Adenofibroma ; metabolism ; pathology ; Antigens, CD34 ; metabolism ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Neoplasms, Germ Cell and Embryonal ; metabolism ; pathology ; surgery ; Nephroma, Mesoblastic ; metabolism ; pathology ; Sarcoma, Clear Cell ; metabolism ; pathology ; Stromal Cells ; metabolism ; pathology ; Vimentin ; metabolism

Objective To evaluate the effect of intravenous thrombolysis with urokinasc for treatment of acute cerebral infarction due to vertebrobasilar artery ischemia.Methods Thirteen pafients with a clinical diagnosis of acute cerebral infarction arising from vertebrobasilar artery ischemia received thmmbolytic therapy with urokinase(5×105-1.5×106U) infused intravenously within 1 h.The NIH Stroke Scale(NIHSS)was used to evaluate the patients'neurological function before and at 0,6,24 hand at 7 and 14 days after the treatment.Modified Rankin Scale(MRS)was used for neurologiical assessment 3 months after the treatments. Results The mean NIHSS score of the patients was 17.46±6.19 before treatment and rapidly decreased to 7.92±6.43 24 h after the thrombolytic therapy.Three months after the therapy,8 patients had favorable clinical outcomes defined as capability of independent living(MRS score of 0-2);2 patients had a poor outcomes with assisted living,and 3 patients died.Bleeding occurred in 4 cases including 2 cerebral hemorrhage cases. Conclusion Favorable clinical outcome can be achieved with intravenous urokinase therapy in the majority of patients with acute cerebral infarction due to vertebrobasilar ischcrnia.

Animals ; Gonadal Hormones ; therapeutic use ; Growth Hormone ; therapeutic use ; Hormones ; therapeutic use ; Humans ; Insulin ; therapeutic use ; Neoplasms ; drug therapy ; Thyroid Hormones ; therapeutic use

AIMTo determine the effects of the functional domain of saposin C (neurotrophic peptide [NP]) on androgen receptor (AR) expression and transcriptional activity.

METHODSWe constructed DNA vectors expressing NP or a chimeric peptide of the viral TAT transduction domain and NP (TAT-NP) using gene cloning technology. The effects of ectopic expression of NP or TAT-NP on cell growth were examined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, transient transfection and reporter gene assays were used to determine the effects of NP on AR expression and activation.

RESULTSNP stimulated proliferation of androgen responsive LNCaP cells in the absence of androgens. RT-PCR and Western blot analyses showed that ectopic expression of NP resulted in induction of AR gene expression, and that the NP-stimulated expression of AR could be synergistically enhanced in the presence of androgens. Furthermore, reporter gene assay results showed that NP could enhance AR transactivation by increasing androgen-inducible gene reporter activity.

CONCLUSIONWe provided evidence that ectopic expression of saposin C-originated NP could upregulate AR gene expression and activate the AR transcriptional function in an androgen-independent manner in prostate cancer cells.

Cell Division ; Cell Line, Tumor ; DNA, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Humans ; Kinetics ; Male ; Nerve Growth Factors ; genetics ; Pancreatic Neoplasms ; genetics ; pathology ; RNA, Messenger ; genetics ; Receptors, Androgen ; genetics ; Restriction Mapping ; Reverse Transcriptase Polymerase Chain Reaction ; Saposins ; metabolism ; Transcription, Genetic ; Up-Regulation

Aim To investigate the molecular mecha-nisms of the Wenyang Huazhuo Tongluo formula in in-hibiting endothelial-to-mesenchymal transition(En-doMT)of pulmonary microvascular endothelial cells and improving pulmonary microvascular injury in sys-temic sclerosis(SSc).Methods Pulmonary micro-vascular endothelial cells were cultured with serum from SSc patients to establish SSc pulmonary microvas-cular endothelial cells.A hypoxia model was estab-lished in SSc pulmonary microvascular endothelial cells using liquid paraffin sealing,and the cells were treated with the Wenyang Huazhuo Tongluo formula or HIF-1a inhibitor KC7F2.Western blot was used to detect the protein expression levels of VE-cadherin,CD31,vimen-tin,HIF-1α,Foxm1,smad3,Tie-1,and vWF.ELISA was used to measure the concentrations of E-selectin and ICAM-1 in cell culture medium.The luciferase re-porter gene system was used to detect the promoter ac-tivity of the Foxm1 gene.Results Compared to the control group,the levels of VE-cadherin,CD31,HIF-1α,Foxm1,smad3,Tie-1,and vWF significantly de-creased under hypoxic condition,while the levels of vi-mentin,E-selectin,and ICAM-1 significantly in-creased.In addition,the cell morphology exhibited a distinct"spindle-like"myoblast morphology.Treat-ment with the Wenyang Huazhuo Tongluo formula or KC7F2 reversed these changes in protein expression levels and cell morphology induced by hypoxia.Con-clusion The Wenyang Huazhuo Tongluo formula im-proves pulmonary microvascular injury in SSc by inhib-iting the HIF-1a/Foxm1/smad3 pathway-mediated En-doMT of pulmonary microvascular endothelial cells.

OBJECTIVETo determine whether early application of Duo positive airway pressure (DuoPAP), in comparison with nasal continuous positive airway pressure (NCPAP), can reduce the need for endotracheal intubation and mechanical ventilation and decrease the incidence of bronchopulmonary dysplasia (BPD) in preterm neonates with respiratory distress syndrome (RDS).

METHODSIn a single-center, randomized controlled trial, preterm neonates (gestational ages 30-35 weeks) with RDS were randomly assigned to receive DuoPAP (n=34) or NCPAP (n=33) within 6 hours of birth. If the two noninvasive ventilations were not effective, endotracheal intubation and mechanical ventilation were used, and pulmonary surfactant was administered as rescue therapy. The total invasive respiratory support rate and incidence of BPD within 24, 48 and 72 hours of birth were observed. The two groups were compared in terms of PaCO2, PaO2 and oxygenation index (OI) at 1, 12, 24, 48 and 72 hours after using the noninvasive respiratory support.

RESULTSThe total invasive respiratory support rates within 48 and 72 hours after birth were significantly lower in the DuoPAP group than in the NCPAP group (P<0.05). There was no difference in the incidence of BPD between the two groups (P>0.05). The OI in the DuoPAP group was significantly higher than in the NCPAP group at 1, 12, 24, 48 and 72 hours after noninlasive respiratory support (P<0.05). The DuoPAP group showed significantly lower PaCO2 than the NCPAP group at 1, 12, and 24 hours after noninvasive respiratory support (P<0.05). PaO2 was significantly higher in the DuoPAP group than in the NCPAP group at 1 and 12 hours after noninvasive respiratory support (P<0.05).

CONCLUSIONSCompared with NCPAP, early application of DuoPAP can decrease the need for endotracheal intubation and mechanical ventilation in preterm neonates with RDS, showing promise for broad use.

Bronchopulmonary Dysplasia ; epidemiology ; Continuous Positive Airway Pressure ; methods ; Female ; Humans ; Infant, Newborn ; Intermittent Positive-Pressure Ventilation ; methods ; Male ; Noninvasive Ventilation ; methods ; Respiratory Distress Syndrome, Newborn ; therapy

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Background: Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients. Methods: This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography. Results: Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037). Conclusion Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Abstract：Objective To predict the structure and function of sterol O⁃acyltransferase 1（SOAT1）related to hepatocellular carcinoma（HCC）by using bioinformatics tools，in order to understand its mechanism as the marker and therapeutic target of S⁃Ⅲ subtype. Methods The structure，function and protein interaction of SOAT1 were predicted and analyzed by using databases or softwares such as NCBI，STRING，Protscale，SignalP，TMHMM，PSORT，SOPMA，SWISS ⁃ MODEL， NetNGlyc，NetOGlyc，Netphos and ProtParam. Results The protein encoded by SOAT1 was a hydrophobic protein with good stability，which was a nonclassical pathway protein with 8 transmembrane regions，mainly distributed among the cell membrane. SOAT1 was expressed in many tissues，while most of them in the adrenal gland，which showed multiple phosphorylation sites and was mainly involved in the synthesis and catabolism of cholesterol. Conclusion Bioinformatics analysis of structure and function of SOAT1 showed that SOAT1 lipid synthesis and catabolism pathways played an important role，and lipid expression was closely related to the development of cancer，indicating that the treatment of HCC may be achieved by regulating the expression of SOAT1 gene.