Objective Galactosialidosis(GS) is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal ?-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A(PPCA).Mouse model of GS has been generated by targeted deletion of PPCA gene and closely resembled the phenotypes in human conditions.However,it remains to be determined whether hearing loss observed in human also occurs in the mouse model.In this study,we observed their alterations of the auditory function and morphology of the ear,and explored pathophysiological mechanisms of hearing impairment.Methods PPCA homozygous(PPCA-/-) mice at 1 and 2 months of age,and their wildtype littermates(PPCA+/+) were examined for auditory thresholds through auditory brainstem responses(ABR) to click,tone pips 8,16,and 32 kHz stimuli.Morphological analyses in ears were performed by series temporal bone section and light microscopy.Results PPCA-/-mice at 1 month of age showed a normal threshold and the morphology of ears.Up to 2months of age,their thresholds were elevated 40～45 dB SPL above those of PPCA+/+ mice.There were distinct pathological changes of middle and inner ear in PPCA-/-mice of 2 months old.The severe otitis media and the vacuolation associated with lysosomal storage were observed within ossicles and cochlear bone cells,stria vascularis cells,spiral ganglion neurons,spiral limbus,Reissner's membrane cells,and the mesothelial cells of the perilymphatic scala and basilar membrane,but not within the organ of Corti.Vestibular organ did not show vacuolation.Conclusion The deficiency of lysosomal protective protein/cathepsin A may result in hearing loss and morphological alterations of ear.The otitis media and ossicle changes,and the defects in lysosomal storage of neurons,stria vascularis,spiral limbus,Reissner's membrane and basilar membrane cells may contribute to the conductive and sensorineural hearing loss respectively.

Objective: To study the expression of Survivin protein and its relationship with apoptosis in oromaxillofacial sarcoma(OMFS). Methods:The expression of Survivin protein and apoptosis were assessed by immunohistochemical staining and TUNEL method in 37 OMFS samples and 14 oral benign mesenchymal tumor(BMT) samples.Results:The Survivin positive rate in oromaxillofacial sarcomas was 81.08% and none in benign tumors(P

Objective To evaluate the efficacy and safety of sublingual immunotherapy (SLIT) in patients with allergic asthma in order to provide reliable evidence for clinical application of SLIT.Methods To search published articles of randomized controlled trials (RCTs) in allergic asthma from CNKI,WANFANG,Pubmed and Medline databases.The methodological quality of trials was assessed by Jadadscale.The heterogeneity was examined by using Stata 11.0 software.Fixed effect model or random effect model was used to pool the data.The articles which could not be pooled were carried out by descriptive analysis.The Egger's and Begg's test were used to evaluate the publication bias.Results There were total 6 RCTs included in this text.Compared with control group,SLIT could significantly reduce asthma symptom scores (SMD =-0.89,95％ CI-1.36--0.43,P =0.000) and asthma medication scores (SMD =-4.53,95％CI-6.97--2.08,P =0.000),but not forced expiratory volume (FEV1) of lung function (SMD =0.19,95％ CI-0.02-0.41,P =0.078),neither serum sIgE levels (SMD =0.05,95％ CI -0.58-0.69,P =0.870).There were no obvious adverse events reported after treatment of SLIT.No publication bias were indicated by Egger's and Begg's tests.Conclusion SLIT significantly reduces asthma symptom scores and medication scores,suggesting that SLIT is a safe and effective approach of immunotherapy.However,it still needs more highly qualified studies of RCTs to prove.

OBJECTIVE: To explore the clinical characteristics and therapies for esophageal perforation complicated with lethal massive hemorrhage caused by esophageal foreign body. METHOD: To retrospective analysis the treatment of massive hemorrhage at the carotid artery or aorta caused by esophageal foreign body in forty seven patients, Foreign body characters, surgical approaches, and postsurgical management were summarized. RESULT: Among 24 patients with cervical esophageal foreign body, the object was removed either by esophagoscopy or through lateral cervical incision. After controlling carotid artery hemorrhage and repairing Fistula of artery from cervical incision, 19 patients survived. For the 23 patients with thoracic esophageal foreign body accompanied with aorta hemorrhea, thoracotomy was performed to remove the foreign body and repair the aortic fistula. Only 3 of these 23 patients recovered from the emergent surgery, other 20 patients died. CONCLUSION For the patients with esophageal foreign body inducing large vessel impingement, the most reliable therapeutic method is surgical repairing of arterial perforation and extraction of the foreign body via cervical or thoracic incision. Carotid ligation should be considered in patients with recurrent carotid hemorrhage. For the patient with mediastinitis, esophageal exclusion is recommended to prevent infection and to promote healing of aortic perforation after aortic fistula repairing.
Adult ; Esophageal Perforation ; etiology ; surgery ; Esophagus ; Female ; Follow-Up Studies ; Foreign Bodies ; complications ; Hemorrhage ; etiology ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo examine whether calcineurin/NFAT signaling pathway mediates endothelin-1 (ET-1)-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) by regulating phosphodiesterase-5 (PDE5) and the effect of the selective calcineurin inhibitor cyclosporine A and PDE5 inhibitor sildenafil on ET-1-induced PASMC proliferation.

METHODSPASMCs were treated with ET-1 to stimulate their proliferation with or without prior treatment of the cells with CsA or sildenafil. Calcineurin activity in the cells was measured using a calcineurin activity assay kit, PDE5 expression examined using immunoblotting, and cGMP level detected using a cGMP direct immunoassay kit. PASMC proliferation following the treatments was determined using [(3)H]thymidine incorporation assay.

RESULTSET-1 caused a 2.05-fold increase in the cellular calcineurin activity, a 1.80-fold increase in PDE5 expression, and a 3.20-fold increase in the DNA synthesis rate, and reduced the cGMP level by 67%. Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Both Cyclosporine and sildenafil suppressed ET-1-stimulated PASMC proliferation.

CONCLUSIONActivation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Both Cyclosporine and sildenafil can suppress ET-1-stimulated PASMC proliferation in vitro.

Animals ; Calcineurin ; metabolism ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; metabolism ; Cyclosporine ; DNA ; biosynthesis ; Endothelin-1 ; pharmacology ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; enzymology ; NFATC Transcription Factors ; metabolism ; Piperazines ; Pulmonary Artery ; cytology ; Purines ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Sildenafil Citrate ; Sulfones

A mixed drug self-delivery system(DSDS)with high drug content(＞50％)was developed to regulate pH-triggered drug release,based on two doxorubicin(DOX)-DOX dimmers:D-DOXADH and D-DOXcar con-jugated with acid-labile dynamic covalent bonds(hydrazone and carbamate,respectively)and stabilized with PEGylated D-DOXADH(D-DOXADH-PEG).Owing to the different stability of the dynamic covalent bonds in the two dimers and the noncovalent interaction between them,pH-triggered drug release could be easily regulated by adjusting the feeding ratios of the two DOX-DOX dimers in the mixed DSDS.Similar in vitro cellular toxicity was achieved with the mixed DSDS nanoparticles prepared with different feeding ratios.The mixed DSDS nanoparticles had a similar DOX content and diameter but different drug releasing rates.The MTT assays revealed that a high anti-tumor efficacy could be achieved with the slow-release mixed DSDS nanoparticles.

Objective: The etiology of schizophrenia is unknown and is associated with abnormal spontaneous brain activity. There are no consistent results regarding the change in spontaneous brain activity of people with schizophrenia. In this study, we determined the specific changes in the amplitude of low-frequency fluctuation/fractional amplitude of low-frequency fluctuation (ALFF/fALFF) and regional homogeneity (ReHo) in patients with drug-naïve first-episode schizophrenia (Dn-FES). Methods: A comprehensive search of databases such as PubMed, Web of Science, and Embase was conducted to find articles on resting-state functional magnetic resonance imaging using ALFF/fALFF and ReHo in schizophrenia patients compared to healthy controls (HCs) and then, anatomical/activation likelihood estimation was performed. Results: Eighteen eligible studies were included in this meta-analysis. Compared to the spontaneous brain activity of HCs, we found changes in spontaneous brain activity in Dn-FES based on these two methods, mainly including the frontal lobe, putamen, lateral globus pallidus, insula, cerebellum, and posterior cingulate cortex. Conclusion We found that widespread abnormalities of spontaneous brain activity occur in the early stages of the onset of schizophrenia and may provide a reference for the early intervention of schizophrenia.

OBJECTIVE: To enhance the safety of nasal endoscopic surgery and decrease its complications of eyes. METHOD: Three patients of chronic rhinosinusitis and nasal polyposis with lipogranulomas of the eyelids after nasal endoscopic surgery and nasal packing of petrolatum gauze were reported and analyzed, and their treatment results were presented during the last 2 years. RESULT: The medial orbital wall injury occurred in all three patients during endoscopic sinus surgery. The patients developed an ipsilateral periocular swelling, eyelid hematoma and palpebral conjunctival edema during 2 to 3 hours after surgery. Nasal packs petrolatum gauze were removed 10-24 hours after surgery. The patients were discharged from hospital when periorbital swelling and eyelid ecchymoma disappeared, and nasal cavity obstruction was improved 6 to 8 days after surgery. The swelling and nodular mass of ipsilateral eyelids (one in left upper eyelid and two in right lower eyelid) were found 12-15 days after surgery, and their eye movement and eyesight were normal. Antibiotic and corticosteroid were administered for 3 4 weeks with only improvement in eyelid swelling. These masses of eyelids were completely excised through palpebral margin 1-6 months after surgery. The histopathological examination of the surgical specimens showed lipogranuloma. No recurrence and symptom of the eyes had been observed during 4-18 months follow up. CONCLUSION The lipogranuloma of the eyelid is a rare and late complication after nasal endoscopic surgery and nasal packing with vaspetrolatum gauze. The medial orbital wall injury and bleeding during surgery, and vaseline of nasal packing permeated into the eyelid are the direct causes of this complication. The application of petrolatum gauze should be avoided when the medial orbital wall trauma is identified. The complete excision of granulomas is a best effective therapy.
Adult ; Endoscopy ; adverse effects ; Eyelid Diseases ; diagnosis ; etiology ; therapy ; Female ; Granuloma ; diagnosis ; etiology ; therapy ; Humans ; Male ; Middle Aged ; Postoperative Complications ; diagnosis ; therapy

Objective lo investigate the predictive value of serum growth differentiation factor 11(GDF-11)and calprotectin A4(S100A4)for contrast-induced nephropathy(CIN)after coronary angiography(CAG).Methods A total of 528 patients who underwent CAG in the First Affiliated Hospital of Xi'an Jiao-tong University from December 2020 to November 2023 were selected as the research objects.According to whether the patients had CIN,they were divided into non-nephropathy group(472 cases)and nephropathy group(56 cases).Enzyme-linked immunosorbent assay was used to detect serum levels of GDF-11 and S100A4.Multivariate Logistic regression analysis was used to explore the influencing factors of CIN after CAG.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum GDF-11 and S100A4 for CIN after CAG.Results The serum levels of GDF-11 and S100A4 in nephropathy group were higher than those in non-nephropathy group(P＜0.05).The contrast agent dose and postoperative ser-um creatinine level in the nephropathy group were higher than those in the non-nephropathy group(P＜0.05).Multivariate Logistic regression analysis showed that contrast agent dose ≥131.84 mL(OR=2.158,95％CI 1.284-3.627),postoperative serum creatinine ≥ 87.57 μmol/L(OR=2.445,95％CI 1.533-3.898),GDF-1 1 ≥4 50.84 ng/mL(OR=2.445,95％CI 1.533-3.898)were the influencing factors of CIN af-ter CAG(P＜0.05).The area under the curve(95％CI)of serum GDF-11 and S100A4 for predicting CIN af-ter CAG was 0.861(95％CI 0.810-0.912)and 0.798(95％CI 0.747-0.849),respectively.The optimal cut-off values were 450.84 ng/mL and 86.98 μg/mL,the specificity were 65.89％and 57.62％,and the sensi-tivity were 94.74％and 94.74％,respectively.The area under the curve of the combination of the two was 0.906(95％CI 0.856-0.957),the specificity was 87.09％,and the sensitivity was 84.26％.Conclusion The elevated levels of serum GDF-11 and S100A4 are closely related to the occurrence of CIN in patients after CAG surgery,which can be used as biological indicators to evaluate the occurrence of CIN in patients after CAG surgery,and the combined prediction efficiency of GDF-11 and S100A4 is higher.

OBJECTIVETo examine the correlation of the changes in the serum markers (C-reactive protein, endothelin-1, interleukin-6, and brain natriuretic peptide) with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension secondary to COPD.

METHODSA total of 174 COPD patients with acute exacerbation, admitted between February 2011 and February, 2013, were enrolled in this study, with 43 volunteers with normal pulmonary functions as controls. Pulmonary arterial pressure was determined by Doppler echocardiograph, and the severities (mild, moderate and severe) of PH secondary to COPD was evaluated. The levels of serum markers were determined using ELISA kits.

RESULTSThe levels of serum markers in patients with COPD was significantly elevated compared with those of the control subjects (P<0.05), and further increased in patients with pulmonary hypertension secondary to COPD (P<0.05). A positive correlation was found between these serum markers and pulmonary artery pressure in COPD patients with mild and moderate pulmonary hypertension. In patients with severe pulmonary hypertension, only the serum level of brain natriuretic peptide continued to increase with pulmonary artery pressure (P<0.05), and the other markers did not further increase.

CONCLUSIONSEarly and combined examination of these serum markers in patients with COPD can help to identify pulmonary hypertension in early stage and estimate the severity of pulmonary hypertension. Hemodynamic monitoring of the changes of these serum markers can be of important clinical value in the treatment of pulmonary hypertension secondary to COPD and in evaluation of the prognosis of COPD.

Aged ; Biomarkers ; blood ; Blood Pressure ; C-Reactive Protein ; metabolism ; Endothelin-1 ; blood ; Female ; Humans ; Hypertension, Pulmonary ; blood ; complications ; physiopathology ; Interleukin-6 ; blood ; Male ; Natriuretic Peptide, Brain ; blood ; Pulmonary Disease, Chronic Obstructive ; blood ; complications ; physiopathology