Objective:To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma.Methods:Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed.Results:There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level.Conclusions:CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

OBJECTIVE: Hypertrophic scars (HS) are a variety of skin tissue fibrosis disease that occurs in human skin, the effective therapeutic method of which is still inaccessible up to now. As a bioactive constituent of a well-known medical plant, Salvia miltiorrhiza (Danshen in Chinese), tanshinone II_A (TSA) is reported to inhibit cell proliferation in HS. Therefore, the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site. The possible mechanism of action in suppressing HS was studied using human skin fibroblasts (HSF). METHODS: Tanshinone II_A self-dissolving microneedles (TSA-MN) was prepared using a negative mold casting method. The prescription process of microneedle was optimized by Box-Behnken effect surface method. Different media were selected to investigate the ability of transdermal absorption and in vitro release. Furthermore, according to Cell Counting Kit-8 (CCK8) method as well as the Western blot method, the effect of TSA-MN on the biological characteristics of HSF was investigated. RESULTS: With remarkable slow release effect and dermal retention, the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms. Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro, which plays a significant role in down-regulating the secretion of transforming growth factor-β₁ (TGF-β₁) in HSF and increasing the expression level of Smad7. CONCLUSION The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.

Deconvolution of potential drug targets of the central nervous system (CNS) is particularly challenging because of the complicated structure and function of the brain. Here, a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging. This strategy can map various substances including exogenous drugs, isotopically labeled metabolites, and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways. The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts, and can increase glutamate decarboxylase activity to elevate γ-aminobutyric acid (GABA) levels in the hypothalamus, agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation. These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.

Objective:To explore the application value of intraoperative awake combined with neuronavigation in surgery for eloquent area gliomas.Methods:Twenty patients with eloquent area gliomas, admitted to our hospital from October 2017 to June 2019, were chosen in our study. Preoperative blood oxygenation level dependent-functional MR imaging (BOLT-fMRI) was used to display the functional cortex in all patients, and diffusion tensor imaging (DTI) was used to reconstruct the peripheral fibrous tracts of the gliomas; after imaging fusion of above function structures, the data were imported into the neuronavigation system; intraoperative microscope was used to determine the functional areas in the cortex and the fiber bundle, and intraoperative awake combined with cortical stimulus was employed to determine the functional areas in the cortex again before removal of the tumors. Changes in patients' quality of life (Karnofsky performance scale, [KPS] scores) before surgery, 2 weeks after surgery, and 3 months after surgery were compared, and surgical-related complications or death were recorded.Results:Intraoperative awake combined with neuronavigation were successfully applied with the addition of cortical electrical stimulation in all 20 patients; 16 (80%) accepted total resection and 4 (20%) accepted subtotal resection. Follow-up for 2 weeks after surgery and 3 months after surgery showed that only one patient with high-grade glioma had decreased KPS scores than those before surgery, and there were no postoperative deaths or severe disabilities. As compared with KPS scores before surgery(83.02±4.76), those at 2 weeks after surgery (90.15±6.72) and 3 months after surgery (96.86±6.18) were significantly higher ( P<0.05). Conclusion:Intraoperative awake combined with neuronavigation can locate the eloquent area and fibers accurately, help neurosurgeons to resect gliomas totally in the surgery and protect patients' neuro-function.

Objective To explore the value of three antibodies in the differential diagnosis of papillary thyroid carcinoma ,by de‐tecting the expression of HBME‐1 ,CK19 and CD117 in papillary thyroid cacinoma ,thyroid follicular adenoma and Hashimoto′s thy‐roiditis tissues .Methods Totally 85 cases were collected from January 2013 to December 2015 ,including papillary thyroid cacino‐ma ,thyroid follicular adenoma and Hashimoto′s thyroiditis .They were immunohistochemical stained by HBME‐1 ,CK19 and CD117 .SPSS16 .0 software was used to analyze the relationship between the staining results with different pathological changes . Results The positive rates of HBME‐1 ,CK19 and CD117 were 87 .3% ,98 .2% ,and 7 .3% ,respectively .The positive expression of them in benign and malignant groups had significant difference (P< 0 .05) and their consistency checking Kappa were 0 .582 , 0 .551 ,and 0 .874 ,respectively .Conclusion In the differential diagnosis of papillary thyroid carcinoma and benign lesions ,CD117 is better than HBM E‐1 and CK19 .It′s possible to use a combination of them in practice .

Objective To explore the influnce on the endothelin-1 (ET-1) and clinical application value of continuous blood purification (CBP) on the treatment of severe craniocerebral injury with the neurogenic pulmonary edema (NPE).Methods All data about sixty patients with NPE were prospectively studied.These 60 patients were randomly (random number) divided into control group (n =30) and treatment group (n =30).In control group,patients were rapidly given with lowering intracranial pressure,mechanical ventilation,calming,antibiotic therapy and so on.In the treatment group,patients received CBP integrated with routine treatment.On admission and 72 h posttreatment,ET-1,static lung compliance and oxygenation index were observed.Time of mechanical ventilation support,incidence rates of multipal organ dysfunction syndrome (MODS) were compared between two groups.The paired t-test was used for the amount data within the group.Chi-square was used for the constitute ratio and incidence ratio of the each relevant information.P ＜ 0.05 was considered statistically significant.Results Compared to the control group,the level of ET-1 was decreased significantly in the treatment group [(48 ± 10) ng/L vs.(85 ± 14) ng/L] after 72 h post-treatment,while static lung compliance [(60.9 ± 2.3) mL/cmH2O vs.(31.4 ±4.8) mL/cmH2O] and oxygenation index [(317 ± 11) mmHg vs.(192 ± 14) mmHg] increased significantly (P ＜ 0.05).In treatment group and control group,the time of respirator intervention were [(6.0 ± 2.1) d vs.(11 ± 3.2) d],and the statistical significance was shown (P ＜ 0.05).Compared to the control group [56.7％ (17/30)],incidence rate of MODS [20.0％ (6/30)] was lower in treatment group (P ＜ 0.05).Conclusions CBP combined with routine treatment,which can remove ET-1 effectively,improve oxygenation,reduce the time of mechanical ventilation support and incidence rate of MODS.

To explore the relationship between maternal insulin levels and fetal insulin resistance.Maternal blood and venous cord blood samples were collected in gestational diabetes mellitus (GDM) mothers and control subjects.The glucose and insulin levels were measured and insulin resistance levels estimated.Maternal levels of insulin and homeostasis model of assessment for insulin resistance index (HOMAIR) were significantly higher in the GDM group than those in the control group (P ＜ 0.05) ; fetal levels of insulin and HOMA-IR were significantly higher in the GDM group than in the control group (P ＜ 0.05).Maternal insulin level positively correlated with fetal insulin (r =0.326,P ＜ 0.05) and HOMA-IR levels (r =0.378,P ＜0.05).In this study,a higher level of fetal insulin resistance was reported in the GDM group.And maternal hyperinsulinemia might affect fetal insulin resistance in pregnant women with GDM.

Objective To assess lipid status of pregnant women with GDM based on the lipid reference intervals for pregnant women .Methods Maternal blood and venous cord blood samples were collected in 81 well-controlled GDM mothers and 86 control subjects .The total cholesterol (CHOL) ,trigalloyl glycerol (TRIG) ,high-density lipoprotein cholesterol (HDL) ,low-density lipo-protein cholesterol (LDL) ,apolipoprotein A1 (ApoA) ,apolipoprotein B (ApoB) and lipoprotein (a) levels were measured by auto-matic biochemical analyzer .We used a normal pregnancy specific lipid reference interval (PSR) and normal non-pregnant reference intervals (NPR) respectively to assess the lipid status of pregnant women with GDM .Results Compared with normal control group ,the Apo A ,HDL and LDL levels in GDM group were significantly lower (P<0 .05) .The HDL ,LDL and Lp(a) levels of GDM cord blood were significantly lower (P<0 .05) .The weight of offspring birth of GDM pregnant women with low level HDL was significantly higher (P<0 .05) ,and that of GDM pregnant women with high level LDL offspring birth weight was significantly lower (P<0 .05) .Maternal HDL was not correlated with birth weight (r= -0 .190 ,P=0 .103) .Parent LDH and birth weight was negatively correlated (r= -0 .252 ,P=0 .029) .Conclusion The reference range of normal pregnancy-specific lipid we had estab-lished is more scientific for assessment of blood lipids .

ObjectiveTo investigate the relationship between ceruloplasmin expression and Down syndrome (DS). MethodsDifferential protein expression in serum of six mothers with DS fetuses and six mothers with healthy fetuses was detected by two-dimensional electrophoresis and matrix assisted laser desorption ionization-mass spectrum,the results were confirmed by Western blot.The levels of serum ceruloplasmin in 11 mothers with DS fetuses,10 mothers with healthy fetuses,11 DS newborns and 10 healthy babies were detected by enzyme-linked immunosorbent assay.The difference between the two groups was compared by two-independent samples t test. ResultsTwenty-nine differential proteins were found in the serum of the mothers with DS fetuses; among which ceruloplasmin increased significantly compared with that in mothers with healthy fetuese with density ratio of 5.43 (t=2.7102,P＜0.05).Western blot results showed that the expression of ceruloplasmin in maternal serum with DS fetuses (0.95 ± 0.24) was higher than that of normal mothers (0.37±0.14) (t=2.9521,P＜0.05) ; while the expression of ceruloplasmin in DS babies' serum (0.74±0.03) was lower than that of normal newborns (0.89±0.06)(t=-2.9515,P＜0.05).The expression of ceruloplasmin in serum of mothers with DS fetuses [(346.5± 111.8) ng/ml] was higher than that of normal mothers [(248.6478.3) ng/ml] (t=2.301,P＜0.05) ; while the expression of ceruloplasmin in DS babies' serum [(166.1 ±55.0) ng/ml] was lower than that of normal newborns [(244.0±36.0) ng/ml] (t=-3.873,P＜0.01). ConclusionsAbnormal maternal and neonatal serum ceruloplasmin level might relate to DS.