Genetic analysis of two children with Coffin-Siris syndrome due to variants of ARID1B gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two children with unexplained psychomotor developmental delay and facial dysmorphisms suggestive of Coffin-Siris syndrome (CSS).@*METHODS@#A boy and a girl suspected for CSS at the 980th Hospital of the People's Liberation Army Joint Service Support Force respectively in July 2019 and January 2021, and seven members from their families, were selected as the study subjects. Clinical data and family history of the children were collected, and detailed physical examination was carried out, in addition with laboratory and related auxiliary examinations. Potential variants and copy number variations (CNVs) were detected by whole exome sequencing (WES) and copy number variation sequencing (CNV-seq).@*RESULTS@#Child 1, an 8-month-old female, had featured microcephaly, atrial septal defect, curving of fifth finger/toe, and low limb muscle tone. Child 2 was a 2.5-year-old male with language delay, social impairment, dense hair but no curving of the fifth fingers. Genetic testing revealed that child 1 had loss of heterozygosity for exons 8 to 21 of the ARID1B gene, which was unreported previously. Family verification showed that both of her parents were of the wild type. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and American Society of Molecular Pathology (AMP), the variant was rated as pathogenic (PVS1+PS2+PM2-supporting). Child 2 was found to harbor a heterozygous c.4263-6 (IVS17) T>G variant of the ARID1B gene. Transcriptome sequencing confirmed that the variant can affect the normal splicing, resulting in retention of a 5 bp sequence in intron 17. Family verification showed that both of his parents were of the wild type. Based on the guidelines from the ACMG, the variant was rated as pathogenic (PS2+PM2-supporting+PP3+PS3).@*CONCLUSION@#WES and RNA-seq have confirmed the diagnosis of CSS in both children. Discovery of the novel variants has expanded the spectrum of pathogenic mutations underlying CSS, and provided a basis for the genetic counseling.

Association between monocyte to lymphocyte ratio and mortality in patients with continuous ambulatory peritoneal dialysis / 中华肾脏病杂志

Objective:To investigate the association of monocyte to lymphocyte ratio (MLR) with all-cause mortality and cardiovascular disease (CVD) mortality in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a retrospective cohort study. The clinical data of 495 incident CAPD patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The optimal cut-off value of baseline MLR was determined by the receiver operating characteristic (ROC) curve for predicting all-cause death in the first year of CAPD, and then the patients were divided into high MLR group and low MLR group. The differences of clinical data and laboratory tests were compared between the two groups. The endpoint events were death (all-cause death and CVD death), conversion to hemodialysis, conversion to kidney transplantation, or follow-up until March 31, 2020. The survival curve was drawn by the Kaplan-Meier method, and the Log-rank test was used to compare the survival difference between the two groups. A Cox regression model was established to analyze the relevant factors of all-cause mortality and CVD mortality in CAPD patients.Results:The study included 495 patients, with age of (43.79±12.16) years and 308 (62.22%) males. The median age of dialysis was 17(10, 30) months. By the end of follow-up, 61(12.32%) of 495 patients had died, 51(10.51%) had been converted to hemodialysis, and 28(5.66%) had been converted to kidney transplantation. Of the 61 patients who died, 36(59.02%) died of cardiovascular events. ROC curve analysis results showed that the optimal cut-off value was 38.24%, so there were 246 cases in the high MLR group (MLR>38.24%) and 249 cases in the low MLR group (MLR≤38.24%). The all-cause mortality rates were 6.83% in the low MLR group and 17.89% in the high MLR group, and the CVD mortality rates were 3.21% in the low MLR group and 11.38% in the high MLR group, respectively. The Kaplan-Meier survival curve showed that the survival rate of the low MLR group was significantly higher than that of the high MLR group (all-cause mortality, Log-rank χ2=18.369, P<0.001; CVD mortality, Log-rank χ2=16.142, P<0.001). Using all-cause death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 89.4% and 79.9%, respectively, with a median survival time of 64 months in the low MLR group. The 1-year, 3-year and 5-year cumulative survival rates were 95.0%, 68.3% and 49.6%, respectively, with a median survival time of 54 months in the high MLR group. Using CVD death as the end event, the 1-year, 3-year and 5-year cumulative survival rates were 99.5%, 95.2% and 91.2%, respectively, with a median survival time of 69 months in the low MLR group. The 1-year, 3-year, and 5-year cumulative survival rates were 97.8%, 78.6%, and 60.8%, respectively, with a median survival time of 60 months in the high MLR group. Multivariate Cox regression analysis showed that MLR was independently associated with all-cause mortality ( HR=2.744, 95% CI 1.484-5.075, P=0.001) and CVD death ( HR=3.249, 95% CI 1.418- 7.443, P=0.005) in CAPD patients. According to the competing risk model analysis, MLR was still independently associated with all-cause mortality and CVD mortality in CAPD patients. Conclusion:MLR is associated with all-cause mortality and CVD mortality in CAPD patients, and can be used as a valuable indicator for judging the prognosis of CAPD patients.

Serum PCT, CRP and CD64 levels in predicting early infection after internal fixation of limb fractures / 中华临床感染病杂志

Objective:To investigate serum C-reactive protein (CRP) , procalcitonin (PCT) and neutrophil CD64 in predicting early infection after internal fixation of limb fractures.Methods:A total of 2 572 patients with limb fractures undergoing internal fixation in Taishun County People’s Hospital from January 2016 to December 2022 were enrolled. Postoperative infection occurred in 121 cases (infected group) and did not occur in 2 451 cases (uninfected group). Serum levels of PCT, CRP and CD64 were tested at admission and d1, d3, d5 and d7 after operation. Repeated measurement analysis of variance was used to compare the serum levels of PCT, CRP and CD64 at different time points between two groups, the receiver operating characteristic curve (ROC) was used to evaluate the predictive value of each index or in combination for early infection after internal fixation of limbs fractures.Results:The early infection rate after internal fixation was 4.70% (121/2 572). The levels of PCT, CRP and CD64 in the infection group began to rise after operation and decreased on d7; there were significant differences in PCT, CRP and CD64 levels between the two groups on d3, d5 and d7 after operation (PCT: Ftime=678.607, Fintergroup=2 218.323, Finteraction=653.150; CRP: Ftime=392.724, Fintergroup=1 812.502, FInteraction =379.577; CD64: Ftime=373.686, Fintergroup=4 817.438, Finteraction=528.353, all P< 0.001) . The area under the ROC curve of combined detection of PCT, CPR, and CD64 for predicting early infection was 0.856; the sensitivity and specificity of combined detection were 69.2% and 94.7%, respectively. The combined detection of three indicators showed better prediction values than PCT, CRP and CD64 alone ( Z=6.176, 3.838 and 2.431, P<0.01 or <0.05), and also better than combined detection of PCT and CRP ( Z=2.875, P=0.019). Conclusions:The combined detection of CD64, PCT and CRP is of value in prediction of postoperative infection after internal fixation of limb fractures, which is worthy of clinical application.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Effects of music therapy combined with fluoxetine on depression and activities of daily living in patients with post-stroke depression / 西安交通大学学报(医学版)

【Objective】 To observe the clinical therapeutic effects of music therapy combined with fluoxetine on post stroke depression (PSD). 【Methods】 One hundred and twelve patients with PSD were randomly divided into control group (56 cases) and treatment group (56 cases). The control group took fluoxetine 20 mg/d, while the treatment group received music therapy additionally. Hamilton Depression Scale (HAMD) was used to evaluate depression level; Barthel Index (BI) was used to evaluate the subjects’ daily living before and after treatment. 【Results】 After 4 weeks’ treatment, the HAMD scores were decreased while BI scores were increased after music therapy in the treatment group compared with control group (P<0.01). 【Conclusion】 Fluoxetine combined with music therapy can improve depression symptoms and the capacity of daily activities of PSD patients.

Clinical significance and expression of inhibin βB in nasopharyngeal carcinoma and lung adenocarcinoma / 中国医师杂志

Objective:To investigate the expression of inhibin β B (INHBB) in nasopharyngeal carcinoma (NPC) and lung adenocarcinoma (LUAD) and its relationship with clinicopathological features.Methods:Paraffin-embedded tissue specimens of 39 patients with NPC and 16 patients with chronic nasopharyngitis diagnosed by biopsy, and 30 patients with LUAD after surgical resection collected in Brain Hospital of Hunan Province (the Second People′s Hospital of Hunan Province) were analyzed retrospectively. The expression of INHBB in NPC and LUAD was detected by immunohistochemical streptavidin-perosidase (SP) method and the relationship of INHBB expression level with clinicopathological indicators was analyzed.Results:The expression of INHBB in NPC was lower than that in chronic nasopharyngitis (51.28% vs 81.25%, P=0.039), and the expression of INHBB was related to lymph node metastasis ( P=0.026) and clinical stage ( P=0.039); On the contrary, the expression level of INHBB in LUAD was significantly higher than that in adjacent tissues (86.67% vs 23.33%, P<0.001). The expression level of INHBB in patients with LUAD was only related to clinical stage ( P=0.048). Conclusions:The expression of INHBB might play an important role in the development and progression of NPC and LUAD, and it was expected to be a novel diagnostic biomarker.

The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation

The immune checkpoint blockade (ICB) targeting on PD-1/PD-L1 has shown remarkable promise in treating cancers. However, the low response rate and frequently observed severe side effects limit its broad benefits. It is partially due to less understanding of the biological regulation of PD-L1. Here, we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular presentation. In PD-L1 and PD-L2 highly expressed cancer cells, a new TAD (topologically associating domain) (chr9: 5,400,000-5,600,000) around CD274 and CD273 was discovered, which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and PD-L2. The re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of PD-L1. After transcription, the PD-L1 is tightly regulated by miRNAs and RNA-binding proteins via the long 3'UTR. At translational level, PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and ubiquitination. In addition, PD-L1 can be secreted via exosome to systematically inhibit immune response. Therefore, fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.

Famous traditional Mongolian medicine Xieriga-4 (Turmeric-4) decoction: A review / 中草药·英文版

Xieriga-4 Decoction, composed of dried rhizomes of Curcumae longae, barks of Phellodendron chinense or Phellodendron amurense, fruits of Cardenia jasminoides, and fruits of Tribulus terrestris, is a famous prescription of traditional Mongolian medicine for the treatment of urinary system diseases such as frequent urination, urgent urination, urine occlusion, hematuria, bladder irritation and pain. This paper reviewed Xieriga-4 Decoction from the aspects of historical description, prescription principle, chemical components, pharmacology, clinical application and quality control.

Effect of Fluoxetine on Metabolic Diversity of Intestinal Microbiota in Rats With Depression / 胃肠病学

Background: Studies have shown that intestinal microbiota is closely related to the occurrence and development of depression, however, the regulatory mechanism of the classic antidepressant fluoxetine on intestinal microbiota is still unclear. Aims: To investigate the mechanism of fluoxetine in regulating intestinal microbiota structure and metabolic diversity in rats with depression. Methods: Thirty SD rats were randomly divided into blank group, model group and fluoxetine group. Depression rat model was established by chronic unpredictable mild stress (CUMS) combined with solitary care. Fluoxetine hydrochloride dispersible tablets 3.17 mg•kg

Correlation between nutritional status and mental sub-health among Chinese adolescents / 中国学校卫生

Objective@#To explore the correlation between different nutritional status and mental sub-health of Chinese adolescents, and provide reference for improving the physical and mental health of Chinese adolescents.@*Methods@#A total of 16 545 adolescents (13-22 years old) were selected by random overall sampling method in six major administrative regions in China.The psychological part of the Multidimensional Sub-health Questionnaire of Adolescents (MSQA) was used for mental sub-health test.Chi-square test and Logistic regression analysis were used to analyze and compare the relationship between different nutritional status and mental sub-health.@*Results@#The overall detection rate of mental sub-health status in the adolescents with normal BMI group was 18.5%, while those in the lean, overweight and obese groups were 22.3%, 38.7%, and 44.7%, respectively, which were significantly different from those in the normal BMI group(χ2=478.68，P<0.05).After adjusted for gender and age, the Logistic regression model showed that compared with those with normal BMI, those who were thin (OR=1.19, 95%CI=1.09-1.30), overweight (OR=2.76, 95%CI=2.47-3.09) and obese(OR=3.43, 95%CI=2.83-4.15) had increased risk of mental sub-health.@*Conclusion@#The nutritional status of Chinese adolescents in significantly related to mental sub-heatlh,hose who are underweight, overweight and obese have significantly higher risks of mental sub-health than those who are normal.Improvement of nutritional status of adolescents is beneficial to healthy adolescent development.

ADR Signal Mining of Rivaroxaban Based on FDA Adverse Event Reporting Database / 中国药房

OBJECTIVE：To excavate the ADR signals of rivaroxaban and provide reference for its safe and rational use in clinic. METHODS ：Based on FDA adverse event reporting system （FAERS），the ADRs of rivaroxaban reported from September 2008 to December 2020 in FDA ’s Open Data Program were mined using ratio of reports to odds （ROR）and proportional report ratio （PRR）. The related ADRs were analyzed ，and the corresponding system organ classification （SOC）was mapped. At the same time，the basic information such as gender ，age and indications of the patients were statistically reported. RESULTS & CONCLUSIONS：Among 9 373 236 ADR reports extracted ，102 027 ADR reports with rivaroxaban as concomitant and suspected drug were obtained ；883 ADR signals were mined ，involving 27 systems. Among 102 027 reports，the proportion of female patients （41 294 cases，40.47％）was similar to that of male patients （41 071 cases，40.26％）. The patients were mainly ＞50 to 75 years old（29 261 cases，28.68％）and ＞75 years old （21 470 cases，21.04％）. The reporting year was mainly in 2018（18 446 cases， 18.08％）；main reporting country was the United States （75 390 cases，73.89％）；there were 35 046 cases（34.35％）of severe ADR reports ，mainly involving hospital or prolonged hospital stay. The SOC of rivaroxaban ADR singal mainly focused on diseases of the blood and lymphatic system ，vascular diseases ，various types of examination and nervous system diseases. Among top 20 preferred terms of ADRs with the highest frequency ，except for pulmonary embolism ，acute kidney injury and atrial fibrillation ，the rest were mainly bleeding related ADRs ，of which intracranial hemorrhage was the more seriou s ADR. Intracranial hemorrhage may occur when rivaroxaban is used for the prevention of atrial fibrillation and cerebrovascular accidents ， and pulmonary embolism may occur when rivaroxaban is used for the prevention of pulmonary embolism ，（deep）venous thrombosis and thrombosis. Great importance should be paid on it.

Effect of remifentanil on MAPK signaling pathway during intestinal epithelial cell apoptosis induced by intestinal ischemia-reperfusion in rats / 中华麻醉学杂志

Objective:To evaluate the effect of remifentanil on mitogen-activated protein kinase (MAPK) signaling pathway during intestinal epithelial cell apoptosis induced by intestinal ischemia-reperfusion (I/R) in rats.Methods:Thirty-six clean grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, aged 2 months, were divided into 3 groups ( n=12 each) by a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group) and remifentanil group (R group). Intestinal I/R was produced by occlusion of superior mesenteric artery for 1 h followed by reperfusion in anesthetized rats.At 30 min before ischemia, 0.2 μg·kg -1·min -1 of remifentanil was infused intravenously for 5 min , followed by infusion of normal saline for 5 min, repeating for 3 cycles in group R. At 2 h of reperfusion, blood samples were collected from right ventricle to measure the concentration of diamine oxidase (DAO). The animals were then sacrificed and the intestinal tissues were obtained for examination of pathological changes and scored according to Chiu, for calculation of intestinal epithelial cell apoptosis rate (by TUNEL), for determination of the expression of phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated p38 MAPK (p-p38 MAPK), cleaved caspase-3 and nuclear factor kappa B p65 (NF-κB p65) in nucleoprotein and for calculation of p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio in the intestinal tissues. Results:Compared with group Sham, Chiu′s scores, serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues were significantly increased in group I/R, and Chiu′s scores was increased ( P<0.05), and no significant change was found in serum DAO concentration, apoptosis rate, p-ERK/ERK ratio, p-JNK/JNK ratio, p-p38 MAPK/p38 MAPK ratio and the expression of cleaved caspase-3 and NF-κB p65 in the intestinal tissues in group R ( P>0.05). Compared with group I/R, Chiu′s scores, apoptosis rate, serum DAO concentration, p-ERK/ERK ratio and expression of cleaved caspase-3 and NF-κB p65 were significantly decreased in group R ( P<0.05). Conclusion:The mechanism by which remifentanil inhibits intestinal epithelial cell apoptosis induced by intestinal I/R is related to promoting activation of ERK in rats.

Influencing factors of myopia among primary and secondary school students in Shenzhen / 中国学校卫生

Objective@#To investigate the associated factors of myopia among primary and secondary school students in Shenzhen, and to provide reference for the prevention and control of myopia.@*Methods@#By stratified cluster sampling, 3 073 students of 14 schools including primary,junior,regular and vocational senior schools from two districts in Shenzhen were selected and investigated.@*Results@#For primary school students, the time of using computer for 2-<3 hours per day (OR=2.23，95%CI=1.19-4.20) , and no physical education class(2 sections per week OR=0.34, 95%CI=0.13-0.91; 4 sections per week OR=0.23, 95%CI=0.08-0.62; 5 sections or more per week OR=0.33, 95%CI=0.11-0.97) were positively associated with myopia. Teachers finishing class on time at break (occasionally delaying OR=1.99, 95%CI=1.51-2.63; frequently delaying OR=2.07, 95%CI=1.29-3.30), taking 0.5-1 hour break when using eyes at close range (1-<2 hours OR=1.33，95%CI=1.03-1.70; ≥3 hours OR=1.87, 95%CI=1.17-3.00), no parents with myopia(one parent with myopia OR=1.69, 95%CI=1.32-2.17; two parents with myopia OR=2.13, 95%CI=1.50-3.02) were negatively associated with myopia. For junior high school students, without parents with myopia (one parent with myopia OR=3.27, 95%CI=2.17-4.94; two parents with myopia OR=5.38, 95%CI=2.78-10.42) was the protective factor of myopia. For senior high school students, male (female OR=1.52, 95%CI=1.07-2.14), doing eye exercises twice a day in school (OR=0.41, 95%CI=0.23-0.75), and accumulating outdoor activities for ≥2 hours a day (OR=0.70, 95%CI=0.49-1.00) were negatively associated with myopia.@*Conclusion@#There are different risk factors for myopia among different students in Shenzhen. Students with high risk factors are the key objects of prevention and control.

Effects of Sacubitril/Valsartan on biochemical indicators and on left ventricular structure in NYHA Ⅳ heart failure with reduced ejection fraction patients / 中华老年医学杂志

Objective To investigate the effects of Sacubitril/Valsartan on amino terminal probrain natriuretic peptide (NT-proBNP),high sensitivity C-reactive protein (hs-CRP),soluble suppression of tumorigenicity 2(sST2)levels and on left ventricular(LV)structure in NYHA Ⅳ heart failure with reduced ejection fraction(HFrEF) patients.Methods A total of 67 HFrEF patients with NYHA Ⅳ were randomly divided into the control group (n =30)receiving conventional medical treatment,and the observation group(n=32)receiving Sacubitril/Valsartan instead of ACEI(or ARB if ACEI induced cough) in conventional medical treatment.NT-proBNP levels were determined by fluorescer-enhanced chemiluminescence.hs CRP levels were detected by latecx enhanced immunoturbidimetric assay.sST2 levels were determined by enzyme-linked immunosorbent assay (ELISA).The modified Simpson method was used to detect left ventricular end-diastolic diameter (LVEDD),LV posterior wall(LVPW)and LV ejection fraction(LVEF).Two groups of patients were treated and followed-up for 6 months.Results Clinical efficacy was better in the observation group than in the control group(effective rate,20 cases or 61.3％ vs.8 cases or 26.7％,P＜0.05).As compared with the control group,the observation group of patients had an increased LVEF[(46.7±9.2) ％ vs.(41.8±8.0)％,P＜0.05]and a decreased LVEDD[(52.6±6.7)mm vs.(58.8±7.5)mm,P＜0.05].After vs.before treatment,NT-proBNP,hs-CRP and sST2 levels were decreased in both control and observation groups [(1 427 ± 219) μg/L vs.(2 615 ± 273)μg/L,(1.14 ± 1.02) mg/L vs.(1.55±1.38)mg/L,(0.30±0.12)μg/L vs.(0.41±0.10)μg/L,all P＜0.05],and the decrements were much more in the observation group than in the control group (P＜0.05).The annual accumulated frequence and duration of hospitalization were less in the observation group than in the control group[(0.8±0.6)times vs.(1.8±1.0) times,(10.2±5.8)d vs.(16.5±7.2)d,P＜0.05].The maintenance dose of tolasemide was lower in the observation group than in the control group [(15.2±8.4)mg vs.(20.6±10.8)mg,P＜0.05].Conclusions Sacubitril/valsartan therapy is safe and effective and it can reduce hs-CRP and sST2 levels and improve the ventricular remodeling in HFrEF patients of HYHA Ⅳ.

Effect of comfrey cream combined with NB-UVB on skin barrier function and immune function in the patients with psoriasis vulgaris / 国际中医中药杂志

Objective@#To investigate the effects of comfrey cream combined with narrow-band UVB (NB-UVB) on skin barrier function and immune function in the patients with psoriasis vulgaris.@*Methods@#A total of 100 patients with psoriasis vulgaris admitted from March 2016 to June 2017 were enrolled in the study. They were randomly divided into observation group (Purple Cream + NB-UVB) and control group (NB- UVB), 50 cases in each group. Psoriasis lesion area and severity index (PASI) and degree of pruritus were evaluated before treatment, after 2 weeks and 4 weeks of treatment. The skin barrier function and immune related indicators were compared between the two groups before and after the treatment.@*Results@#After treatment, the PASI score and pruritus score of the observation group and the control group showed a decreasing trend, and the observation group decreased more significantly. The interaction between the two groups at different time points, and between groups and at different time points were statistically significant (t values were 3.462, 2.833, P<0.05). After treatment, the water content of the stratum corneum (54.34% ± 5.04% vs. 49.03% ± 5.26%, t=5.154) and the sebum content (143.03 ± 11.60 μg/cm2 vs. 130.79 ± 14.54 μg/cm2, t=4.653) in the observation group were higher than those in the control group, and the transepidermal water loss (TEWL) [15.87 ± 4.22 g/(h•m2) vs. 19.87 ± 3.06 g/(h•m2), t=5.426] in the observation group was lower than that in the control group (P<0.05). The CD4+ (42.06% ± 4.68% vs. 33.01% ± 3.07%, t=11.433), CD4+/CD8+ (20.89 ± 3.44 vs. 26.03 ± 3.44, t=8.209) in observation group and control group were increased after treament, while CD8+(1.89% ± 0.29% vs. 1.43% ± 0.27%, t=7.471) was decreased, the observation group was superior to the control group (P<0.05).@*Conclusions@#Treatment of vulgaris vulgaris with comfrey cream combined with NB-UVB can improve symptoms and improve skin barrier function and immune function.

Analysis of factors influencing disease severity in 2 620 children with atopic dermatitis / 中华皮肤科杂志

Objective@#To investigate factors influencing disease severity in children of Han nationality with atopic dermatitis (AD) in China, and to provide scientific evidences for prevention and treatment of AD in children.@*Methods@#From November 2005 to May 2015, data were collected from AD children aged 0-12 years in Department of Dermatology, The First Affiliated Hospital of Anhui Medical University and AD sample collection collaboration network in China. Statistical analysis was carried out with SPSS16.0 software by using univariate and multivariate ordinal logistic regression analysis to investigate factors influencing the severity of AD.@*Results@#A total of 2 620 children with AD were enrolled into the study, including 230 (8.8%) with mild AD, 1 379 (52.6%) with moderate AD and 1 011 (38.6%) with severe AD. As univariate analysis showed, factors influencing the severity of AD included region, early onset, itching during sweating, xeroderma, ichthyosis, palmar hyperlinearity, lichen pilaris, orbital darkening, scalp dermatitis and infra-auricular fissure (all P<0.01) . There were no significant differences in the severity of AD between different genders, patients with and without personal or family atopic history, or between patients with and without a high serum IgE level (all P > 0.05) . Multivariate ordinal logistic regression analysis showed that southern region (OR = 2.10, 95% CI: 1.76 - 2.51) , early onset (OR = 1.32, 95% CI: 1.01 - 1.71) , itching during sweating (OR = 1.70, 95% CI: 1.42 - 2.02) , xeroderma (OR = 2.57, 95% CI: 2.10 - 3.15) , ichthyosis (OR = 1.49, 95% CI: 1.19 - 1.87) , palmar hyperlinearity (OR = 2.03, 95% CI: 1.61 - 2.57) , lichen pilaris (OR = 1.44, 95% CI: 1.17 - 1.78) , orbital darkening (OR = 1.53, 95% CI: 1.24 - 1.89) , scalp dermatitis (OR = 2.38, 95% CI: 2.01 - 2.82) and infra-auricular fissure (OR = 1.55, 95% CI: 1.31 - 1.85) were positively correlated with the severity of AD (all P<0.05) .@*Conclusion@#The severity of AD is associated with patients′ region, early onset, itching during sweating, xeroderma, and other concomitant symptoms.

Advancement of targeted agents in the treatment of anaplastic thyroid carcinoma / 国际肿瘤学杂志

Anaplastic thyroid carcinoma (ATC) is very rare and aggressive in humans,and its survival time is most often expressed in weeks or months.For now,there is no standard treatment for long-term survival,even if the multidisciplinary approach could prolong survival in some patients.The development of oncomolecular biology promotes the understanding about the pathogenesis of ATC from genetic level,and then providing a theoretical basis for targeted therapy.Some targeted drugs have been approved for the treatment of refractory advanced differentiated thyroid cancer,in the meantime,the clinical trials of targeted therapy bring new hope for ATC patients.

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. To address this, a CT-26 colon cancer xenograft model was established in mice since this cell line is insensitive to SHP099. Consequently, SHP099 minimally affected CT-26 tumor growth in immuno-deficient nude mice, but significantly decreased the tumor burden in CT-26 tumor-bearing mice with intact immune system. SHP099 augmented anti-tumor immunity, as shown by the elevated proportion of CD8IFN- T cells and the upregulation of cytotoxic T-cell related genes including , which decreased the tumor load. In addition, tumor growth in mice with SHP2-deficient T-cells was markedly slowed down because of enhanced anti-tumor responses. Finally, the combination of SHP099 and anti-PD-1 antibody showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in two colon cancer xenograft models, indicating that these agents complement each other. Our study suggests that SHP2 inhibitor SHP099 is a promising candidate drug for cancer immunotherapy.

Analysis of factors influencing disease severity in 2 620 children with atopic dermatitis / 中华皮肤科杂志

Objective To investigate factors influencing disease severity in children of Han nationality with atopic dermatitis (AD) in China,and to provide scientific evidences for prevention andtreatment of AD in children.Methods From November 2005 to May 2015,data were collected from AD children aged 0-12 years in Department of Dermatology,The First Affiliated Hospital of Anhui Medical University and AD sample collection collaboration network in China.Statistical analysis was carried out with SPSS16.0 software by using univariate and multivariate ordinal logistic regression analysis to investigate factors influencing the severity of AD.Results A total of 2 620 children with AD were enrolled into the study,including 230 (8.8％) with mild AD,1 379 (52.6％) with moderate AD and 1 011 (38.6％) with severe AD.As univariate analysis showed,factors influencing the severity of AD included region,early onset,itching during sweating,xeroderma,ichthyosis,palmar hyperlinearity,lichen pilaris,orbital darkening,scalp dermatitis and infra-auricular fissure (all P ＜ O.O1).There were no significant differences in the severity of AD between different genders,patients with and without personal or family atopic history,or between patients with and without a high serum IgE level (all P ＞ 0.05).Multivariate ordinal logistic regression analysis showed that southern region (OR =2.10,95％ CI:1.76-2.51),early onset (OR =1.32,95％ CI:1.01-1.71),itching during sweating (OR =1.70,95％ CI:1.42-2.02),xeroderma (OR =2.57,95％ CI:2.10-3.15),ichthyosis (OR =1.49,95％ CI:1.19-1.87),palmar hyperlinearity (OR =2.03,95％ CI:1.61-2.57),lichen pilaris (OR =1.44,95％ CI:1.17-1.78),orbital darkening (OR =1.53,95％ CI:1.24-1.89),scalp dermatitis (OR =2.38,95％ CI:2.01-2.82) and infra-auricular fissure (OR =1.55,95％ CI:1.31-1.85) were positively correlated with the severity of AD (all P ＜ 0.05).Conclusion The severity of AD is associated with patients' region,early onset,itching during sweating,xeroderma,and other concomitant symptoms.

Effect of comfrey cream combined with NB-UVB on skin barrier function and immune function in the patients with psoriasis vulgaris / 国际中医中药杂志

Objective To investigate the effects of comfrey cream combined with narrow-band UVB (NB-UVB) on skin barrier function and immune function in the patients with psoriasis vulgaris. Methods A total of 100 patients with psoriasis vulgaris admitted from March 2016 to June 2017 were enrolled in the study. They were randomly divided into observation group (Purple Cream + NB-UVB) and control group (NB- UVB), 50 cases in each group. Psoriasis lesion area and severity index (PASI) and degree of pruritus were evaluated before treatment, after 2 weeks and 4 weeks of treatment. The skin barrier function and immune related indicators were compared between the two groups before and after the treatment. Results After treatment, the PASI score and pruritus score of the observation group and the control group showed a decreasing trend, and the observation group decreased more significantly. The interaction between the two groups at different time points, and between groups and at different time points were statistically significant (t values were 3.462, 2.833, P<0.05). After treatment, the water content of the stratum corneum (54.34% ±5.04% vs. 49.03% ±5.26%, t=5.154) and the sebum content (143.03 ±11.60 μg/cm2 vs. 130.79 ±14.54 μg/cm2, t=4.653) in the observation group were higher than those in the control group, and the transepidermal water loss (TEWL) [15.87 ± 4.22 g/(h?m2) vs. 19.87 ± 3.06 g/(h?m2), t=5.426] in the observation group was lower than that in the control group (P<0.05). The CD4+(42.06% ±4.68% vs. 33.01% ±3.07%, t=11.433), CD4+/CD8+(20.89 ±3.44 vs. 26.03 ± 3.44, t=8.209) in observation group and control group were increased after treament, while CD8+(1.89% ± 0.29% vs. 1.43% ± 0.27%, t=7.471) was decreased, the observation group was superior to the control group (P<0.05). Conclusions Treatment of vulgaris vulgaris with comfrey cream combined with NB-UVB can improve symptoms and improve skin barrier function and immune function.