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Objective:To optimize the preparation conditions and methods of Al 18F-prostate specific membrane antigen (PSMA)-11 and evaluate the feasibility of clinical transformation. Methods:PSMA- N, N′-bis(2-hydroxy-5-(carboxyethy)benzyl)ethylenediamine- N, N′-diacetic acid (HBED-CC) dissolved in CH 3COONH 4 buffer (pH=4.8) was reacted with AlCl 3·3H 2O dissolved in pure water at a molar ratio of 1∶1 (60 ℃, 10 min), and then purified by tC18 column and freeze-dried to obtain [Al]-PSMA-11. [Al]-PSMA-11 was labeled by 18F - and the effects of reaction temperature and pH value on the labeling rate were investigated. The labeled products were purified by tC18 column and filtered through sterile filter to obtain Al 18F-PSMA-11. The comparison of biodistribution between Al 18F-PSMA-11 and 68Ga-PSMA-11 was analyzed on 5 healthy volunteers (age (56±8) years). The differences of SUV max between two groups were analyzed by independent-sample t test. Besides, the early and delayed imaging of Al 18F-PSMA-11 PET/CT were performed on a patient (70 years old) with recurrent prostate cancer for assessment of its potential for prostate cancer recurrence monitoring. Results:The labeling rate was (42.3±3.2)% reacting in aqueous phase (60 ℃, pH=4.8) for 15 min. After being purified with tC18 cartridge, the radiochemical purity of the product was still more than 95% after placement at room temperature for 3 h. Preliminary application demonstrated that there was no significant difference in the biodistribution of Al 18F-PSMA-11 and 68Ga-PSMA-11 among lacrimal gland, parotid gland, submandibular gland, liver, spleen, kidney, bladder and part of intestine and SUV max of targeted organs were also not different ( t values: 0.19-1.95, all P>0.05) between two groups. Multiple bone metastases were observed by Al 18F-PSMA-11 PET/CT delayed imaging (3 h) in a patient with recurrent prostate cancer. Conclusion:Al 18F-PSMA-11 produced with pre-conjugated [Al]-PSMA-11 meets the requirement of the PET imaging application, and it has good potential of localization and imaging for prostate cancer metastatic lesions.
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Argininemia is a rare autosomal recessive inherited disease, characterized by complex and diverse clinical symptoms.Its pathogenesis remains unclarified.The oligodendrocytes and neuro injury caused by energy meta-bolism disorders may account for neurosystem damage.The basic treatment methods for argininemia are the low-protein diet and nitrogen scavenger, which, however, cannot effectively prevent the progress of the neurological damage.Enzyme replacement or gene therapy is an ideal regimen for argininemia.However, gene editing therapy has not been applied in clinical practice.Liver transplantation (LT) is currently a practical option for argininemia treatment.Although LT cannot repair genetic defects in patients, but it can supplement arginase I, normalize plasma arginine and its metabolites, prevent progressive damage, relieve neurological symptoms, and improve the patients quality of life.For the low incidence of argininemia, it is not fully understood.In this paper, the clinical characteristics, pathogenesis, diagnosis, and treatment of argininemia were reviewed, in order to further more people′s understanding of this disease.
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Objective:To study the effect of microRNA (miR)-330-3p on hepatic ischemia-reperfusion injury (IRI) in mice, meanwhile, and to determine potential molecular mechanism.Methods:Eighty male C57BL/6 mice, aged 7-8 weeks, 23-25 g, specific pathogen free, were randomly divided into 8 groups (10 mice in each group) using random number table: reperfusion 2 h group, 6 h group, 12 h group, 24 h group, sham group, miR-330-3p agomir group (preoperative injection of agonist), miR-330-3p antagomir group (preoperative injection of inhibitor) and miRNA-NC group. Except for the sham group, the hepatic IRI model were established in mice. Polymerase chain reaction (PCR), Western blot and immunohistochemistry were used to detect the expression of miR-330-3p and phosphoglycerate mutase family member 5 (PGAM5), cleave caspase-1 and GSDMD. Luciferase reporter assay was performed to investigate whether miR-330-3p directly targets PGAM5. At the same time, AML12 cells were also treated with miR-330-3p mimics/inhibitor or PGAM5 siRNA, then the expression of PGAM5, NLRP3, cleave caspase-1 and GSDMD were detected by Western blot analysis.Results:Level of miR-330-3p gradually decreased after reperfusion, however, mRNA level of PGAM5 was increased thereafter ( P<0.05) as compared with the sham group. Serum level of AST and ALT were decreased in miR-330-3p agomir group while that of were increased in miR-330-3p antagomir group as a function of time following reperfusion, and the differences were statistically significant (all P<0.05). Cleave caspase-1 expression was decreased in miR-330-3p agomir group but was increased in miR-330-5p antagomir group ( P<0.05). Luciferase reporter assay was performed to determine PGAM5 was a target gene of miR-330-3p. SiRNA-mediated knockdown of PGAM5 decreased level of GAM5 (0.24±0.09), NLRP3(0.12±0.07), cleave caspase-1 (0.15±0.07) and GSDMD (1.08±0.08) as compared with the siRNA-NC group (1.17±0.14), (0.36±0.09), (0.68±0.09), (1.36±0.08), and the differences were statistically significant (all P<0.05). Conclusion:MiR-330-3p can alleviate hepatic IRI in mice, which may be related to inhibition of PGAM5-induced pyroptosis.
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Lung cancer has become the leading cause of death from malignant tumors worldwide. At the same time, statistics show that the incidence and mortality of lung cancer are increasing year by year. Because patients with lung cancer do not have typical symptoms in the early stage, this directly leads to the majority of patients who are already at advanced stage at the time of diagnosis, and the prognosis is not good. How to diagnose lung cancer early and accurately and find patients with potential risks and predict the prognosis is of great significance for the formulation of further treatment plans. In recent years, the field of artificial intelligence has been booming. As a branch of artificial intelligence, machine learning could learn efficiently from complex and large amounts of data. Besides, the learned model has good generalization ability. These characteristics can take greatly advance on the research about lung cancer
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The aim of our study was to explore the relationship between the methylation status of the alpha-1A adrenergic receptor (ADRA1A) gene and hepatocellular carcinoma (HCC). We combined our in-house data-set with the Cancer Genome Atlas (TCGA) data-set to screen and identify the methylation status and expression of adrenergic receptor (AR) genes in HCC. Immunohistochemistry and western blot were performed to assess the expression of ADRA1A in HCC cell lines and tissues. We further evaluated the methylation levels of the ADRA1A promoter region in 160 HCC patients using the Sequenom MassARRAY® platform and investigated the association between methylation of ADRA1A and clinical characteristics. The expression levels of ADRA1A mRNA and protein were significantly decreased in HCC tissues. Compared with that in paired normal tissues, the mean methylation level of the ADRA1A promoter region was significantly increased in tumour tissues from 160 HCC patients (25.2% vs. 17.0%, P < 0.0001). We found that a DNA methyltransferase inhibitor (decitabine) could increase the expression of ADRA1A mRNA in HCC cell lines. Moreover, hypermethylation of the ADRA1A gene in HCC samples was associated with clinical characteristics, including alcohol intake (P = 0.0097) and alpha-fetoprotein (P = 0.0411). Receiver operator characteristic (ROC) curve analysis demonstrated that the mean methylation levels of ADRA1A could discriminate between HCC tissues and adjacent non-cancerous tissues (AUC = 0.700, P < 0.0001). mRNA sequencing indicated that the main enriched pathways were pathways in cancer, cytokine-cytokine receptor interaction and metabolic pathways (P < 0.01). ADRA1A gene hypermethylation might contribute to HCC initiation and is a promising biomarker for the diagnosis of HCC.
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Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , DNA Methylation , Liver Neoplasms/genetics , Receptors, Adrenergic, alpha-1/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/pathology , Epigenesis, Genetic , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Hep G2 Cells , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Promoter Regions, GeneticABSTRACT
Objective:In response to the outbreak of severe infectious diseases such as new coronavirus pneumonia, an artificial intelligence based image diagnosis system is established to improve the efficiency of disease diagnosis, reduce the burden of front-line doctors, and improve the medical resource allocation.Methods:Using the deep convolution neural network and regional prevention and control auxiliary information system, the image data and other information of the confirmed patients were analyzed and processed comprehensively.Results:A set of AI based medical image auxiliary data processing system is proposed. Combined with multimodal medical data collaborative diagnosis, it can effectively and accurately segment the diseased areas in patients' lung CT images, and generate standardized reports. Relying on the multi-center collaborative diagnosis and treatment platform, the system can introduce multi-expert remote consultation mechanism to improve the diagnosis quality of severe patients.Conclusions:By segmenting pathological regions, generating standardized reports and introducing multicenter mechanism, the system can help to optimize the medical resources allocation and improve the utilization of these resources.
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Objective@#In response to the outbreak of severe infectious diseases such as new coronavirus pneumonia, an artificial intelligence based image diagnosis system is established to improve the efficiency of disease diagnosis, reduce the burden of front-line doctors, and improve the medical resource allocation.@*Methods@#Using the deep convolution neural network and regional prevention and control auxiliary information system, the image data and other information of the confirmed patients were analyzed and processed comprehensively.@*Results@#A set of AI based medical image auxiliary data processing system is proposed. Combined with multimodal medical data collaborative diagnosis, it can effectively and accurately segment the diseased areas in patients' lung CT images, and generate standardized reports. Relying on the multi-center collaborative diagnosis and treatment platform, the system can introduce multi-expert remote consultation mechanism to improve the diagnosis quality of severe patients.@*Conclusions@#By segmenting pathological regions, generating standardized reports and introducing multicenter mechanism, the system can help to optimize the medical resources allocation and improve the utilization of these resources.
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BACKGROUND@# Stent failure is more likely in the lipid rich and thrombus laden culprit lesions underlying ST-segment elevation myocardial infarction (STEMI). This study assessed the effectiveness of post-dilatation in primary percutaneous coronary intervention (pPCI) for acute STEMI.@*METHODS@# The multi-center POST-STEMI trial enrolled 41 consecutive STEMI patients with symptom onset <12 hours undergoing manual thrombus aspiration and Promus Element stent implantation. Patients were randomly assigned to control group (n=20) or post-dilatation group (n=21) in which a non-compliant balloon was inflated to >16 atm pressure. Strut apposition and coverage were evaluated by optical coherence tomography (OCT) after intracoronary verapamil administration via thrombus aspiration catheter, post pPCI and at 7-month follow-up. The primary endpoint was rate of incomplete strut apposition (ISA) at 7 months after pPCI.@*RESULTS@# There were similar baseline characteristics except for stent length (21.9 [SD 6.5] mm vs. 26.0 [SD 5.8] mm, respectively, P=0.03). In post-dilatation vs. control group, ISA rate was lower (2.5% vs. 4.5%, P=0.04) immediately after pPCI without affecting final TIMI flow 3 rate (95.2% vs. 95.0%, P>0.05) or corrected TIMI frame counts (22.6±9.4 vs. 22.0±9.7, P>0.05); and at 7-month follow-up (0.7% vs. 1.8%, P<0.0001), the primary study endpoint, with similar strut coverage (98.5% vs. 98.4%, P=0.63) and 1-year rate of major adverse cardiovascular events (MACE).@*CONCLUSION@# In STEMI patients, post-dilatation after stent implantation and thrombus aspiration improved strut apposition up to 7 months without affecting coronary blood flow or 1-year MACE rate. Larger and longer term studies are warranted to further assess safety (ClinicalTrials.gov identifi er: NCT02121223).
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Objective To explore the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT related metabolic parameters for Kras mutation in colorectal cancer (CRC) patients.Methods Retrospective analysis was conducted in 150 patients (105 males,45 females,median age:63 years) with CRC who underwent 18F-FDG PET/CT in Changhai Hospital of Navy Medical University between November 2011 and August 2017.The primary tumors were removed by surgery and patients received genetic testing within 1 month after PET/CT.18F-FDG PET/CT related metabolic parameters were measured,including maximum standardized uptake value (SUVmax),metabolic tumor volume (MTV;including MTV2.5,MTV20%,MTV30%,MTV40%,MTV50%),total lesion glycolysis (TLG;including TLG2.5,TLG20%,TLG30%,TLG40%,TLG50%).Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were used to analyze the data.Results There were 78 Kras-mutated type patients and 72 wild-type patients.Logistic regression analysis showed that SUVmax (odds ratio (OR) =1.176,95% CI:1.043-1.327) and MTV2.5 (OR =1.125,95 % CI:1.002-1.263) were predictors of Kras mutation.With SUVmax =15.5 and MTV2.5 =23.79 cm3 as the cut-off value,the prediction accuracies of Kras mutation were 67.33%(101/150) and 65.33%(98/150),respectively.The accuracies of SUVmax and MTV2.5 for predicting Kras mutation were higher in recta or sigmoid colon cancers (70.79%(63/89) and 68.54%(61/89)).Conclusion SUVmax and MTV2.5 can predict Kras mutation in CRC patients,but there is a significant gap of predictive efficiency between PET/CT and gene detection.
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Objective To analyze the main practices of capitation payment system reform in the case areas and put forward enlightenments and suggestions in this regard. Methods The implementation practices of the case areas were summarized, and descriptive statistical analysis was carried out on the implementation effects. Results By analyzing the effectiveness of the case areas′reform, it was found that the case areas are curbing the excessive growth of medical expenses (for example, outpatient fees per visit of Dingyuan county-level hospitals decreased from 245.11 yuan in 2015 to 218.40 yuan in 2017), increasing the actual compensation ratio of residents ( for example, the actual compensation ratio of Funan increased from 59.80% in 2015 to 63.28% in 2017), forming a medical treatment pattern within the county (for example, out-of-county compensation ratio in Dingyuan decreased from 37.38% in 2015 to 31.13% in 2017), achieving double-way referrals (for example, the number of referrals to superior hospitals of Jimo increased from 98 in 2015 to 328 in 2017), improving the subsidence of quality services, and controlling the risks of medical insurance funds. Conclusions At present, the reform of the case areas has been implemented steadily and achieved results. It is recommended to further improve such aspects as reform coordination, insurance standard setting, incentive mechanism establishment, and leadership to ensure the reform progress.
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Pilot areas have achieved initial success in capitation reform. On the other hand, challenges remain unsolved in terms of practical pathways, change of national medical insurance management system, related measures, incentives and allocative mechanism for implement of the reform. With the concerning on progress, practice, effects and challenges of typical areas, this article established an institutional framework. On such basis, we propose to design and refine a scheme in terms of 5 aspects, namely strengthening the basic medical care packages′financing, setting contents and standard of the basic medical care packages rationally, establishing effective evaluation system and formulating supporting measures.
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Objective To evaluate the impacts of DRGs payment reform on patients, medical insurance fund and hospitals, then to steadily promote the payment reform. Methods The reimbursement data of inpatients covered by NCMS yet beyond the single-disease payment were collected from two DRGs pilot hospitals from January 2016 to June 2018. Such means as descriptive statistics, t test and method of interrupted time series analysis were used to compare the changes found in the average out-of-pocket payment, actual reimbursement rate, average per-hospitalization compensation, average length of stay, and average hospitalization expense before and after the DRGs payment reform. Results After the reform, the average out-of-pocket payment and average length of stay began to fall slightly instead of the increasing trend (β3 were -72.79,-0.11, respectively, and P<0.01), the upward trend of average hospitalization expense slowed down ( β3 was -113. 55, and P<0.01), actual reimbursement rate and the average per-hospitalization compensation stayed the original growth trend (β3 were 0.10,-31.15, respectively, and P values were 0.08, 0.09, respectively). Conclusions DRGs encourages the hospitals to curb the average hospitalization expenses, with the growth trend kept at a slower pace. The payment reform does not increase the financial burden of patients, and tends to ease such pressure on funds, but the long-term effect remains to be seen.
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@#Objective:To study the molecular biology mechanisms of Wistar rats after spinal cord injury, and find out key microRNAs. Methods:A total of 15 Wistar rats were divided into control group (<italic>n</italic> = 3) and spinal cord injury group (<italic>n</italic> = 12). The latter group was divided into four hours, three days, seven days and 14 days subgroups, with three rats in each subgroup. Microarray 3.0 was used to investigate microRNA expression profiles of Wistar rats with spinal cord injury. Bioinformatics was used to predict microRNAs playing key regulatory roles, and to predict target genes. Reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) was applied to detect the expression of miR-20a-3p. Western blotting was employed to detect the signal transducer and activator of transcription (STAT) 3 level. The correlation between target protein and microRNA expression trend in each group was analyzed. The key microRNA was inhibited in the neurons. The relationship between target protein expression and axon growth was observed with immunofluorescence. Results:In the rats with spinal cord injury, totally 658 microRNAs had changed at least once. In all the altered microRNAs, miR-20a-3p was upregulated obviously. It predicted that the target gene of miR-20a-3p was STAT3 via application of bioinformatics analysis. The expression trend of STAT 3 and miR-20a-3p in spinal cord was opposite. After the inhibition of miR-20a-3p, the expression of STAT3 in neurons was unregulated and axonal growth was extended. Conclusion:The upregulation of miR-20a-3p leads to downregulation of STAT3, and miR-20a-3p is one of the key targets in the treatment of spinal cord injury.
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Objective To investigate the role of Th22 cells and interlukin 22(IL-22) secreted by Th22 cells in the development of breast cancer. Methods The breast cancer model was established by in situ inoculation of 4T1 breast cancer cells in mice. The experimental group (20 cases) was injected with phosphoric acid buffer (PBS) 0.1 ml containing 4105 4T1 cells into the breast fat pad of mice, while the control group (20 cases) was injected with PBS 0.1 ml into the breast fat pad of mice without cells. Flow cytometry was used to detect Th22 cells in peripheral blood and enzyme linked immunosorbent assay (ELISA) was used to detect the level of IL-22 in serum. The difference of IL-22 levels between Th22 cells and serum was compared between the two groups, and the correlation between Th22 cells and IL-22 was analyzed. Real-time fluorescence quantitative PCR was used to detect the expression of IL-22. The phosphorylation of STAT3 in 4T1 cells treated with IL-22 was detected by Western blot. Results Tumors grew one week after in situ inoculation, and the expression of Th22 cells and IL-22 in serum was significantly increased and positively correlated with that in control group (r=0.569, P<0.01 or <0.05). The level of IL-22 mRNA in tumor group was significantly increased compared with that in normal group:(22.28 ± 2.52) ng/L vs. (18.92 ± 1.80) ng/L (P<0.01), and STAT3 was phosphorylated by 4T1 cells after IL-22 treatment. Conclusions Th22 cells and cytokines IL-22 secreted by them can promote the occurrence and development of breast cancer by affecting STAT3 phosphorylation.
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OBJECTIVE: Our study aimed to investigate glucose and lipid level as well as insulin resistance (IR) in patients with polycystic ovary syndrome (PCOS). METHODS: In a case-control study, 426 patients with PCOS were diagnosed according to Rotterdam criteria, and they were conducted in the morning after a 10-h fast. Participants received standard 75-g oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were obtained at 0, 30, 60, 120, and 180 min. They also received the lipid evaluation; 95 healthy women with normal menstrual cycles served as controls. Thus, by modifying the homeostasis model assessment of insulin resistance (HOMA-IR) with the use of individual time-course values of glucose and insulin plasma levels, we developed a new assessment method, HOMA-Mx. RESULTS: In our study, 23.71% of patients had abnormal glucose metabolism. With further impairment in glucose metabolism, the glucose and lipid level gradually increased (P<0.05), while the impaired glucose regulation (IGR) group showed greater insulin response than a type 2 diabetes mellitus (T2DM) group. Compared with healthy controls, both lean and obese PCOS patients with normal glucose tolerance (NGT) had a higher body mass index (BMI), and higher serum glucose, insulin, and lipid values. Additionally, the insulin value peaked at 30 min and 60 min in the lean and obese groups, respectively. HOMA-M30 proved to be the best predictive parameter (cutoff: 20.36, area under the curve [AUC]: 0.753) for assessment of IR in normal-weight patients and HOMA-IR (cutoff: 32.17, AUC: 0.868) was optimal in obese PCOS patients. CONCLUSIONS: A new assessment method was developed for these groups: HOMA-M30 for lean PCOS patients and HOMA-M60 for obese patients, in order to focus on peak insulin values for early detection of IR.
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Objective To analyze the operation of the diagnosis-related groups ( DRGs) pilots for inpatients in the new rural cooperative medical system in Yulin city of Shaanxi province. Methods The medical records of 33306 inpatients discharged from the 3 pilot hospitals between January and July in 2017 were analyzed, aided by expert discussions, on-site assessment and medical records examinations. Results By the end of July 2017, the DRGs grouping tool had been running stably. The DRGs enrollment rates of discharged inpatients were all up to 99% in the 3 pilot hospitals. The coefficient of variation ( CV) was higher than 1 only in a few DRGs. The average length of stay and the average hospitalization expenses growth rate were both found declined. However, there also exist problems in the pilots, namely incomplete regulations for DRGs, low clinical path coverage rate, hysteretic supervision and assessment, uneven quality of medical records management and so on. Conclusions The pilots operated smoothly as evidenced in their initial success. Yet the following recommendations were raised for the improvements: To strengthen the organization and leadership to improve the DRGs related supporting system in pilot hospitals; To strengthen the promotion and application of clinical paths for standardization of the medical service process;To improve the DRGs assessment program and establish DRGs operation monitoring and tracking analysis system; To strengthen the training of medical record coding staff to improve continuously the quality of medical records.
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The problems in traditional imaging film and its reporting process were described.A virtual printing server network and a self-service printing service model of image film and its reporting model,established by improving the traditional imaging film and reporting process,could shorten the waiting time of patients after examinations,reduce the errors in imaging film reports,and improve the working efficiency of staff.
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Objective To investigate the secondary metabolites from diethyl sulfate(DES)mutant 3d10-01 derived from Peni-cillium chrysogenum S-3-25. Methods The secondary metabolites were isolated by multiple separation techniques,such as silica gel,Sephadex LH-20 column chromatography and HPLC. The structures of the compounds were determined by ESI-MS and NMR spectroscopic data. The antitumor activity was assayed by the MTT method. HPLC-UV analysis was used to determine if compounds 1-7 were newly produced by the mutant. Results Seven secondary metabolites,including methyl 2,4-dihydroxy-3,5,6-trimethylbenzo-ate(1),6-hydroxymethyl-2,2-dimethylchromanone(2),regiolone(3),(3S,4S)-3,4-dihydro-3,4,8-trihydroxy(2H)naphthalenone (4),cerebroside C(5),cerebroside D(6)and dankasterone A(7),were isolated from the fermentation products of the mutant 3d10-01. Compounds 1,4 and 7 showed strong inhibitory effects on the five tested cell lines,but 2,3 and 6 only exhibited the proliferation of HL-60 cells to some extent. Compounds 1-4 and 7 were newly produced by the mutant 3d10-01. Conclusion Compounds 1-7 are firstly isolated from P. chrysogenum. The inhibitory effects on certain tested antitumor cell lines of compounds 1-4,6 and 7 are report-ed for the first time.
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Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
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Animals , Humans , Mice , Acid Phosphatase , Asian People , Bone Diseases, Metabolic , Bone Remodeling , Bone Resorption , Femur , Mice, Transgenic , Osteitis Deformans , Osteoblasts , Osteoclasts , Osteogenesis , Phosphorylation , Phosphotransferases , Tacrolimus Binding Proteins , Transcription FactorsABSTRACT
<p><b>BACKGROUND</b>Myocarditis is an inflammatory disease of the myocardium that may lead to cardiac death in some patients. However, little is known about the predictors of in-hospital mortality in patients with suspected myocarditis. Thus, the aim of this study was to identify the independent risk factors for in-hospital mortality in patients with suspected myocarditis by establishing a risk prediction model.</p><p><b>METHODS</b>A retrospective study was performed to analyze the clinical medical records of 403 consecutive patients with suspected myocarditis who were admitted to Ningbo First Hospital between January 2003 and December 2013. A total of 238 males (59%) and 165 females (41%) were enrolled in this study. We divided the above patients into two subgroups (survival and nonsurvival), according to their clinical in-hospital outcomes. To maximize the effectiveness of the prediction model, we first identified the potential risk factors for in-hospital mortality among patients with suspected myocarditis, based on data pertaining to previously established risk factors and basic patient characteristics. We subsequently established a regression model for predicting in-hospital mortality using univariate and multivariate logistic regression analyses. Finally, we identified the independent risk factors for in-hospital mortality using our risk prediction model.</p><p><b>RESULTS</b>The following prediction model for in-hospital mortality in patients with suspected myocarditis, including creatinine clearance rate (Ccr), age, ventricular tachycardia (VT), New York Heart Association (NYHA) classification, gender and cardiac troponin T (cTnT), was established in the study: P = ea/(1 + ea) (where e is the exponential function, P is the probability of in-hospital death, and a = -7.34 + 2.99 × [Ccr <60 ml/min = 1, Ccr ≥60 ml/min = 0] + 2.01 × [age ≥50 years = 1, age <50 years = 0] + 1.93 × [VT = 1, no VT = 0] + 1.39 × [NYHA ≥3 = 1, NYHA <3 = 0] + 1.25 × [male = 1, female = 0] + 1.13 × [cTnT ≥50 μg/L = 1, cTnT <50 μg/L = 0]). The area under the receiver operating characteristic curve was 0.96 (standard error = 0.015, 95% confidence interval [CI]: 0.93-0.99). The model demonstrated that a Ccr <60 ml/min (odds ratio [OR] = 19.94, 95% CI: 5.66-70.26), an age ≥50 years (OR = 7.43, 95% CI: 2.18-25.34), VT (OR = 6.89, 95% CI: 1.86-25.44), a NYHA classification ≥3 (OR = 4.03, 95% CI: 1.13-14.32), male gender (OR = 3.48, 95% CI: 0.99-12.20), and a cTnT level ≥50 μg/L (OR = 3.10, 95% CI: 0.91-10.62) were the independent risk factors for in-hospital mortality.</p><p><b>CONCLUSIONS</b>A Ccr <60 ml/min, an age ≥50 years, VT, an NYHA classification ≥3, male gender, and a cTnT level ≥50 μg/L were the independent risk factors resulting from the prediction model for in-hospital mortality in patients with suspected myocarditis. In addition, sufficient life support during the early stage of the disease might improve the prognoses of patients with suspected myocarditis with multiple risk factors for in-hospital mortality.</p>