Osteoarthritis (OA) is the most common degenerative joint disease. Its pathological process is related to inflammatory response, chondrocyte apoptosis, and cartilage degeneration. Hippo-yes-associate protein(YAP) signaling pathway plays an important role in mediating organ size and tissue homeostasis. In recent years, the key effector protein YAP in the Hippo-YAP pathway has become a research hotspot in osteoarthritis. This article introduces the activation process of Hippo-YAP signaling pathway and the biological role of YAP. It reviews the progress of YAP in regulating osteoarthritis by influencing the proliferation and differentiation of mesenchymal stem cells and the proliferation, differentiation, and apoptosis of articular chondrocytes. It analyzed the problems encountered in YAP research in OA, introduces the research potential of YAP in other orthopedic diseases, and provides new ideas for subsequent research in Osteoarthritis.
Osteoarthritis/metabolism* ; Humans ; Signal Transduction ; Protein Serine-Threonine Kinases/physiology* ; Hippo Signaling Pathway ; YAP-Signaling Proteins ; Adaptor Proteins, Signal Transducing/physiology* ; Animals ; Transcription Factors ; Chondrocytes/cytology* ; Cell Cycle Proteins

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective:To observe the clinical efficacy and influence of modified Chaihu Shugansan combined with ursodeoxycholic acid tablets on inflammatory factors in treatment of chronic cholecystitis cholelithiasis （stagnation of liver and gallbladder Qi）. Method:One hundred and ten patients were randomly divided into control group （60 cases） and observation group （60 cases）. Both groups received lifestyle intervention， and oral ursodeoxycholic acid tablets， 50 mg/time， taken in the morning and evening meals. Patients in control group additionally took Yidanshu capsules orally， 4 capsules/time， 3 times/day. Patients in observation group additionally took modified Chaihu Shugansan orally， 1 dose/day. The treatment courses continued 3 months in both groups. Before and after treatment， traditional Chinese medicine （TCM） symptom scores were graded， the ultrasound status of chronic gallbladder inflammation， gallbladder contraction function and stones was graded， the levels of interleukin-6 （IL-6）， IL-8， tumor necrosis factor-α （TNF-α） and nuclear transcription factor-κB（NF-κB）Were detected， and safety was evaluated. The efficacy for TCM syndromes， imaging efficacy and the efficacy for eliminating gallbladder stones were compared between the two groups. Result:The efficacy for TCM syndrome， efficacy on color ultrasound for chronic cholecystitis and the efficacy on imaging for cholelithiasis in the observation group were all better than those in the control group（Z=2.104，Z=2.076，Z=2.101，P<0.05）. The thickness of gallbladder wall and volume of the gallbladder of the observation group were smaller than those of the control group （P<0.01）， and gallbladder contraction function was higher than that in control group （P<0.01）. Levels of IL-6， IL-8， TNF-α and NF-κB in observation group were lower than those in control group （P<0.01）. Conclusion:modified Chaihu Shugansan combined with ursodeoxycholic acid in the treatment of chronic cholecystitis and cholelithiasis （liver and gall Qi stagnation） is better than Yidanshu capsule combined with ursodeoxycholic acid sour scheme in terms of clinical efficacy， imaging efficacy， and elimination of gallbladder stones. It can reduce inflammation， and enhance gallbladder contraction， with high safety in clinical use.

Prohibitin (PHB), an evolutionarily conserved mitochondrial inner membrane protein, is highly expressed in cells that require strong mitochondrial function. Recently, we demonstrated that the deletion of Phb in spermatocytes results in impaired mitochondrial function. In addition, PHB expression in the mitochondrial sheath of human sperm has a significantly negative correlation with mitochondrial reactive oxygen species levels, but a positive one with mitochondrial membrane potential and sperm motility. These results suggest that mitochondrial PHB expression plays a role in sperm motility. However, the mechanism of PHB-mediated regulation of sperm motility remains unknown. Here, we demonstrate for the first time that PHB interacts with protein kinase B (AKT) and exists in a complex with phospho-PHB (pT258) and phospho-AKT in the mitochondrial sheath of murine sperm, as determined using colocalization and coimmunoprecipitation assays. After blocking AKT activity using wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), murine sperm have significantly ( P < 0.05) decreased levels of phospho-PHB (pT258) and the total and progressive motility. Furthermore, significantly ( P < 0.05) lower levels of phospho-PI3K P85 subunit α+γ (pY199 and pY467) and phospho-AKT (pS473; pT308) are found in sperm from infertile asthenospermic and oligoasthenospermic men compared with normospermic subjects, which suggest a reduced activity of the PI3K/AKT pathway in these infertile subjects. Importantly, these sperm from infertile subjects also have a significantly ( P < 0.05) lower level of phospho-PHB (pT258). Collectively, our findings suggest that the interaction of PHB with AKT in the mitochondrial sheath is critical for sperm motility, where PHB phosphorylation (pT258) level and PI3K/AKT activity are key regulatory factors.

OBJECTIVE: By recording the treatment events of implantable cardioverter defibrillator(ICD) in patients with ejection fraction reduced heart failure(HFrEF), to analyze the difference in primary and secondary prevention patients. METHODS: A single center retrospective study was conducted. HFrEF patients with ICD or cardiac resynchronization therapy with cardioverter defibrillator(CRT-D) implanted in Peking Union Medical College Hospital from January 2006 to December 2017 were enrolled in our study. Basic clinical data was collected and ICD treatment events were recorded during follow-up. The appropriate treatment events were identified according to electrocardiogram recorded by ICD. The ICD treatment events of primary and secondary prevention patients were analyzed. RESULTS: 1) A total of 145 patients with HFrEF implanted with ICD or CRT-D were enrolled, 103 primary prevention patients and 42 secondary prevention patients. Primary prevention patients had longer left ventricular end-systolic diameter(LVESD) and lower left ventricular ejection fraction(LVEF) than secondary prevention patients. 2) Multivariate competitive risk regression analysis showed that secondary prevention patients and male patients had higher risk of receiving appropriate treatment and appropriate shock therapy. 3) K-M curve and Log-Rank test showed that there was no significant difference in the risk of inappropriate treatment between primary and secondary prevention patients. The main cause of inappropriate treatment was atrial flutter or atrial fibrillation. CONCLUSION: 1) Primary prevention patients have lower risk of receiving appropriate treatment and appropriate shock therapy than secondary prevention patients; 2) There is no significant difference between primary and secondary prevention patients in the risk of inappropriate treatment. The main cause of inappropriate treatment events is atrial flutter or atrial fibrillation.

OBJECTIVETo validate those obtained immunogenic membrane antigens candidate of human pancreatic cancer in the performed research.

METHODSIn the pre-studies, serum IgG purified from clinically collected sera of pancreatic cancer patients underwent immunoblot with human pancreatic cancer cell line SW1990 membrane protein, totally obtained 9 positive protein spots. Number 5 and 6 positive dots of immunoblot were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and peptide mass fingerprinting matching. The candidate membrane antigens were further validated in cell lines by RT-PCR and real-time PCR. RNA of human normal pancreatic tissue and pancreatic cancer tissue was extracted respectively, different gene expression level of prohibitin 2 was studied by real-time PCR.

RESULTSNumber 5 and 6 positive dots were identified as prohibitin 2 and prohibitin. RT-PCR and real-time PCR all showed that gene of prohibitin 2 and prohibitin were expressed in the human pancreatic cancer cell line SW1990, AsPc and P3 respectively, especially in P3 cell with highest expression (t = 7.442, P < 0.01). In addition, gene expression level of prohibitin 2 was significant higher in human pancreatic cancer than that of normal pancreatic tissue (t = 0.893, P < 0.01).

CONCLUSIONSProhibitin 2 and prohibitin are both differently expressed in the pancreatic cancer cell line SW1990, AsPc and P3. Prohibitin 2 is obvious highly expressed in human pancreatic cancer tissue. Prohibitin 2 and prohibitin might be the candidate immunogenic membrane antigens of human pancreatic cancer.

Antigens, Neoplasm ; genetics ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins ; genetics ; metabolism ; Pancreatic Neoplasms ; genetics ; immunology ; metabolism ; Proteomics ; methods ; Repressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.

METHODSTwenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.

RESULTSCompared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P < 0.01) and downregulate nonphosphorylated Cx43.

CONCLUSIONSLPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

Animals ; Anti-Arrhythmia Agents ; pharmacology ; Arrhythmias, Cardiac ; chemically induced ; metabolism ; physiopathology ; Connexin 43 ; metabolism ; Lysophospholipids ; adverse effects ; Oligopeptides ; pharmacology ; Rabbits

OBJECTIVETo verify the obtained immunogenic membrane antigens candidate of pancreatic cancer in the performed research.

METHODSPancreatic cancer cell line SW1990 membrane protein underwent immunoblot with serum IgG purified from clinically collected sera of 66 pancreatic cancer patients. Number 3 and number 8 positive dots of immunoblot were identified by MALDI-TOF mass spectrometry and peptide mass fingerprinting matching. The candidate membrane antigens were further validated in cell lines by RT-PCR, real-time PCR and Western blot, and their different expression level of gene and protein in pancreatic cancer cell lines were contrastly studied.

RESULTSNumber 3 and number 8 positive dots were identified as: voltage-dependent anion channel (VDAC3) and catechol-o-methyltransferase (COMT). RT-PCR, real-time PCR and Western blot showed that gene and protein of VDAC3 and COMT were expressed in the pancreatic cancer cell line SW1990, AsPc and P3 respectively.

CONCLUSIONVDAC3 and COMT might be the candidate immunogenic membrane antigens of human pancreatic cancer, and their gene and protein are differently expressed in the pancreatic cancer cell line SW1990, AsPc and P3.

Antigens, Neoplasm ; analysis ; Cell Line, Tumor ; Humans ; Pancreatic Neoplasms ; immunology ; Proteomics

Objective To investigate the prevalence of dentin hypersensitivity in Chinese urban adults aged between 20-69 years old and the factors related to dentin hypersensitivity.Methods The Chinese national survey on dentin hypersensitivity was conducted in 20-69 years old adults in six representative cities,Beijing,Shahghai,Guangzhou,Wuhan,Chengdu,and Xi'an in 2008.A muhi-stage stratified randomizing sampling method was used.Subjects were recruited from 36 urban survey sites in 6 cities. A structured questionnaire and a clinical examination on dentin hypersensitivity were used in the survey.The dentin hypersensitivity was diagnosed by a subject self-perceived short,sharp pain in resportse to a blast of cold air from a triple syringe administered to a tooth surface in 1 cm. Results In total,7939 twenty to sixty-nine years old subjects completed a structured interview and underwent a clinical examination on dentin hypersensitivity.Among them,40.7%(3230/7939) of the subjects reported being suffered from teeth sensitivity. When confirmed using a blast of air from a triple syringe and by ruling out other causes of sensitivity,such as caries,the prevalence was 29.7% (2354/7939),and the mean number of sensitive teeth was 1.4.The highest prevalence of dentin hypersensitivity[39.1%(622/1592)]was found in 50-59 years old group.The commonest teeth affected were the premolar teeth and the commonest initiating factor was cold drinks.Female,low education level,with gingival recession,attachment loss,and with the history of acidic substances derived from the stomach was related to dentin hypersensitivity.Conclusions Dentin hypersensitivity was comnlon in 20-69 years old Chinese urban adults.Dental professionals should give further emphasis to it.

OBJECTIVETo screen the peptides that bind specifically to the hepatoma cells using phage display random peptides library.

METHODSThree rounds of panning were conducted in vitro targeting HepG2 cell lines. In nude mice bearing HepG2 tumor, one round of panning was conducted, and 30 phage clones were randomly selected for sequence analysis to identify the consensus sequence. Immunocytochemistry and immunohistochemistry were performed to determine the specificity of the phages to the hepatoma cells.

RESULTSAfter three rounds of panning in vitro and one round of panning in vivo, the phages binding to HepG2 cells were enriched. Sequence analysis of the randomly selected clones identified the peptide sequence VRKRSECLGAHD as the most frequent sequence. Immunocytochemistry and immunohistochemistry confirmed the specificity of the phage binding to the hepatoma cells.

CONCLUSIONSSpecific peptides against hepatoma cells can be obtained from a phage- display peptide library, which provides an experimental basis for developing therapeutic agents targeting hepatoma cells.

Animals ; Carcinoma, Hepatocellular ; metabolism ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; Mice ; Neoplasm Transplantation ; Peptide Library ; Peptides ; isolation & purification ; metabolism ; Protein Binding