OBJECTIVE: To study the expression of DNA-dependent protein kinase (DNA-PK) in human laryngeal squamous cell carcinoma (LSCC) and normal laryngeal mucosa (NLM), and to analysize the relationship between the expression and the clinicopathologic parameters of LSCC. METHOD: Immunohistochemical technique (Envision) was used to detect the expression of DNA-PK in 64 cases of LSCC and 15 cases of NLM. To investigate an investigation was conducted on the relationship between the expression and clinico-pathological features of LSCC. RESULT: DNA-PK was lowly expressed in NLM and highly expressed in LSCC,the positive rate of DNA-PK expression was 26.67% (4/15), 78.13% (50/64), respectively, and there was significant different difference between the two groups (P < 0.05). Its expression was correlated with the level of histodifferentiation (P < 0.05), but not with TNM stages and neck lymph node metastasis (P > 0.05). CONCLUSION DNA-PK may be involved in disease development of LSCC.
Aged ; Carcinoma, Squamous Cell ; enzymology ; pathology ; DNA-Activated Protein Kinase ; metabolism ; Female ; Head and Neck Neoplasms ; enzymology ; pathology ; Humans ; Laryngeal Mucosa ; enzymology ; Laryngeal Neoplasms ; enzymology ; pathology ; Larynx ; enzymology ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Middle Aged ; Squamous Cell Carcinoma of Head and Neck

In recent years, laser microdissection followed by mass spectrometry (LMD/MS) has been successfully applied to the proteomic studies of formalin-fixed paraffin-embedded (FFPE) renal tissues. This new technique improves the diagnosis of kidney diseases and has a better potential for future clinical application. The review focuses on the use of this methodology for exploring the mechanisms, diagnosis and classification of kidney diseases including renal amyloidosis and membrane proliferative glomerulonephritis.
Formaldehyde ; Humans ; Kidney ; pathology ; Kidney Diseases ; diagnosis ; Laser Capture Microdissection ; Mass Spectrometry ; Proteomics ; Tissue Fixation

Objective To analyze serum amyloid protein A (SAA) subtype and amino acid mutation sequence of the renal biopsy specimens from patients with renal amyloidosis secondary to ankylosing spondylitis (AS) by laser microdissection combined with mass spectometry.Methods Kidney biopsy formalin-preserved paraffin-embedded (FFPE) specimen slices were stained by Congo red,the positive areas of Congo red staining were selected by microdissection,after trypsin hydrolysis and filtration,peptide samples were subjected to liquid chromatography tandem mass spectrometry.Analysis softwares were used to evaluate the results,and the patient's amino acid sequence of SAA protein was compared to mutant amino acid sequence reported by literature or deduced from mutant SAA gene to determine whether there was a variation.Results SAA1 and SAA2 proteins with high abundance were identified by mass spectrometry,serum amyloid P and apolipoprotein E were also detected.No variation of SAA1 and SAA2 protein was detected.Conclusions The SAA1 and SAA2 proteins in AA amyloidosis secondary to ASwere identified for the first time,which enriched the pathogenesis of amyloidosis secondary to AS and provided a new method for the accurate classification of AA amyloidosis.

objective To analyze the clinicopathological features and prognosis of antiglomerular basement membrane(GBM)disease,and evaluate the efficacy and safety of double filtration plasmapheresis(DFPP). Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study.All the patients were divided into 3 groups according to the manifestations at admission.Group Ⅰ∶24 patients with severe pulmonary hemorrhage or rapidly progressive glomerulonephritis(RPGN)received pulse methylprednisolone with or without DFPP,and then followed by prednisone and CTX.Group Ⅱ∶5 patients without severe pulmonary hemorrhage and RPGN received prednisone and CTX.Group Ⅲ∶5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy.Anti-GBM antibody titer of pre-and post-DFPP in 4 patients was measured consecutively,and removal rate was calculated.Results The mean age of all the patients was(41.1±16.6)years.Sixteen patients(45.7%)presented Goodpasture's syndrome.Eighteen patients(51.4%)had anti-GBM glomerulonephritis alone,whereas one suffered solely from pulmonary hemorrhage.20%patients had positive P-ANCA serology.54.2%crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients.Patients in Group Ⅰ showed more severe manifestation at admission:higher Scr level,higher titer of anit-GBM antibody,greater percentage of crescents.Within the follow-up period,7 patients died and kidneys of 50%patients survived.No patient died in Group Ⅱ and Ⅲ.The elder age,anemia,higher Scr(＞300 μmol/L),oliguria or anuria,emergency hemodialysis at admission,and more glomerular sclerosis were predictors of poor prognosis.The anti-GBM antibody was negative after 4 to 6 sessions of DFPP.and the mean removal rate was 55%.During total 94 DFPP sessions,there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations.DFPP is an effective and safe clearance way of anti-GBM antibody.

To conduct the characterization of its pharmacokinetics in rats of nifedipine sustained-release pellets and to study the relationship between the pellets and CYP3A4 activity. A gradient HPLC method was developed to simultaneously determine 6β-hydroxycortisol and hydrocortisone. CYP3A4 activity of rats was quantified by urinary ratio of 6β-hydroxycortisol/hydrocortisone after intravenous injection of hydrocortisone as a biomarker. HPLC method was also developed to quantify the drug concentration in plasma of rats, and the studies of pharmacokinetics were performed after oral administration of single dose of two formulations: Nifedipine matrix sustained-release pellets and nifedipine tablet(using as control). The results showed that the ratio of ten rats was 0. 271±0. 129. cmax of nifedipine sustained-release pellets decreases by nearly 70%, tmax significantly increased by 400% and t1/2 and MRT significantly increased by 230% compared to control. Nifedipine sustained-release pellets had a significant sustained-release property compared to the control and CYP3A4 activity affected its pharmacokinetics behavior.

Objective:To explore the effect of improving oral care based on cluster management in ventilator-associated pneumonia (VAP).Methods:Totally 126 VAP patients from February 2019 to February 2020 in our hospital were selected. The patients admitted from February 2019 to August 2019 were the control group, and the patients from September 2019 to February 2020 were the observation group, 63 cases in each group. The control group was treated with cluster nursing, and the observation group was treated with cluster nursing with improved oral care. The EICU hospitalization time, mechanical ventilation time, plaque index, pathogen infection, oral cleaning score, oral bleeding ulcer and aspiration were compared between the two groups.Results:After nursing, the EICU hospitalization time and mechanical ventilation time in the observation group were (18.34±4.15), (8.56±2.14) days, which were shorter than (23.56±4.82), (12.04±3.10) days in the control group ( t value was -6.514, -7.333, P<0.05). During the nursing process, the incidence of bleeding ulcer and aspiration in the observation group were 12.70% (8/63), 6.35% (4/63), which were lower than 30.16% (19/63), 20.63% (13/63) in the control group ( χ 2 values were 5.704, 5.508, P<0.05). After nursing, the plaque index of the two groups was lower than that before nursing ( t values were 12.516, 6.654, P<0.05), and the plaque index of the observation group was lower than that of the control group ( t value was -6.860, P<0.05). During the nursing process, the incidence of pathogenic bacteria infection in the observation group was 28.57% (18/63), which was lower than 49.21% (31/63) in the control group ( χ 2 value was 5.644, P<0.05). After nursing, the oral cleaning score of the two groups was lower than that before nursing ( t values were 11.118, 6.240, P<0.05), and the score of the observation group was (14.38±3.60) points, which was lower than (18.20±4.11) points of the control group ( t value was -5.549, P<0.05). Conclusion:Auricular pressure therapy can effectively improve the constipation symptoms, shorten the time required to take effect for the main symptoms, and improve the quality of life of schizophrenic patients.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep breathing disorder caused by obstruction of the upper airway during sleep from various causes. At present, the diagnosis and treatment of OSAHS are insufficient. OSAHS causes cognitive decline due to excessive oxidative stress and inflammatory response caused by sleep breathing disorder, and its alteration of the brain gray matter area may be related to cognitive dysfunction. This review investigates the correlation between cognitive dysfunction and brain gray matter areas changes in OSAHS, and elucidates the underlying mechanisms, which provide a theoretical basis for early clinical diagnosis and treatment.

A lung diffusion function detection system is designed. Firstly, the controllable collection of air, test gas source and calibration gas source was based on single-breath method measurement principle. Secondly, pulmonary diffusing capacity for carbon monoxide (D_lCO) was calculated by gas concentration measured by the non-dispersive infrared sensor to measure, the gas flow measured by the differential pressure sensor, and the temperature, humidity and atmospheric pressure sensors to test and evaluate the quantitative detection and evaluation of lung diffusion function. Moreover, a preliminary verification of the lung diffusion function detection system was implemented, and the results showed that the error of the lung carbon monoxide diffusion and the alveolar volume did not exceed 5%. Therefore, the system has high accuracy and is of great value for early screening and accurate assessment of COPD.
Carbon Monoxide ; Lung ; Pulmonary Diffusing Capacity/methods*

【Objective】 To study the therapeutic effect of autologous platelet-rich plasma(PRP) on joint injury. 【Methods】 Selected patients with joint injury treated in the Department of Transfusion Medicine of General Hospital of Southern Theatre Command of PLA from 2019 to 2020 were enrolled as the research objects, including 5 patients with shoulder joint injury, 34 patients with knee joint injury and 9 patients with ankle joint injury. All patients were treated with PRP injection at the injury site. The functional score and VAS score before and after treatment were compared. 【Results】 After 6 months of treatment, the CMS score and VAS of 5 patients with shoulder joint injury after treatment were (83.00±5.39) and (1.60±0.40), better than those before treatment (60.00±7.58)and (4.20±0.49)(P<0.05); The Lysholm knee score and VAS of 34 patients with knee joint injury after treatment were (80.73±2.43) and (2.07±0.24), better than those before treatment(50.30±2.96) and (4.28±0.33) (P<0.05); The AOFAS Ankle Hindfoot Scale and VAS of 9 patients with ankle joint injury after treatment were (68.44±4.59) and (2.56±0.53), better than those before treatment (42.67±4.57) and (4.89±0.63) (P<0.05). 【Conclusion】 For common joint injury sites, the clinical effect of using PRP injection is significant, which can effectively relieve pain and improve motor function, which is worthy of clinical application.

BACKGROUNDHuman myxovirus resistant protein A (MxA), encoded by the myxovirus resistance 1 (Mx1) gene, is an interferon (IFN)-triggered dynamin-like multi-domain GTPase involved in innate immune responses against viral infections. Recent studies suggest that MxA is associated with several human cancers and may be a tumor suppressor and a promising biomarker for IFN therapy. Mx1 gene mutations in the coding region for MxA have been discovered in many types of cancer, suggesting potential biological associations between mutations in MxA protein and corresponding cancers. In this study, we performed a systematic analysis based on the crystal structures of MxA and elucidated how these mutations specifically affect the structure and therefore the function of MxA protein.

METHODSCancer-associated Mx1 mutations were collected and screened from the COSMIC database. Twenty-two unique mutations that cause single amino acid alterations in the MxA protein were chosen for the analysis. Amino acid sequence alignment was performed using Clustal W to check the conservation level of mutation sites in Mx proteins and dynamins. Structural analysis of the mutants was carried out with Coot. Structural models of selected mutants were generated by the SWISS-MODEL server for comparison with the corresponding non-mutated structures. All structural figures were generated using PyMOL.

RESULTSWe analyzed the conservation level of the single-point mutation sites and mapped them on different domains of MxA. Through individual structural analysis, we found that some mutations severely affect the stability and function of MxA either by disrupting the intra-/inter-molecular interactions supported by the original residues or by incurring unfavorable configuration alterations, whereas other mutations lead to gentle or no interference to the protein stability and function because of positions or polarity features. The potential clinical value of the mutations that lead to drastic influence on MxA protein is also assessed.

CONCLUSIONSAmong all of the reported tumor-associated single-point mutations, seven of them notably affect the structure and function of MxA and therefore deserve more attention with respect to potential clinical applications. Our research provides an example for systematic analysis and consequence evaluation of single-point mutations on a given cancer-related protein.

Amino Acid Sequence ; Cell Transformation, Neoplastic ; genetics ; Crystallography, X-Ray ; Databases, Genetic ; Humans ; Myxovirus Resistance Proteins ; genetics ; Neoplasm Proteins ; genetics ; Neoplasms ; genetics ; Point Mutation ; Protein Domains ; genetics ; Protein Folding ; Sequence Alignment ; Stereoisomerism ; Structure-Activity Relationship