPP-1 can rescue LPS-induced levels of proinflammatory cytokines (IL-6 and MCP-1) in CRBN KD ARPE-19 cells. Our data demonstrate that CRBN deficiency negatively regulates proinflammatory cytokines via the activation of AMPK/HO-1 in the retina.

Design, synthesis and biological activity of novel triazine inhibitors of Candida albicans secreted aspartic protease 2 / 药学学报

In recent years, the incidence and mortality of invasive fungal infections has increased. It is highly desirable to develop novel antifungal agents with new modes of action. Targeting virulence factors represents a new strategy for antifungal drug discovery. Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging antifungal target. However, discovery of small-molecule SAP2 inhibitors remains a significant challenge. Based on the structure-activity relationship of our previously identified triazine small-molecule SAP2 inhibitor, we were able to identify two potent inhibitors, 8a and 8c, which showed excellent in vivo antifungal activity for the treatment of C. albicans infection. Moreover, compounds 8a and 8b effectively inhibited fungal biofilm. Taken together, triazine SAP2 inhibitors represent promising lead compounds for the discovery of novel antifungal agents.

Effect evaluation of interventional training of working memory on children with developmental dyslexia / 中国学校卫生

Objective@#To explore the effect of working memory intervention training on working memory and literacy of children with developmental dyslexia,so as to provide a preference for practice of the trianing of working memory among children with dyslexia.@*Methods@#A total of 32 children with dyslexia of grade 3-5 in a primary school in Guiyang were randomly divided into two groups: the study group (n=16) and the control group (n=16),and the software of training exercises of working memory was applied to conduct interventional trainings of different durations to 2 gruops of children.@*Results@#Through the intervention training of working memory, the scores of literacy and working memory tasks in the study group (2 217.88±252.32, 105.13±7.68) were significantly higher than those in the control group (1 907.69 ± 545.15, 96.50 ± 11.04) (t=2.06, 2.56, P<0.05).@*Conclusion@#The working memory ability of children with dyslexia can be improved by working memory intervention training for a certain period of time. The intervention effect is not only significant in the trained working memory task, but also can be extended to other untrained contents such as literacy.

Clinical efficacy of immunonutrition support in perioperative period of hepatectomy: a Meta analysis / 中华消化外科杂志

Objective@#To systematically evaluate the clinical efficacy of immunonutrition support in perioperative period of hepatectomy.@*Methods@#Literatures were researched using CNKI，CBM，Wanfang database，VIP databases，PubMed (Medline)，Embase，Web of science，Science Direct，Cochrane Center from January 1996 to March 2018 with the key words including "肝切除术，免疫营养，hepatectomy，hepatic resection，immunonutrition，immunoenhanced nutrition" . The randomized controlled trials (RCTs) on comparison of efficacy of immunonutrition support versus routine nutritional support in perioperative period of hepatectomy. Patients in the immunonutrition group received immunonutrition support in perioperative period of hepatectomy，and patients in the routine nutrition group received routine nutritional support in perioperative period of hepatectomy. Outcome measures：overall incidence of postoperative complications，incidence of postoperative infectious complications，incidence of postoperative liver failure，perioperative mortality，hospital stay，and hospitalization expenses. Literatures screening，data extraction and quality assessment of methodology were conducted by two researchers separately. Count data were represented as risk ratio (RR) and 95% confidence interval (CI). Measurement data were represented as mean difference (MD) or weighted mean difference (WMD) and 95%CI. Heterogeneity of the included studies was analyzed with I2. Funnel plot was used to test potential publication bias if the number of studies included ≥ 10，and funnel plot was used to test potential publication bias for the outcome measures with the maximum number of studies if the number of studies included <10.@*Results@#(1) Document retrival: 12 RCTs were enrolled in the Meta analysis, and the total sample size was 1 136 patients, including 568 patients in the immunonutrition group and in the routine nutrition group, respectively. (2) Results of Meta-analysis: the that immunonutrition group had lower overall incidence of postoperative complications, incidence of postoperative infectious complications, incidence of postoperative liver failure, and hospital stay (RR=0.57, 0.49, 0.30, MD=-3.28, 95%CI: 0.46-0.71, 0.37-0.65, 0.12-0.74, -4.45 to -2.11, P<0.05), and higher hospital expenses (MD=11.86, 95%CI: 10.96-12.77, P<0.05) compared with the routine nutrition group. There was no significant difference in the perioperative mortality between the two groups (RR=0.26, 95%CI: 0.07-1.05, P>0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies comparing incidence of postoperative infectious complications between the immunonutrition group and routine nutrition group, suggesting that publication bias had little influence on results of Meta-analysis.@*Conclusions@#Perioperative immunonutrition support for hepatectomy is safe and feasible. Compared with routine nutritional support, immunonutrition support can significantly reduce overall incidence of postoperative complications, incidence of postoperative infectious complications, incidence of postoperative liver failure, and shorten the hospital stay without increasing postoperative mortality.

Clinical efficacy of immunonutrition support in perioperative period of hepatectomy: a Meta analysis / 中华消化外科杂志

Objective To systematically evaluate the clinical efficacy of immunonutrition support in perioperative period of hepatectomy.Methods Literatures were researched using CNKI,CBM,Wanfang database,VIP databases,PubMed (Medline),Embase,Web of science,Science Direct,Cochrane Center from January 1996 to March 2018 with the key words including " 肝切除术,免疫营养,hepatectomy,hepatic resection,immunonutrition,immunoenhanced nutrition".The randomized controlled trials (RCTs) on comparison of efficacy of immunonutrition support versus routine nutritional support in perioperative period of hepatectomy.Patients in the immunonutrition group received immunonutrition support in perioperative period of hepatectomy,and patients in the routine nutrition group received routine nutritional support in perioperative period of hepatectomy.Outcome measures:overall incidence of postoperative complications,incidence of postoperative infectious complications,incidence of postoperative liver failure,perioperative mortality,hospital stay,and hospitalization expenses.Literatures screening,data extraction and quality assessment of methodology were conducted by two researchers separately.Count data were represented as risk ratio (RR) and 95％ confidence interval (CI).Measurement data were represented as mean difference (MD) or weighted mean difference (WMD) and 95％CL Heterogeneity of the included studies was analyzed with I2.Funnel plot was used to test potential publication bias if the number of studies included ≥ 10,and funnel plot was used to test potential publication bias for the outcome measures with the maximum number of studies if the number of studies included ＜ 10.Results (1) Document retrival:12 RCTs were enrolled in the Meta analysis,and the total sample size was 1 136 patients,including 568 patients in the immunonutrition group and in the routine nutrition group,respectively.(2) Results of Meta-analysis:the that immunonutrition group had lower overall incidence of postoperative complications,incidence of postoperative infectious complications,incidence of postoperative liver failure,and hospital stay (RR =0.57,0.49,0.30,MD=-3.28,95％CI:0.46-0.71,0.37-0.65,0.12-0.74,-4.45 to-2.11,P＜0.05),and higher hospital expenses (MD =11.86,95％CI:10.96-12.77,P＜0.05) compared with the routine nutrition group.There was no significant difference in the perioperative mortality between the two groups (RR=0.26,95％ CI:0.07-1.05,P＞0.05).The bilateral symmetry was presented in the funnel plot based on the 9 studies comparing incidence of postoperative infectious complications between the immunonutrition group and routine nutrition group,suggesting that publication bias had little influence on results of Meta-analysis.Conclusions Perioperative immunonutrition support for hepatectomy is safe and feasible.Compared with routine nutritional support,immunonutrition support can significantly reduce overall incidence of postoperative complications,incidence of postoperative infectious complications,incidence of postoperative liver failure,and shorten the hospital stay without increasing postoperative mortality.

Therapeutic effects of baicalin on lupus nephritis in a lupus-prone mouse model and its regulatory role in follicular helper T cell differentiation / 中华皮肤科杂志

Objective To evaluate the therapeutic effect of baicalin on lupus nephritis in a lupusprone mouse model,and to investigate its regulatory role in the differentiation of follicular helper T (Tfh)cells.Methods Eight 12-week-old female MRL/lpr lupus-prone mice were randomly and equally divided into two groups by a random number table i.e.,baicalin group and control group intraperitoneally injected with 200 mg/kg baicalin sodium and chloride physiological solution,respectively,once every day for 4 weeks.After the end of treatment,Coomassie brilliant blue staining was performed to detect the level of 24-hour urine protein.Then,the mice were sacrificed,and the spleens were resected and weighed.Mononuclear cells were isolated from these spleens,and flow cytometry was conducted to determine the proportion of Tfh cells.Additionally,the kidneys were resected and subjected to hematoxylin and eosin (HE) staining for the evaluation of kidney impairment.Moreover,some other mononuclear cells were isolated from the spleens of the lupus-prone mice in the control group,and magnetic activated cell sorting (MACS) was performed to isolate naive CD4+ T cells,which were divided into 3 groups:blank control group receiving no treatment,induction group treated with 10 μg/L anti-interleukin (IL)-21 and anti-IL-6 antibodies and 3 μg/L anti-CD3 and anti-CD28 antibodies for 5 days,and intervention group additionally treated with 40 μmol/L baicalin for 5 days besides the above treatment.Then,50 μg/L phorbol ester,750 μg/L ionomycin and 20 mg/L brefeldin A were used to stimulate some cultured naive CD4+ T cells in the above groups.Flow cytometry was conducted to determine the proportion of CD4+CXCR5+PD-1 + cells and CD4+IL-21+ cells.Statistical analysis was carried out with SPSS20.0 software by using one-way analysis of variance (ANOVA) and student t test for the comparison of quantitative data between groups.Results The baicalin treatment could effectively improve the kidney impairment in the lupus-prone mice.Compared with the control group,the baicalin group showed significantly decreased 24-hour urine protein level ([1 416 ± 171] vs.[2 623 ± 278] μg/24 h,P =0.022),and significantly decreased proportion of Tfh cells in the spleen (12.6％ ± 2.3％ vs.40.2％ + 1.1％,P =0.005).In vitro baicalin could further inhibit the differentiation of Tfh cells.Compared with the induction group,the intervention group showed significantly decreased proportion of CD4+CXCR5+PD-1+ Tfh cells (13.3％ ± 0.8％ vs.17.6％ ± 0.9％,P =0.04) and CD4+IL-21+ cells (1.0％ ± 0.4％ vs.2.7％ ± 0.2％,P ＜ 0.01).Conclusion Baicalin can effectively ameliorate lupus nephritis,which may be associated with the inhibition of Tfh cell differentiation.

The effect of entinostat on NK killing effect on non-small cell lung cancer in vitro / 中国肿瘤临床

Objective: To investigate the Effects of entinostat on the expression of NKG2D ligands in the non-small cell lung cancer (NSCLC) cell lines, A549 and HCC-827, and to detect the effect of entinostat-mediated NK cell killing of A549 and HCC-827 cells. Meth-ods: The effect of entinostat on A549 and HCC-827 cell proliferation was measured by MTT assay. Flow cytometry was used to detect the expression of NKG2D ligands. mRNA levels of the ligands were detected by RT-PCR . The level of soluble MICA in cell culture super-natant was evaluated by ELISA. The cytotoxicity of NK cells against A549 and HCC-827 cell lines (treated with entinostat) was assessed using lactate dehydrogenase release assay. Results: Entinostat showed a time-and dose-dependent inhibition effect on the prolifera-tion of A549 and HCC-827 cell lines. The expression of NKG2D ligands and mRNA transcription levels of MICA and MICB were en-hanced after treatment with 0.5, 1μmol/L entinostat for 48 h. The soluble MICA level in A549 cell culture supernatant was increased by 1μmol/L entinostat. The sensitivity of HCC-827 cells to NK cells was enhanced upon treatment with 0.5, 1μmol/L entinostat. Con-clusions: entinostat enhanced the killing effect of NK cells on non-small cell lung cancer cells by up-regulating the expression of NKG2D ligands. This provides a new method and theory for the treatment of NSCLC.