Expression and significance of immune cells in patients with hepatitis B virus-related acute-on-chronic pre-liver failure / 临床肝胆病杂志

Objective To investigate the expression of myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), IL-17-producing CD4 + T cells (Th17), and CD8 + T cells (Tc17) in hepatitis B virus-related acute-on-chronic pre-liver failure (pre-ACHBLF), and to provide ideas for the early treatment of acute-on-chronic hepatitis B liver failure (ACHBLF). Methods A total of patients with pre-ACHBLF and 15 patients with ACHBLF who were hospitalized in Shijiazhuang Fifth Hospital, from August 2018 to May 2019 were enrolled as subjects, and 15 patients with chronic hepatitis B (CHB) and 15 healthy controls (HC) who underwent physical examination were enrolled as controls. Flow cytometry was used to measure the expression levels of MDSC and Th17, Treg, and Tc17 cells in peripheral blood; a blood analyzer was used to measure routine blood parameters and calculate neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index(SIRS) to evaluate the degree of inflammation, and the correlation between the expression of immune cells and the degree of inflammation was analyzed. An analysis of variance for independent samples was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Nemenyi test was used for further comparison between two groups. A Pearson linear correlation analysis or Spearman's rank correlation analysis was used to investigate the correlation between variables. Results Compared with the CHB group, the ACHBLF and pre-ACHBLF groups had significant increases in the expression levels of Th17, Treg, and Tc17 cells, and the pre-ACHBLF group also had a significant increase in the expression level of MDSC (all P < 0.05). The correlation analysis showed that in pre-ACHBLF patients, MDSC were positively correlated with leukocyte count, neutrophil count, NLR, MLR, and SII ( r =0.775, 0.727, 0.571, 0.786, and 0.846, all P < 0.05), and Treg cells were only positively correlated with leukocyte count ( r =0.618, P =0.043); Th17/Treg ratio and Tc17 cells were negatively correlated with the number of lymphocytes ( r =-0.790 and -0.795, both P < 0.05). Conclusion Cellular immune dysfunction is observed in patients with pre-ACHBLF, and the expression of MDSC is closely associated with the degree of inflammation and should be taken seriously in the early stage.

The diagnostic value of glucose transporter 1 level of erythrocyte membrane and glucose uptake rate of erythrocytes in glucose transporter type 1 deficiency syndrome / 中华实用儿科临床杂志

Objective:To explore new methods to assist the diagnosis of glucose transporter type 1 deficiency syndrome (GLUT1-DS).Methods:Sixteen children with epilepsy and/or movement disorder carrying the SLC2A1 mutation who admitted to Department of Pediatrics, the First Medical Center, Chinese People′s Liberation Army General Hospital and Department of Nutrition, Shanghai Deji Hospital from October 2019 to October 2020 were retrospectively analyzed.GLUT1-DS was diagnosed based on clinical phenotype, glucose level in CSF and/or genetic testing results.Forty-four healthy children who underwent physical examination in the First Medical Center, Chinese People′s Liberation Army General Hospital during the same period were selected as healthy control group.Glucose transporter 1 (GLUT1) level on the membrane surface of peripheral red blood cells and erythrocyte glucose uptake rate were measured by flow cytometry and glucose oxidase method, respectively.Their differences between groups were compared by the rank sum test.The receiver operating cha-racteristic (ROC) curve was plotted to assess their diagnostic value. Results:Sixteen children were diagnosed as GLUT1-DS.GLUT1 levels of 16 children with GLUT1-DS were significantly lower than those of healthy control group [17.96% (13.43%, 22.12%) vs.27.93% (24.76%, 34.30%), Z=5.249, P<0.001]. Area under curve (AUC) was 0.946, and weighted Kappa was 0.791 ( P<0.001). The erythrocyte glucose uptake was measured in 12 children with GLUT1-DS, which was significantly lower than that of healthy control group [23.14% (14.80%, 26.45%) vs.27.40% (24.61%, 32.82%), Z=2.366, P=0.018]. AUC and weighted Kappa were 0.724 and 0.344, respectively ( P<0.001), showing a poor consistency. Conclusions:GLUT1 level on the surface of human erythrocyte membrane measured by flow cytometry may be a new method to assist the diagnosis of GLUT1-DS.The erythrocyte glucose uptake rate test requires stricter experimental conditions and needs further investigation.

Analysis of differences in gut microbiota in patients with chronic spontaneous urticaria by 16S rRNA high-throughput sequencing / 中华皮肤科杂志

Objective:To investigate differences in gut microbiota between patients with chronic spontaneous urticaria (CSU) and healthy controls.Methods:A total of 18 patients with CSU (CSU group) and 18 age- and gender-matched healthy controls (HC group) were enrolled from Department of Dermatology, Tianjin First Central Hospital between January 2019 and December 2019. Fecal samples were collected from these subjects, and total DNA was extracted. The 16S rRNA sequencing technology was used to identify microbial species in gut microbiota, and bioinformatics methods were applied to analyze differences in gut microbiota composition between the 2 groups. The SPSS 23.0 software was used for statistical analysis of the experimental data.Results:In terms of α diversity, there was no significant difference in the Observed OTU index, Chao1 index, Shannon index or Simpson index between the CSU group (161.28 ± 35.47, 161.31 ± 35.51, 5.15 ± 0.47, 0.94 ± 0.03, respectively) and HC group (154.89 ± 54.46, 154.92 ± 54.43, 4.92 ± 0.88, 0.91 ± 0.08, respectively; t = 0.417, 0.417, 0.952, 1.116, respectively, all P > 0.05) . In terms of β diversity, principal component analysis showed that the first and second principal components explained 6.66% and 4.93% respectively, and there was no significant difference in the microbiota structure between the 2 groups ( P = 0.672) . The relative abundance of the genus Holdemania in the gut microbiota significantly differed between the CSU group and HC group (0.04% vs. 0.01%, P = 0.025) . Conclusion:The gut microbiota differs between the patients with CSU and healthy controls.

Compare the clinical value between the current reference interval and the original interval for serum creatinine / 中华检验医学杂志

Objective:Explored the clinical application value of the current reference interval of serum creatinine (using the 2015 health industry standard) and the original reference interval (using the third edition of the clinical laboratory operating procedures).Methods:This paper is a retrospective study. The study collected 360 normal serum samples of the adults who visited the First Hospital of Hebei Medical University from February to April 2019 and,aged 20-79 years old (including 90 males aged 20-59, 90 females aged 20-59, 90 males aged 60-79, and 90 females aged 60-79). The concentration of cystatin C was determined in the above specimens, combined with the concentration of creatinine, and the results calculated by the Glomerular Filtration Rate Estimation Formula (eGFR) was used as the standard for judgment. In this study, the chi-square test was used to statistically analyze the agreement between the results of the new and old reference intervals of creatinine and the results calculated by the eGFR formula.Results:The total coincidence rate of Scr and eGFR in 360 adults aged 20-79 years was 83.40% in the current RI, and 77.00% in the original RI. The coincidence rate of the former was significantly higher than that of the latter ( P=0.03). The positive coincidence rate of Scr and eGFR (214 patients with eGFR positive) was 91.86% in current RI, 41.59% in the original RI, the coincidence rate of the former was significantly higher than that of the latter ( P<0.01). The negative coincidence rate of Scr and eGFR (146 patients with eGFR negative) was 74.66% in current RI, and 99.32% in original RI, the coincidence rate of the latter was significantly higher than that of the former ( P<0.01). Consistent results were shown in groups of males aged 20-59, females aged 20-59 and females aged 60-79. However, in the group of males aged 60-79 years, the total coincidence rate of Scr and eGFR was 75.56% in current RI, and 88.89% in original RI, the coincidence rate of the latter was significantly higher than that of the former ( P =0.01); positive coincidence rate of Scr and eGFR was 57.69% in current RI, and 98.08% in original RI, the coincidence rate of the latter was significantly higher than that of the former ( P<0.01); negative coincidence rate of Scr and eGFR was 100.0% in current RI, and 76.32% in original RI, the coincidence rate of the former was significantly higher than that of the latter ( P<0.01). Conclusions:The current reference interval is better than the original reference interval in screening for decreased glomerular filtration rate, and it is favorable for the early detection of patients with mildly decreased renal function. However, among males aged 60-79 years old, the accuracy of the current RI and the ability to screen for decreased glomerular filtration rate are inferior to the original RI, which needs to be further observed and studied.

Mechanism of action of forkhead box transcription factors in hepatocellular carcinoma and their prospects as treatment targets / 临床肝胆病杂志

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers and has high incidence and mortality rates and poor prognosis. Forkhead box (FOX) transcription factor family can regulate cell growth, differentiation, and tissue development and plays an important role in tumor. This article reviews the association of the molecular expression of the FOX family with the development, progression, and prognosis of HCC and analyzes the mechanism of action of FOX in the progression of HCC. It is pointed out that FOX family is expected to become a new target for HCC treatment.

Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals

BackgroundLymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. MethodsA clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. FindingsCompared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. InterpretationThe CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions. FundingKunming Science and Technology Department (2020-1-N-037)

Impaired T cell functions along with elevated activated Tregs at the early stage of asymptomatic SARS-CoV-2 infection

BackgroundLimited data are available on the T cell responses for the asymptomatic SARS-CoV-2 infection case. MethodsAn imported SARS-CoV-2 infection case in Wuhan was admitted in hospital for quarantine and observation. The T cell responses were followed up by flow cytometry analysis of the peripheral blood nonnuclear cells (PBMCs) at days 7, 13, 22, and 28 after admission. FindingsWe found the imported SARS-CoV-2 infection in Wuhan is an asymptomatic case. His T cell differentiation, proliferation and activation matched the classical kinetics of T cell responses induced by viral infection, but the activation maintained at a relatively low level. Function analysis indicated frequencies of IFN-{gamma} producing CD4+ and CD8+ T cells were notably lower than that of the healthy controls (HC) at day 7, and then rebound gradually. But IFN-{gamma}+CD8+ T cells were detained at a significant lower level even at day 28, when the SARS-CoV-2 virus had already become undetectable for 3 weeks. Moreover, percentage of IL-17 producing CD4+ T cells was also detained constantly at a much lower level compared to HC. At day 7, although percentage of Tregs was in normal range, the frequency of activated Treg (aTreg) was remarkably as high as 4{middle dot}4-fold of that in HC. InterpretationThe T cell activation in the asymptomatic SARS-CoV-2 infection experienced a significant suppression and presented impairment of Th1/Th17 and CD8+ T cell functions. Early elevation of the aTregs might play role in the activation and function of T cells in the asymptomatic SARS-CoV-2 infection.

Qualitative research of high intensity interval training experience in type 2 diabetes / 中国实用护理杂志

Objective:To understand the understanding and experience of high intensity interval training (HIIT/HIT) in patients with type 2 diabetes mellitus (T2DM), analyze the influencing factors of patients′ participation in the treatment prescription, and provide references for the formulation of the exercise plan and the implementation of targeted nursing.Methods:Totally 11 cases of T2DM HIIT patients admitted to the department of endocrinology, a third-class first-class hospital in Qingdao from March to November 2019 were interviewed in a semi-structured way, and the data were analyzed and extracted using the phenomenological research method.Results:A total of three themes and 10 subjective themes were extracted. Subjective experience: positive emotional experience, the recognition HIIT is inconsistent, duration and high intensity load cycles affect sports enthusiasm, the discomfort of original changes in lifestyle); promoting factor: movement time, stable blood sugar control, simple is not restricted by the natural environment and economy; hindering factors: social role pressure, insufficient strengthened intervention of stimulus, worrying about an accident.Conclusion:There are promoting factors and obstacles in the process of high intensity intermittent motion in patients with type 2 diabetes, but its strong knowledge for sports consciousness and the hope of diversification, medical personnel can timely give intervention and correct guidance to help patients correct implementation plan, improve the exercise adherence, better control of blood sugar, prevent and delay the development of complications.

Research advances in endoscopic treatment of esophageal and gastric varices / 临床肝胆病杂志

Gastroesophageal variceal bleeding is one of the most common and critical complications of liver cirrhosis, with high rebleeding and mortality rates. Esophageal and gastric varices is a special type of varices, and endoscopic treatment methods for this disease include endoscopic variceal sclerotherapy, endoscopic tissue adhesive injection, and combined sequential therapy, but there are still controversies over the selection of specific treatment method. This article reviews the recent research advances in the endoscopic treatment of esophageal and gastric varices in China and foreign countries.

A study regarding the control attempts on body weight and related factors among overweight and obese adults in China, 2013 / 中华流行病学杂志

Objective@#To understand the control attempts of body weight and its related factors among overweight and obese adults in China.@*Methods@#Data was from the 2013 Chinese Chronic Diseases and Risk Factors Surveillance Program, which covered 302 surveillance sites. 179 570 adults, selected through multistage stratified cluster sampling method, were interviewed. Demographic characteristics and weight-control attempts were collected via face-to-face interview. BMI, waist circumstance and blood pressure were individually measured under physical examination. Venous blood samples were obtained and tested for FPG, OGTT-2h, TC, TG, LDL-C and HDL-C. A total of 87 545 overweight and obese patients were included in this study, with the exclusion of 152 patients having the missed critical information. Rates on weight control and attempts were analyzed, using the complex weighting on samples to represent the overall overweight and obese adults in China.@*Results@#The rate of weight-control attempts was 16.3% (95%CI: 14.9%-17.7%). Among all the 12 133 patients who had undergone weight-control measures, the proportions of different attempts were as follows: diet (40.9%, 95%CI: 38.4%-43.3%), combination of diet and physical activity (31.5%, 95%CI: 28.9%-34.0%), physical activity (22.8%, 95%CI: 21.0%-24.6%) and drug control (1.3%, 95%CI: 1.0%-1.7%). Factors as: being female (OR=1.26, 95%CI: 1.15-1.38), at younger age (18-44 years old, OR=1.51, 95%CI: 1.31-1.74), with high education levels (college degree or above, OR=4.52, 95%CI: 3.76-5.43), having high annual income (≥24 000 Yuan, OR=1.94, 95%CI: 1.63-2.30) etc., appeared as favorable factors for taking the measures vs. rural residency (OR=0.63, 95%CI: 0.55- 0.72) as the unfavorable one.@*Conclusion@#The rate of weight-control attempts appeared low among the overweight and obese adults who were affected by factors as age, education and income level. Personalized intervention measures should be carried out for people with different characteristics.

Study of epidemiological characteristics of metabolic syndrome and influencing factors in elderly people in China / 中华流行病学杂志

Objective@#To estimate the prevalence of MS in elderly people aged ≥60 years and its related factors in China and provide scientific evidence for prevention and control of MS in the elderly.@*Methods@#Data used in this study were obtained from the 2013 Chinese Chronic Diseases and Risk Factor Surveillance Program. A total of 50 497 people aged ≥60 years were selected and interviewed through multistage stratified cluster sampling at 298 surveillance sites in 31 provinces. According to the Chinese MS diagnostic criteria proposed by the Chinese Medical Association Diabetes Branch in 2017, the prevalence rates of different MS forms were compared, and the main related factors were analyzed.@*Results@#The prevalence rate of MS was 36.9% (95%CI: 35.4-38.5). The prevalence rate was higher in urban area than in the rural area, higher in females than in males, higher in eastern area than in western area. The prevalence rate of MS in elderly people aged ≥70 years was lower than that in those aged 60-69 years. The rate in the elderly with higher education and income levels was higher than that in the elderly with lower socioeconomic level. The comparison of the prevalence of the five forms of MS in the elderly showed that hypertension had the highest prevalence rate (72.8%), followed by hyperglycemia (41.7%) and central obesity (37.6%). The prevalence rates of hypertriglyceridemia and low HDL-C were 25.8% and 17.5%. The risk for MS in women was 1.20 times higher than that in men. Age, gender, education level, living area and urban or rural residence were the main factors influencing the prevalence of MS. Smoking, drinking and physical activity levels were correlated with MS.@*Conclusions@#The risk for MS was higher in women than in men in China’s elderly population, and the risk was related to socioeconomic level and life behaviors. It is recommended to carry out lifestyle interventions, such as increasing exercise and having reasonable diet for the elderly patients with MS. Hypertension and diabetes patients also need to be treated with drugs to reduce the risk of cardiovascular disease morbidity and mortality.

Etiology of community-acquired pneumonia in 1500 hospitalized children.

Childhood community-acquired pneumonia (CAP) is a common illness; however, comprehensive studies of hospitalizations for CAP among children in China based on prospective and multicenter data collection are limited. The aim of this investigation was to determine the respiratory pathogens responsible for CAP in hospitalized children. From January to December 2015, oropharyngeal swabs and blood serum were collected from hospitalized children with CAP symptoms ranging in age from 6 months to 14 years at 10 hospitals across China. We used immunofluorescence to detect antibodies for eight respiratory viruses and passive agglutination to detect specific IgM against Mycoplasma pneumoniae (M. pneumoniae). Of 1500 children presenting with CAP, 691 (46.1%) tested positive for at least one pathogen (virus or M. pneumoniae). M. pneumoniae (32.4%) was detected most frequently, followed by respiratory syncytial virus (11.5%), adenovirus (5.0%), influenza A virus (4.1 %), influenza B virus (3.4%), parainfluenza virus types 2 and 3 type (3.1 %), parainfluenza virus type 1 (2.9%), and human metapneumovirus (0.3%). Co-infections were identified in 128 (18.5%) of the 691 cases. These data provide a better understanding of viral etiology and M. pneumoniae in CAP in children between 6 months and 14 years in China. More study of the etiologic investigations that would further aid the management of pneumonia is required. With effective immunization for RSV, ADV, and M. pneumoniae infections, more than one-half of the pneumonia cases in this study could have been prevented.

Clinical effect of endoscopic dense ligation in treatment of esophageal variceal bleeding / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect of endoscopic dense ligation in the treatment of esophageal variceal bleeding. MethodsA total of 156 patients who underwent endoscopic ligation for the first time due to esophageal variceal bleeding caused by cirrhotic portal hypertension in Shijiazhuang Fifth Hospital from July 2015 to June 2016 were enrolled, and according to the treatment method, they were divided into dense ligation group with 76 patients and non-dense ligation group with 80 patients. The patients were followed up for 1-2 years, and a statistical analysis was performed for the eradication or disappearance rate of varices, the number of times of ligation, early rebleeding rate, late-onset rebleeding rate, and the incidence rate of adverse reactions. The t-test was used for comparison of continuous data between two groups, and the chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. ResultsThere were significant differences between the dense ligation group and the non-dense ligation group in the eradication or disappearance rate of varices (71.05% vs 55.00%, χ2=4.300, P=0.038) and number of times of ligation (χ2=8.511, P=0.014), and there were no significant differences between the two groups in early rebleeding rate (5.26% vs 2.50%, P＞0.05), late-onset rebleeding rate (7.89% vs 10.00%, P＞0.05), recurrence rate of varices (13.16% vs 18.75%, P＞0.05), and incidence rate of adverse reactions (26.32% vs 21.25%, P＞0.05). There was a significant difference in the time to recurrence of varices between the two groups (11.90±1.89 months vs 7.07±1.17 months, t=2.295, P=0.031). Of all 156 patients, 2 (1.28%) died during follow-up, with 1 patient in the dense ligation group and 1 in the non-dense ligation group. There was no significant difference in mortality rate between the two groups (P＞0.05). ConclusionEndoscopic dense ligation is a safe technique for the treatment of esophageal variceal bleeding and is better than non-dense ligation in terms of the disappearance rate of varices and number of times of ligation. Endoscopic dense ligation also allows a longer time to recurrence of varices than non-dense ligation.

Mutation analysis of the PNPLA1 gene in a family with autosomal recessive congenital ichthyosis / 中华皮肤科杂志

Objective To identify a causative gene of autosomal recessive congenital ichthyosis (ARCI) in a Chinese family,and to analyze the genotype-phenotype correlation.Methods Peripheral blood samples were collected from the proband,his elder brother and parents,and genomic DNA was extracted from these blood samples.Genome-wide exome sequencing was conducted to determine the mutation site in the proband,and then allele-specific oligonucleotide primers were designed based on the mutation site.PCR was performed to detect the mutation site to further identify the causative gene of ARCI in the family.Results A new homozygous missense mutation was identified in exon 4 in 1 allele of the PNPLA1 gene in the proband,which led to a codon change from cytosine (C) to thymine (T) at position 700 (c.700C ＞ T) and resulted in the substitution of proline by serine (p.pro234ser).The same mutation was also detected in the proband's brother,and his parents were the mutation carriers.No mutations were found in unrelated healthy Chinese individuals.Conclusion The missense mutation in the PNPLA1 gene (p.pro234ser) is associated with clinical symptoms of the patient with ARCI.

High-throughput sequencing analysis of gut microbiome in patients with severe acne vulgaris and healthy individuals / 中华皮肤科杂志

Objective To compare differences of gut microbiome between patients with severe acne vulgaris and healthy individuals by using high-throughput sequencing technology.Methods Stool samples were collected from 10 outpatients with severe acne vulgaris and 10 age-and sex-matched healthy controls.Then,the bacterial DNA was extracted and subjected to 16S rRNA sequencing for the identification of microbial species,and the differences of gut microbiome were compared between the patients and controls.Results There were no significant differences in the diversity of intestinal microflora,but only the relative abundance of a few bacteria differed significantly between the two groups.Gut microbiome in the two groups mainly consisted of Bacteroidetes,Firmicutes,Proteobacteria and Actinobacteria.There were no significant differences in the relative abundance of bacteria at the phylum and genus levels between the two groups.However,the relative abundance of Blautia producta and Coprococcus eutactus at the species level differed remarkably between the two groups.Conclusion No significant differences in the bacterial diversity indices are found,but some bacterial species significantly differ between the patients with severe acne vulgaris and healthy controls.

Mutation analysis of the OSMR gene in two Chinese families with familial primary cutaneous amyloidosis / 中华皮肤科杂志

Objective To detect mutations in the OSMR gene in 2 Chinese families with familial primary cutaneous amyloidosis (FPCA),and to analyze their relationship with clinical manifestations.Methods Clinical data were collected from 2 families with FPCA,and genomic DNA was extracted from peripheral blood samples.PCR was performed to amplify 18 exons and their flanking sequences of the OSMR gene followed by DNA sequencing in 2 probands and their family members.One hundred healthy individuals served as controls.Results In the first family,a heterozygous mutation (c.2081C ＞ T) in exon 15 of the OSMR gene,which leads to a codon change at amino acid position 694 (p.P694L),was identified in the proband,as well as in the other 4 patients.In the second family,a heterozygous mutation (c.1538G ＞A) in exon 11 of the OSMR gene,which causes a codon change at amino acid position 513 (p.G513D),was identified in the other proband and her mother,suggesting the cosegregation of the gene mutation with the disease.None of the above mutations were detected in the healthy family members or controls.Conclusion The heterozygous mutations p.P694L and p.G513D in the OSMR gene may be associated with primary cutaneous amyloidosis.

The advantages and research progress of T cells of the chimeric antigen receptor in the treatment of primary tumors / 天津医药

Chimeric antigen receptor (Car) T cells, not only have the characteristics of strong specific recognition of tu-mor antigens, but also have destruction and high affinity advantages, thus receiving more attention. Although it has played a lot of advantages in anti-tumor, it still has some shortcomings, which needs to be further optimized to improve the safety of its clinical application. In this study, The cell structure and biological function, treatment process, application development and application risk of Car T cells are reviewed, which provide references for further clinical immunotherapy of Car T.

Antagonism of toll-like receptor 2 attenuates the formation and progression of abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disorder with high mortality. Accumulating evidence shows that toll-like receptor 2 (TLR2) plays a critical role in the regulation of wound-repairing process after tissue injury. We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression. In this study, enhanced expression of TLR2 and its ligands were observed in human AAA tissue. Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA. In addition, TLR2-deficient mice also failed to develop AAA. The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling, as indicated by the decreased expression or activity of MMP-2/9, α-SMA, inflammatory cytokines, and transcription factors NF-κB, AP-1 and STAT1/3 in AAA tissue. Mechanistically, blocking TLR2 decreased the expression and interaction of TLR2 and several endogenous ligands, which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA. Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.

Mutation analysis of the PTCH1 gene in a pedigree with nevoid basal cell carcinoma syndrome / 中华皮肤科杂志

Objective To analyze mutations in the PTCH1 gene in a pedigree with nevoid basal cell carcinoma syndrome (NBCCS).Methods Blood samples were collected from a 58-year-old male proband with NBCCS (Ⅱ 5),his brothers (Ⅱ 1 and Ⅱ 3) and son (Ⅲ4),and 50 unrelated healthy human controls.DNA was extracted from these blood samples.PCR and direct DNA sequencing were performed to determine mutation sites in the PTCH1 gene.According to the mutation sites,allele-specific oligonucleotide primers were designed and used to confirm the pathogenic mutations in this pedigree through PCR.Results A nonsense mutation (c.2137C),which leads to the substitution of CAG by TAG with the generation of a premature termination codon (Q714X),was identified in exon 14 in one allele of the PTCH1 gene in the proband and his son,but in none of the healthy human controls.Conclusion The nonsense mutation (c.2137C ＞ T) in the PTCH1 gene may be a specific mutation causing the clinical symptoms in the patient with NBCCS.

Alterations of Treg cells, Th17 cells and some related cytokines in peripheral blood of patients with hand-foot-mouth disease / 中华微生物学和免疫学杂志

Objective To investigate the alterations of Treg cells , Th17 cells and related cyto-kines in peripheral blood of patients during the early stage of hand-foot-mouth disease ( HFMD) .Methods Flow cytometry was performed to analyze the percentages of Treg cells ( CD4+CD25+Foxp3 T cells) and Th17 cells ( CD3+CD8-IL-17+T cells) in peripheral blood samples collected from 49 patients with severe HFMD , 26 patients with common HFMD and 30 healthy children.The levels of IL-6, IL-10, IL-17, IL-23 and TGF-β1 in serum samples were measured by ELISA .Results The percentages of Treg cells , ratios of Treg/Th17 cells, serum levels of TGF-β1 and IL-10 in patients with HFMD were significantly decreased as compared with those of control group (F=5.580, 6.205, 0.000, 0.014, respectively, P0.05).The levels of IL-6 in serum samples from severe disease group were obviously increased as compared with those of common HFMD group and control group (F=7.318, P<0.05).Conclusion The results of this study demonstrated that the levels of Treg , Th17 cells and some related cytokines were varied in peripheral blood of patients dur-ing the early stage of HFMD .Inflammatory responses were enhanced to promote anti-virus activities by sup-pressing Treg cells and stimulating Th17 cells.