ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(△SIi),while the percentage of relative changes of year j(ranging from 2 to 51 was calculated with △SIj compared to △SIi(Rchangej).The values of these two parameters were compared,and the correlation of △SI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age nor △SI1 was found between groups(all P＞0.05).The second to the fifth year △SI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P＜0.05).Within both groups,△SI was positively correlated with GBCA injection year-time(both P＜0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

A 6-year-old girl presented with recurrent skin rash at the initial stage, recent joint pain, and neutrophilia was found during a routine blood test. After a multidisciplinary case discussion, she was diagnosed with chronic neutrophil leukemia, and the symptoms were relieved after hydroxyurea and luxolitinib treatment. She received the allogeneic hematopoietic stem cell transplantation subsequently. At present, she is in stable condition and under follow-up. Chronic neutrophil leukemia is a rare disease, which rarely occurs in children. It is more difficult to diagnose in patients with skin rash as the first manifestation. The diagnosis and treatment of this case reflects the important role of multidisciplinary cooperation in the diagnosis and treatment of difficult and rare diseases.

Objective:To observe the expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) in the inner limiting membrane (ILM) of diabetic retinopathy (DR) with macular edema, and analyze the correlation between VEGF and AQP4 expression.Methods:A cross-sectional study. From September 2019 to September 2020, 38 eyes of 38 patients with DR and idiopathic macular hole (iMH) who underwent vitrectomy (PPV) combined with ILM stripping at the Hangzhou campus of The Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. Among them, there were 25 males and 13 females who aged 37-76 years old, average age was 59±10 years old; All eye included 15 right eyes and 23 left eyes. iMH and DR included 9 eyes in 9 cases and 29 eyes in 29 cases, respectively, and they were divided into iMH group and DR group. The DR group was divided into DME group and no DME group according to whether it was accompanied by diabetic macular edema (DME), with 14 eyes and 15 eyes respectively. After the stripped ILM tissue was fixed, immunofluorescence analysis was performed to obtain a picture of the fluorescence mode of AQP4 and VEGF, and the fluorescence intensity value of VEGF and AQP4 was measured by Image J software. The differences of VEGF and AQP4 immunofluorescence values in the specimens between groups were compared by one-way analysis of variance. The correlation between the fluorescence intensity of AQP4 and the fluorescence intensity of VEGF was analyzed by Pearson correlation analysis.Results:The average fluorescence intensity valuesof VEGF and AQP4 in ILM specimens of DME group, no DME group and iMH group were 38.96±7.53, 28.25±3.12, 30.07±4.84 and 49.07±8.73, 37.96±6.45, 38.08±5.04, respectively. The average fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DME group was significantly higher than that of the no DME group and iMH group, and the difference was statistically significant ( F=13.977, 9.454; P<0.05). The average fluorescence intensity values of VEGF and AQP4 on IML specimens in the DR group were 33.80±7.91, 43.76±9.44, respectively. The results of Pearson correlation analysis showed that the fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DR group was significantly positively correlated ( r=0.597, P=0.003). Conclusions:The expressions of VEGF and AQP4 in ILM of eyes with DR and DME are significantly increased compared with those without DME. The expression of VEGF and AQP4 in ILM of eyes with DR is positively correlated.

OBJECTIVE: To investigate the prognostic value of preoperative serum tumor markers combined with peripheral blood routine indexes in colorectal cancer patients. METHODS: From January 2010 to March 2013, clinicopathological data of colorectal cancer patients receiving surgery treatment at the Third Affiliated Hospital of Sun Yat-sen University were collected. INCLUSION CRITERIA: (1) histologically confirmed adenocarcinoma; (2) primary cancer resected; (3) intact clinical data; (4) no signs of clinical infection. Patients with intestinal perforation or obstruction, hematological diseases or other malignant tumors were excluded. Informations were recorded containing sex, age, tumor location, degree of differentiation, tumor size, vascular tumor thrombus, nerve invasion, depth of infiltration, lymph node metastasis, distant metastasis, TNM stage, peripheral serum CEA, CA199, number of neutrophil, monocyte, platelet and lymphocyte. Positive CEA was defined as ≥5 μg/L, CA199 as ≥35 U/L; while NLR (neutrophil-to-lymphocyte ratio), MLR (monocyte-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) greater than their cut-off values were defined as positive. ROC curve was used to determine the cut-off values (with greatest area under curve) of NLR, MLR and PLR. The prognostic values of these indexes were analyzed using Kaplan-Meier regression and log-rank test. COX regression was used to perform risk factor analysis. RESULTS: A total of 312 colorectal cancer patients were enrolled, including 192 males and 120 females with median age of 61 (15-85) years. Till March 11, 2018, during median follow-up period of 65 months(2-96), the follow-up rate was 90.4% with loss of 30 cases and the mortality was 37.2% with 116 death. Univariate analysis found that colorectal cancer patients with positive CEA, CA199, NLR (>2.32), MLR (>0.24) and PLR (>164.1) had poor prognosis (all P<0.01). When combining CEA, CA199 with NLR, MLR, PLR, the survival analysis showed that patients with both negative indexes had the best prognosis, one positive the worse and both positive were the worst (all P<0.01). COX regression revealed that CEA(HR= 1.702,95%CI:1.148-2.522, P<0.01), combination of CA199 and MLR (HR=2.292, 95%CI:1.426-3.683, P<0.01) were independent risk factors for colorectal cancer. CONCLUSION Combination of preoperative serum tumor markers and peripheral blood routine indexes can provide prognostic information for the patients with colorectal cancer.
Aged ; Aged, 80 and over ; Biomarkers, Tumor ; blood ; Blood Platelets ; Colorectal Neoplasms ; blood ; diagnosis ; Female ; Humans ; Lymphocytes ; Male ; Middle Aged ; Neoplasm Staging ; Neutrophils ; Prognosis ; Retrospective Studies

Objective To investigate the morphological factors related to the rupture of very small (≤3mm) anterior communicating artery (AComA) aneurysms, which provides basis for decision-making of whether or not taking intervention in very small un-ruptured AComA aneurysms. Methods (1) One hundred patients with primary AComA aneurysms, admitted to our hospital from January 2008 to June 2013, were enrolled; 84 AComA aneurysms were ruptured while 16 were un-ruptured; the morphological parameters of aneurysms were obtained by three-dimensional reconstruction with CT angiography (CTA) of the patients, and the clinical data and aneurysm morphological parameters were compared between the ruptured aneurysm group and the un-ruptured aneurysm group; multivariate Logistic regression was used to analyze the risk factors of small aneurysm rupture in the AComA, and receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of size ratio (SR) of maximum tumor depth to proximal carrier artery diameter in rupture of small aneurysms in the AComA. (2) Ninety-nine patients with primary AComA aneurysms, admitted to our hospital from June 2013 to January 2016, were enrolled; the parameters from the above analyses were applied to these patients to verify their predictive effectiveness. Results (1) Perpendicular height, AR value (Height/Neck), SR value and vessel angle were significantly different between ruptured aneurysm group and un-ruptured aneurysm group (P<0.05); multivariate Logistic analysis indicated that SR value was the independent risk factor of rupture of very small AComA aneurysms (OR=4.201, 95％CI: 1.175-15.019, P=0.012), and the lager the SR value, the higher the risk of rupture; ROC curve analysis revealed that the area under the curve was 0.699 with the optimal cut-off value being 0.9, and its diagnostic sensitivity, specificity and accuracy was 0.786, 0.625 and 0.760, respectively. (2) The SR value was then applied to the 99 patients, showing a stable predictive potential with sensitivity, specificity and accuracy of 0.676, 0.714 and 0.687, respectively. Conclusion SR value (≥0.9) is identified as independent morphological risk factor for rupture of very small AComA aneurysms; SR value is closely related to the state of aneurysms, which help make a better individualized and effective decision on the treatment of very small AComA aneurysms in clinic.

Objective: To explore the electrocardiographic characteristics of patients with idiopathic ventricular arrhythmias (VAs) originating from different portions of distal great cardiac veins (DGCV). Methods: The study included 49 patients underwent successful RFCA of premature ventricular complex(PVCs)/ventricular tachycardia(VT) from different portions of the DGCV in our department from July 2009 to March 2016. The surface 12-lead electrocardiogram (ECG) and intraventricular ablation mapping features were analyzed. Patients were divided into four groups according to the mapping and ablation results: DGCV1(10 patients), DGCV2 (13 patients), proximalanterior interventricular vein (PAIV, 17 patients)and extend distal great cardiac vein (EDGCV, 9 patients). We analyzed the similarities and differences between surface 12-lead ECG of patients with PVCs/VT from different portions of DGCV, and compared with random chosen 290 patients with PVCs/VT from ventricular outflow tract and adjacent structure. Results: A positive R wave in inferior leads, a negative QS morphology in lead aVL and aVR were found among all groups. The different characteristics of surface 12-lead ECG of VAs originating from DGCV were as follows: (1)EDGCV patients demonstrated a positive R or r wave on lead Ⅰ(6/9) while a negative rS or qr wave was evidenced in other three groups (39/40). (2)A positive R pattern on lead V₁, V₅-V₆ (11/13) was presented in patients of DGCV2 group; R (without S or s) wave on V₁ (9/10), RS or Rs wave on V₅-V₆ were found in DGCV1 group; RS or rS wave was seen on lead V₁, R(without S)wave in lead V₅-V₆ (25/26) were found in EDGCV and PAIV group and the amplification of R wave in EDGCV was higher than V₁ of PAIV group.(3)Precordial lead transition zone was in front of V₁ for DGCV1 and DGCV2 groups (23/23), within V₁-V₃ for EDGCV group, but on V₂ or within V₂-V₃ for PAIV group.(4)Patients of DGCV1 and DGCV2 demonstrated a longer Pseudo delta wave time(PdW), intrinsicoid deflection time (IDT), significantly larger maximum deflection index (MDI) than those in PAIV and EDGCV groups (P<0.001). (5)The different characteristics of surface 12-lead ECG between VAs originating from DGCV and those from ventricular outflow tract and adjacent structure were as follows: ① The ECG features were similar between PVIA and LCC group, both demonstrated a rs wave on the lead Ⅰ, rS wave on V₁-V₂ and R wave on V₅-V₆; ②The ECG features were similar betweenEDGCV and RCC group, both presented with R or r wave on the lead Ⅰ, the QRS wave of precordial leads was similar as PAIV and LCC groups; ③A R wave on the lead V₁, V₅-V₆ was found in group DGCV2, and ILCC; ④Similar to the group Endo-MAA, patients in DGCV1 group also demonstrated a R wave on the lead V₁ and a Rs wave on V₅-V₆. Conclusion A positive R wave in inferior leads, a negative QS morphology in lead aVL and aVR are seen in all patients, but different electrocardiographic characteristics of PVC/VT originating from the different portions of the DGCV are presented on lead Ⅰ and V₁-V₆.

Objective To study the curative effect and prognosis of malignant pleural effusion treated by staphylotoxoid injection and its effect on immune system.Methods A total of 65 patients with malignant pleural effusion from August 2012 to 2014 November in Lishui City Central Hospital were selected,and divided into observation group(n=33) and control group (n=32) in terms of different treating methods,two groups were implemented with thoracic closed drainage to drain pleural effusion up.The observation group was completely drained after 2 500 U intrapleural injection of staphylotoxoid injection,the control group to the traditonal method of bleomycin 1 mg/kg injection.The efficacy,prognosis and immune system were compared.Results The effective of rate of the observation group was significantly higher(72.7%) than the control group(43.8%);the adverse reaction rate of observation group was lower and its median survival time was longer;white blood cells counts of observation group was significantly more than control group ( P<0.05).Conclusion Compared with the traditional method of bleomycin intrapleural injection treatment of malignant pleural effusion, staphylotoxoid injection can be more effective control of the disease , reduce adverse reactions, and can improve their immunity and improve the body tolerance .

Background & Objectives: Multiple sclerosis (MS), neuromyelitis optica (NMO) and acute transverse myelitis (ATM) are common diseases in neurology; however their corresponding cervical spinal cord involvements are still ambiguous. The purpose of this study was to demonstrate the utility of diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in identifying the injury in cervical spinal cord. Methods: Nine patients and nine healthy volunteers were enrolled in this study. Conventional sequences and DTI scan were performed on each participant. Results: The average fractional anisotrophy (FA) values of the cervical cord in patients with acute cerebral type MS, acute or stationary cerebrospinal type MS, acute NMO, or acute ATM were all significantly decreased relative to the control group (p <0.05). As to the cerebrospinal type MS, the changes in acute-stage patients were more apparent (p <0.05). The average FA value of the cervical cord in acute NMO was decreased more extensively, involving the normal-appearing spinal cord (p <0.05). In patients with MS or NMO, The lesions showed significantly hypointense on FA images and directionally encoded color (DEC) images, nevertheless the pathological areas on DTI images were no significantly different from those on routine sequences. On DTT, the fiber tracts in the lesion-involved regions were all sparser than that in control regions, nevertheless interruption or impairment of fiber tracts could only be noted in NMO patients. Bilateral differences of average FA values in the cervical cord was noted in one case with ATM and another case with MS (p <0.05), and the decrease of FA values was significant in the main side of clinical presentations. Conclusion: DTI and DTT may be a sensitive measure for early cervical injury in MS, NMO and ATM
Spinal Cord Diseases

OBJECTIVETo investigate the application of intense pulsed light (IPL) depilation in the auricular reconstruction with totally expanded skin and its suitable parameter.

METHODSFrom February 2009 to September 2013, one tissue expander(100 or 150 milliliters) were implanted under the skin of mastoid in 126 patients who suffered from microtia. During the skin expanding, the hair on the expanded skin was depilated by JPL technique. The parameter, operation, interval, the depilation result and the complication were recorded. The autologous rib cartilage frameworks were implanted in the second phase of auricular reconstruction.

RESULTSThe energy of IPL was 20 - 35 J/cm2 (mean 25. 3 J/cm2), the width of pulse was 26 - 30 ms ( mean 27. 9 ms), the interval between two operations was 4 weeks. Ninety-six patients were cured(76. 2%, 96/126). The total depilation efficient is 96. 8% (122/126). A fine banding blisters was found in one patient whose depilation areas was marked by black pen. Skin erythema was found in five patients and skin pigmentation was found in 7 patients. There were no skin necrosis and expander exposure in all patients. During 6 - 12 months of follow-up period, ninety-two patients were cured (73.0%, 92/126) and the total depilation efficient is 92. 9% (117/126).

CONCLUSIONSIPL depilation during the skin expanding is feasible and safe with careful procedure. The hairless expanded skin is enough to cover the framework, as well as the post-auricular area. The appearance of reconstructed ear is better without hair.

Congenital Microtia ; surgery ; Costal Cartilage ; transplantation ; Ear, External ; Erythema ; etiology ; Hair Removal ; methods ; Humans ; Mastoid ; Phototherapy ; adverse effects ; methods ; Reconstructive Surgical Procedures ; Skin Pigmentation ; Surgical Flaps ; Tissue Expansion ; Tissue Expansion Devices