Objective To evaluate safety and efficacy of a fractional microneedle radiofrequency device in the treatment of axillary osmidrosis.Methods A total of 24 patients with moderate to severe axillary osmidrosis were enrolled from Department of Dermatology of Peking Union Medical College Hospital between June 2015 and June 2016,and treated with the Body TiteTM fractional microneedle radiofrequency device for 1 session.Visual analogue scale (VAS) was used to evaluate the intensity of axillary odor in patients,36-item short-form health survey (SF-36) to assess health-related quality of life (HRQoL),and axillary skin tissues were resected for histopathological examination before and after the treatment.Results VAS showed that 22 of 24 patients achieved persistent remission for more than 12 weeks,and rates of decrease in odor score ranged from 50％ to 100％.However,1 patient experienced recurrence at 12 weeks after the treatment,and another 1 patient did not achieve clinical remission.SF-36 revealed that scores of social functioning (SF),role-emotional (RE) and mental health (MH) scales were all significantly increased after the treatment [M (P0-P100):100.00 (62.00-112.50),100.00 (33.30-110.00),68.00 (48.00-80.00),respectively] compared with those before the treatment [77.50 (62.50-100.00),66.67 (33.30-100.00),55.00 (48.88-72.00),respectively,all P ＜ 0.05].Histopathological examination showed obvious degeneration and necrosis of sweat gland cells in 22 cases,and epidermal damages in 2 patients after the treatment.Unilateral upper-limb pain occurred in 1 case,and small-area burn-like skin changes were observed in 2 cases after the treatment.The postoperative recovery time ranged from 7 to 14 days.Conclusion The fractional microneedle radiofrequency device has shown high clinical response rate,good safety,and favorable application prospects in the treatment of axillary osmidrosis.

Objective:To investigate clinicopathological features of 4 cases of intravascular large B-cell lymphoma (IVLBCL) .Methods:Clinical and pathological data were collected from 4 patients with histopathologically confirmed IVLBCL in Department of Dermatology, Peking Union Medical College Hospital from January 2020 to November 2020, and retrospectively analyzed.Results:The 4 patients were aged 57 - 76 years, including 2 males and 2 females. Of the 4 patients, all had neurological symptoms, 3 had fever, 3 exhibited impaired exercise tolerance and suffocation, and 3 exhibited pitting edema of the body. Case 1 presented with a cherry hemangioma-like papule measuring 0.2 cm in diameter on the back, and case 2 with telangiectasia on the left breast and upper abdomen. Six skin samples were taken from the 4 patients for histopathological and immunohistochemical studies, and tumor cells were found in 1 cherry hemangioma-like lesion and 1 lesion of telangiectasia, as well as in 2 of 4 normal skin samples. Histopathological findings mainly were dilated dermal blood vessels filled with large atypical mononuclear cells, and the atypical mononuclear cells were positive for CD20 immunohistochemically.Conclusion:For those patients with suspected IVLBCL, hemangioma-like and telangiectasia lesions tend to show characteristic histopathological and immunohistochemical findings, and a biopsy of normal skin can facilitate early diagnosis of IVLBCL.

Adolescent ; Adult ; Aged ; Blood Banks ; legislation & jurisprudence ; Blood Donors ; legislation & jurisprudence ; Child ; Female ; Hepatitis C ; epidemiology ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective To evaluate the effect ofmicroRNA-143 (miR-143) on interleukin (IL)-13-induced expression of kallikrein 7 (KLK7) in primary normal human epidermal keratinocytes (NHEKs).Methods Some NHEKs at exponential growth phase were divided into 4 groups to be treated with recombinant human IL-13 at different concentrations of 0,2,10 and 50 μg/L respectively for 24 hours,and some NHEKs were treated with 50 μg/L IL-13 for 0,6,12,24 and 48 hours separately.After the treatment,NHEKs were collected,and total RNA was extracted.Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of KLK7.Some other NHEKs were divided into another 4 groups:NHEK group (blank control group) receiving no treatment,IL-13 group treated with 50 μg/L IL-13,miR-NC group transfected with miRNA mimics negative control followed by the treatment with 50 μg/L IL-13,and miR-143 group transfected with miR-143 mimics followed by the treatment with 50 μg/L IL-13.After 24-hour treatment with IL-13,real-time fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of KLK7 respectively in the above groups.Results After 24-hour treatment with IL-13 at concentrations of 0,2,10 and 50 μg/L,the mRNA expression of KLK7 in NHEKs was 1.00 ± 0.12,0.89 ± 0.04,1.15 ± 0.09 and 1.70 ± 0.10 respectively,and significantly increased along with the increase of IL-13 concentrations (F =92.48,P ＜ 0.05).After 0-,6-,12-,24-and 48-hour treatment with 50 μg/L IL-13,the mRNA expression of KLK7 in NHEKs was 1.00 ± 0.05,1.05 ± 0.12,1.71 ± 0.20,1.97 ± 0.19 and 2.48 ± 0.13 respectively,and significantly increased over time (F =206.44,P ＜ 0.05).Compared with the miR-NC group,the miR-143 group showed significantly decreased mRNA and protein expression of KLK7 (t =6.76,4.23 respectively,both P ＜ 0.05).Conclusion In NHEKs,IL-13 can up-regulate the expression of KLK7,likely by the regulation of miR-143.

Objective To analyze the disease constitution,accuracy of clinical and pathological diagnoses of skin biopsy samples in Peking Union Medical College Hospital.Methods A total of 29987 patients subjected to skin biopsy were collected from Department of Dermatology,Peking Union Medical College Hospital from June 2010 to November 2018,and clinical and histopathological diagnoses of these skin biopsy samples were analyzed retrospectively.Results According to the results of histopathological diagnosis,confirmed diagnoses of these patients could be classified into 33 categories and 242 kinds.Common disease categories included epidermal tumors (2931 cases,9.77％),connective tissue diseases (2809 cases,9.37％),melanocytic tumors (2078 cases,6.93％),erythematous scaly pustular dermatoses (1376 cases,4.59％),lichenoid dermatoses (1291cases,4.31％),allergic or eczematous skin diseases (1282 cases,4.28％)and infectious skin diseases (1156 cases,3.86％).Common skin diseases included scleroderma (1887 cases,6.29％),pigmented nevus (1755 cases,5.85％),seborrheic keratosis (1136 cases,3.79％),eczema (1089 cases,3.63％),psoriasis (881 cases,2.94％),lichen planus (867 cases,2.89％),lupus erythematosus (638 cases,2.13％),pemphigus (549 cases,1.83％),and basal cell carcinoma (501 cases,1.67％).Poor consistency was observed between clinical diagnosis and histopathological diagnosis of lichen planus,bullous pemphigoid,granuloma annulare and hypereosinophilic dermatitis.Conclusions Common disease categories of the skin biopsy samples in Peking Union Medical College Hospital were epidermal tumors,connective tissue diseases,melanocytic tumors,erythematous scaly pustular dermatoses,lichenoid dermatoses,and allergic or eczematous skin diseases.Poor consistency was observed between clinical and pathological diagnosis in some skin diseases,and understanding of these diseases should be improved.

Objective:To analyze the genetic etiology and prognosis in fetuses with increased nuchal translucency (NT) in order to assist in the clinical prenatal genetic counseling and diagnosis.Methods:This study retrospectively enrolled 1 658 cases of singleton pregnancy (<35 years old) receiving invasive prenatal diagnosis, including karyotype analysis and/or chromosome microarray analysis or copy number variation (CNV) sequencing, due to NT value ≥2.5 mm in the first trimester in Henan Provincial People's Hospital from August 2014 to December 2021. They were divided into different groups according to the thickness of NT (≥2.5-<3.0, ≥3.0-<3.5, ≥3.5-<4.5, ≥4.5-<5.5, ≥5.5-<6.5 and ≥6.5 mm groups) and abnormal ultrasound findings (isolated increased NT group, increased NT complicated by soft markers/non-severe structural abnormality group and increased NT complicated by severe structural abnormality group). The results of invasive prenatal diagnosis and pregnancy outcomes were compared between different groups using Chi-square test and trend Chi-square test. Results:The detection rates of numerical abnormalities of chromosomes were 15.8% (262/1 658) and 17.6% (252/1 431) when the NT thickness cut-off value were 2.5 mm or 3.0 mm, respectively. Overall, the detection rate of numerical abnormalities of chromosomes increased with thickness of NT ( χ2trend=180.75, P<0.001), ranging from 6.6% (44/671) in the NT≥2.5-<3.5 mm group to 45.6% (113/248) in the NT≥5.5 mm group. The incidence of pathogenic/likely pathogenic CNV(P/LP CNV) did not increased with NT thickness ( χ2trend=3.26, P=0.071), and the highest detection rate was observed in the NT≥4.5-<5.5 mm group (9.0%, 19/211). The detection rate of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥2.5-<3.0 mm group and NT≥3.0-<3.5 mm group were 5.3% (10/188) and 9.6% (36/375), respectively, however, the difference was not statistically significant ( χ2=3.06, P=0.080). The detection rates of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥3.5-<4.5 mm group and NT≥2.5-<3.0 mm complicated by soft markers/ non-severe structural abnormality group were 12.7% (52/410) and 24.1% (7/29), respectively, and the risk were 2.6 times (95% CI: 1.3-5.2) and 5.7 times (95% CI: 2.0-16.4) of the isolated NT≥2.5-<3.0 mm group, respectively. The pregnancy termination rate increased with the NT thickness ( χ2trend=304.42, P<0.001), ranging from 10.8% (23/212) in the NT≥2.5-<3.0 mm group to 90.7% (117/129) in the NT≥6.5 mm group. After exclusion of the pregnancies terminated due to numerical abnormalities of chromosomes and P/LP CNV, 87.6% (862/984) of the fetus with increased NT were born alive. Conclusions:The detection rate of numerical abnormalities of chromosomes increases with the thickness of NT. Invasive prenatal diagnosis is required for non-advance aged singleton pregnant women when fetuses present with isolated NT≥2.5 mm with or without soft markers/structural abnormalities.

OBJECTIVE: To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening. METHODS: 7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up. RESULTS: Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ ²=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ ²=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ ²=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. CONCLUSION Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.
Amniotic Fluid ; Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Genomics ; Humans ; Pregnancy ; Pregnancy Trimester, Second ; Pregnant Women ; Prenatal Diagnosis/methods* ; Technology

Objective:To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE 3) levels and XLI. Methods:A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE 3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results:Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE 3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant ( Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions:The decrease levels of uE 3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE 3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

[摘 要] 目的：以磷酸化蛋白质组学技术分析抗菌肽merecidin处理人肺腺癌A549细胞后细胞内磷酸化蛋白质表达的差异，探究merecidin对肺腺癌A549细胞蛋白质活性、功能的影响以及涉及的信号通路。方法：采用9 μmol/L merecidin处理肺腺癌A549细胞6 h，收集并提取总蛋白，SDS-PAGE检验全蛋白提取效果，加入胰酶来对蛋白质进行酶解。酶解所获肽段用TMT标记、采用HPLC分级分离、经IMAC磷酸化修饰富集以及液相色谱-质谱联用（HPLC-MS/MS）分离肽段。使用localization probability>0.75的标准对鉴定数据进行过滤，利用GO（Gene Ontology）数据库、KEGG（KyotoEncyclopedia of Genes and Genomes）数据库和STRING数据库对磷酸化蛋白组学数据进行分析。结果：SDS-PAGE 结果显示，经9 μmol/L merecidin处理后的A549细胞全蛋白分离效果清晰、无明显降解，且实验组与对照组条带差异明显；质谱共鉴定出位于3 089个蛋白上的10 320个磷酸化修饰位点，以|Fold change|>或<1.5且P<0.05为阈值从中筛选出差异明显的753个蛋白质及其1 172个磷酸化位点。蛋白质功能富集显示，磷酸化水平显著变化的蛋白质功能主要集中在蛋白质分子结合、代谢活性、分子功能调节、细胞进程、生物功能调节等方面；整合通路生物信息学分析结果显示，差异蛋白与Ras、PI3K/AKT、mTOR、AMPK等多条通路相关联；经过COG数据库筛选，发现差异性磷酸化蛋白主要集中在细胞信号转导、RNA转录、翻译后加工和修饰、核糖体合成蛋白质、细胞骨架蛋白形成及细胞内的物质转运和分泌、囊泡运输等多个方面；蛋白质互相作用层面分析结果显示，merecidin处理后的A549细胞中形成以MAPK1、RPL23A、SRSF3H、NCBP1等为关键蛋白的相互作用网，其中ATG2B、ULK1等蛋白显著上调，MAPK1、AKT1等蛋白显著下调。结论：磷酸化蛋白组学分析结果显示，抗菌肽merecidin可能通过MAPK、RPL23A、SRSF3H和AKT1等关键蛋白质在多方面生物功能和多条信号通路中发挥作用，促进肺腺癌A549细胞凋亡和自噬，从而抑制细胞的增殖。

Objective: To prepare oxymatrine phospholipid complex solid lipid nanoparticles(OMT-PC-SLN) lyophilized powder and evaluate its pharmaceutical properties. Method: Pseudo-ternary phase diagram was employed to optimize the formula of microemulsion;single factor experiments were adopted to optimize the formulation process of OMT-PC-SLN lyophilized powder with encapsulation efficiency as index;the morphology of this preparation was observed by transmission electron microscope(TEM).The particle size was measured by particle size analyzer and the in vitro release performance of OMT-PC-SLN lyophilized powder was examined. Result: Optimal formulation process was as following:taking soybean phospholipid and polyethylene glycol 15-hydroxystearate(Kolliphor HS 15) as the emulsifier,ethanol as co-emulsifier,ratio of emulsifier to co-emulsifier(K_m)=3:2,oil phase:(emulsifier+co-emulsifier)=1:9,oxymatrine phospholipid complex-stearic acid-soybean phospholipid-Kolliphor HS 15-ethanol(30:100:180:360:360);taking 50 mL of 4%mannitol solution as the external aqueous phase,ice bath stirring at 1 000 r·min^-1 and solidifying for 1 h,precooled at -20℃ for 24 h,took out and dried for 24 h.OMT-PC-SLN lyophilized powder was spherical in appearance with encapsulation efficiency of (38.09±1.24)%,average particle size of 785.5 nm,polydispersity coefficient(PDI) of 0.456 and the Zeta potential of -24.82 mV.The cumulative release rates of OMT-PC-SLN lyophilized powder were 72.63%at 2 h and 98.42%at 12 h;the cumulative release rate of oxymatrine(crude drug) was 98.60%at 2 h. Conclusion: This optimized formulation process of OMT-PC-SLN lyophilized powder is stable with good repeatability;compared with oxymatrine,OMT-PC-SLN lyophilized powder has a certain sustained-release effect.