What are the Risk Factors for Residual Pain After Percutaneous Vertebroplasty or Kyphoplasty? A Meta-Analysis.

BACKGROUND: Although many risk factors for residual pain following percutaneous vertebroplasty or kyphoplasty (PVP or PKP) have been reported in many studies, research methods and cohorts differ greatly. A previous meta-analysis identified patient- and operation-specific risk factors for residual pain. This study aimed to examine the available data and identify significant risk factors for residual pain after PVP or PKP. METHODS: PubMed, EMBASE, Web of Science, and the Chinese Wanfang Database were searched for relevant research in English and Chinese, and full-text publications including patients with and without residual pain were compared. Only studies presenting odds ratios from multivariate analysis of residual pain data were considered. To evaluate the impact of the results of the selected articles, Review Manager 5.4 was used. RESULTS: Twelve publications including a total of 3120 patients met the requirements. The meta-analysis examined 10 factors associated with residual pain and categorized them as either patient- or operation-associated factors. Thoracolumbar fascia injury, intravertebral vacuum cleft, depression, and number of fractured vertebrae were all significant patient-associated parameters for residual pain. Significant operation-associated risk factors included bone cement distribution and intraoperative facet joint injury. CONCLUSIONS: In this meta-analysis, we identified several significant risk factors for residual pain after PVP or PKP. These findings may be helpful for patient counseling and surgical planning.

Research for accurate auxiliary diagnosis of lung cancer based on intracellular fluorescent fingerprint information.

The distinctions in pathological types and genetic subtypes of lung cancer have a direct impact on the choice of treatment choices and clinical prognosis in clinical practice. This study used pathological histological sections of surgically removed or biopsied tumor tissue from 36 patients. Based on a small sample size, millions of spectral data points were extracted to investigate the feasibility of employing intracellular fluorescent fingerprint information to diagnose the pathological types and mutational status of lung cancer. The intracellular fluorescent fingerprint information revealed the EGFR gene mutation characteristics in lung cancer, and the area under the curve (AUC) value for the optimal model was 0.98. For the classification of lung cancer pathological types, the macro average AUC value for the ensemble-learning model was 0.97. Our research contributes new idea for pathological diagnosis of lung cancer and offers a quick, easy, and accurate auxiliary diagnostic approach.

Short-term effects of different PM2.5 ranges on daily all-cause mortality in Jinan, China.

To examine the effects of different PM2.5 concentration ranges on daily all-cause mortality, 8768 all-cause deaths were recorded in the database of the Shandong Provincial Hospital Affiliated to Shandong First Medical University. Data of air pollutants (PM2.5 and O3) concentration were provided by the Jinan Environment Monitoring Center. The relative risk of all-cause mortality was assessed using a quasi-Poisson regression model after adjusting for confounding factors. The concentrations of PM2.5 were divided into four ranges 0-35 µg/m3; 35-75 µg/m3; 75-115 µg/m3; 115-150 µg/m3. There was no significant relationship between PM2.5 exposure and all-cause deaths in individuals aged < 60 years. However, for individuals aged ≥ 60 years, there was a significant positive association between exposure concentrations and all-cause deaths within the ranges 0-35 µg/m3, 35-75 µg/m3, and 115-150 µg/m3 with a mortality increase of 1.07 (1.01, 1.13), 1.03 (1.00, 1.05), and 1.05 (1.01, 1.08), respectively. When the population aged ≥ 60 years was stratified into gender groups, exposure to PM2.5 in the range 0-35 µg/m3 increased the mortality risk in men but not women. All-cause mortality in women, but not men, increased significantly with exposure to PM2.5 in the ranges of 35-75, 75-115, and 115-150 µg/m3.

Pharmacokinetic Study of Frovatriptan Succinate Tablet After Single and Multiple Oral Doses in Chinese Healthy Subjects.

PURPOSE: The present report describes findings from a Phase I clinical study that evaluated the single- and multiple-dose pharmacokinetics of frovatriptan succinate tablet in Chinese healthy subjects. METHODS: A total of 24 healthy subjects were enrolled. In single-dose study, 2.5, 5, and 10 mg oral doses of frovatriptan succinate tablet were administrated. A 2.5 mg frovatriptan succinate tablet was administrated 12 times in 7 days in the multiple-dose study. Blood samples were collected at scheduled time points. RESULTS: The results in single-dose study indicated that the blood levels were proportional to the administered dose, with the mean Cmax and AUClast ranging from approximately 6.27 ng/mL-17.35 ng/mL and 92.52 h⋅ng/mL - 287.40 h⋅ng/mL over the dose range. In the multiple-dose study, moderate drug accumulation was noted, which was attributable to forvatriptan's long t1/2 of about 26.47 to 30.63 h. Gender differences were noticed in both single- and multiple-dose study; exposure PK parameters were consistently higher in female than in male. CONCLUSION: These pharmacokinetic evaluations in healthy Chinese subjects found that frovatriptan succinate tablet has an acceptable pharmacokinetic profile in Chinese subjects.

Impact of end-expiratory pressure fluctuation on tidal volume in the trilevel positive airway pressure mode.

INTRODUCTION: In noninvasive positive-pressure ventilation (NPPV), the changes in the expiratory positive airway pressure (EPAP) directly affect the magnitude of the tidal volume. OBJECTIVES: This experimental study aims to verify the precise effects of end-expiratory fluctuation on the body tidal volume to better assist NPPV in clinical practice. METHODS: We selected the TestChest-simulated lung simulation of different populations, including healthy subjects (normal group), patients with chronic obstructive pulmonary disease (COPD) with emphysema as their primary phenotype (COPD1 group), and patients with COPD with bronchitis as their primary phenotype (COPD2 group). RESULTS: Regarding the tidal volume curves of the three groups under various conditions, sixfold charts revealed that the tidal volume changed with the end-expiratory pressure fluctuations. In addition, regression coefficients for end-expiratory pressure fluctuations, (IPAP-EPAP) and (IPAP-EEPAP) exhibited a significant contribution to the tidal volume. The two coefficients in the normal, COPD1 and COPD2 groups were 52.294 and 10.414, 46.192 and -8.816, and 11.922 and 17.947, respectively. The circuit simulation results showed that the simulation curve fitted the experimental curve better by changing the coefficient of the descending edge of the expiratory phase. CONCLUSIONS: The study results suggest that the end-expiratory pressure fluctuation affects the body tidal volume. Compared with the bilevel positive airway pressure (PAP), the trilevel PAP provides additional respiratory support to the body during a respiratory difference in initial respiration and descent.

C-type lectin domain family 5, member A (CLEC5A, MDL-1) promotes brain glioblastoma tumorigenesis by regulating PI3K/Akt signalling.

OBJECTIVES: Glioblastoma is the most common malignant glioma of all brain tumours. It is difficult to treat because of its poor response to chemotherapy and radiotherapy and high recurrence rate after treatment. The aetiology of glioblastoma is a result of disorders of multiple factors. Depending on cell signal transduction, these glioblastoma-associated factors lead to cell proliferation, differentiation and apoptosis. Therefore, investigation of the potential factors which involved in the development of glioblastoma could provide a new target for the treatment of glioblastoma. MATERIALS AND METHODS: We analysed the transcript expression of CLEC5A in glioblastoma by accessing The Cancer Genome Atlas (TCGA). qRT-PCR was performed to detect the RNA expression of genes in cells and tissues, and Western blot was used to measure the protein levels (Cyclin D1, Bcl-2, BAX, PCNA, MMP2, MMP9, Akt and Akt phosphorylation) in tissues and cells. Cell proliferation, migration, invasion, cycle and apoptosis were measured by CCK-8, transwell and flow cytometry assays, respectively. Ki67 level and lung metastasis were determined by immunochemistry and H&E staining. RESULTS: In this study, we found that CLEC5A was highly upregulated in glioblastoma compared to normal brain tissues, which had an opposite relation with the overall patient survival. Downregulation of CLEC5A could inhibit cell proliferation, migration and invasion via promoting apoptosis and G1 arrest. In contrast, overexpression of CLEC5A stimulated cell proliferation, migration and invasion. In addition, we found that CLEC5A level was positively correlated with Akt phosphorylation level. Akt inhibitor or agonist could reverse the modulation effects of CLEC5A in glioblastoma. Moreover, In vivo results suggested that inhibition of CLEC5A significantly reduced tumour size, weight, cell proliferation ability and lung metastasis via inhibition of phosphorylation Akt. CONCLUSION: Both in vitro and in vivo evidences supported that CLEC5A was involved in glioblastoma pathogenesis via regulation of PI3K/Akt pathway. Thus, CLEC5A might serve as a potential therapeutic target in the treatment of glioblastoma in the future.

Pharmacokinetics and Bioequivalence Study of Hydroxychloroquine Sulfate Tablets in Chinese Healthy Volunteers by LC-MS/MS.

INTRODUCTION: Hydroxychloroquine (HCQ), 4-aminoquinoline, is an antimalarial drug and has become a basic therapy for rheumatic disease treatment. It can stabilize the condition of SLE patients and reduce the chances of patient relapse through its immunosuppressive function and antiinflammatory effects. This drug was absorbed completely and rapidly by oral administration, but has a prolonged half-life for elimination. The objective of this study was to evaluate the pharmacokinetic parameters and relative bioequivalence of a new generic (test) formulation with the branded (reference) formulation of HCQ in healthy Chinese male volunteers. This study was designed to acquire regulatory approval for the test formulation. METHODS: This study was conducted with a randomized, single-dose, two-period, and crossover design. The male subjects were randomly assigned to two groups at a 1:1 ratio to receive 0.2 g hydroxychloroquine sulfate tablets (0.1 g/piece) of the two formulations after a 3-month washout period then administered the alternate formulation. Study drugs were administered after overnight fasting (over 10 h). Plasma concentrations of hydroxychloroquine were measured by a validated LC-MS/MS method. The following pharmacokinetic properties were determined by a noncompartmental pharmacokinetic method: C max, T max, AUC0-t , AUC0-∝, and t 1/2. The bioequivalence between the test and reference products was assessed based on the following parameters: C max, AUC0-60d, and AUC0-∝ using the ANOVA method. If the 90% CI for AUC0-t was within 80-125% and for C max was within 70-143% of the statistical interval proposed by the SFDA, the two formulations were assumed bioequivalent. Concerning the main pharmacokinetic charateristics of hydroxychloroquine, a long half-life drug, the pharmacokinetic parameters of 0-72 h were determined according to the FDA. Furthermore, a comparison was made between the parameters at 0-60 days and 0-72 h to evaluate whether a truncated AUC method can be applied to estimate the relative bioavailability of HCQ. Tolerability was assessed by monitoring vital signs and laboratory tests and by questioning subjects about adverse events. RESULTS: The 90% CI of C max for HCQ is 103.8-142.3%; the AUC0-60 is 100-114.2% and AUC0-∝ 100-115.5%. Both met the criteria according to the SFDA's guidelines for bioequivalence. The relative bioavailability was 109.5% (according to AUC0-60d) and 110.7% (according to AUC0-∝). No serious or unexpected adverse events were observed. CONCLUSIONS: In this study, the pharmacokinetic studies and results were conducted so that the test and reference formulations of HCQ met the Chinese criteria for assuming bioequivalence. Both formulations were well tolerated in the population studies.

Inverse labeling-mass spectrometry for the rapid identification of differentially expressed protein markers/targets.

Comparative proteomic studies can lead to the identification of protein markers for disease diagnostics and protein targets for potential disease interventions. An inverse labeling strategy based on the principle of protein stable isotope labeling and mass spectrometric detection has been successfully applied to three general protein labeling methods. In contrast to the conventional single experiment approach, two labeling experiments are performed in which the initial labeling is reversed in the second experiment. Signals from differentially expressed proteins will distinguish themselves by exhibiting a characteristic pattern of isotope intensity profile reversal that will lead to the rapid identification of these proteins. Application of the inverse labeling method is demonstrated using model systems for protein chemical labeling, protein proteolytic labeling, and protein metabolic labeling. The methodology has clear advantages which are illustrated in the various studies. The inverse labeling strategy permits quick focus on signals from differentially expressed proteins (markers/targets) and eliminates ambiguities caused by the dynamic range of detection. In addition, the inverse labeling approach enables the unambiguous detection of covalent changes of proteins responding to a perturbation.

Inverse 15N-metabolic labeling/mass spectrometry for comparative proteomics and rapid identification of protein markers/targets.

The inverse labeling/mass spectrometry strategy has been applied to protein metabolic (15)N labeling for gel-free proteomics to achieve the rapid identification of protein markers/targets. Inverse labeling involves culturing both the perturbed (by disease or by a drug treatment) and control samples each in two separate pools of normal and (15)N-enriched culture media such that four pools are produced as opposed to two in a conventional labeling approach. The inverse labeling is then achieved by combining the normal (14)N-control with the (15)N-perturbed sample, and the (15)N-control with the (14)N-perturbed sample. Both mixtures are then proteolyzed and analyzed by mass spectrometry (coupled with on-line or off-line separation). Inverse labeling overcomes difficulties associated with protein metabolic labeling with regard to isotopic peak correlation and data interpretation in the single-experiment approach (due to the non-predictable/variable mass difference). When two data sets from inverse labeling are compared, proteins of differential expression are readily recognized by a characteristic inverse labeling pattern or apparent qualitative mass shifts between the two inverse labeling analyses. MS/MS fragmentation data provide further confirmation and are subsequently used to search protein databases for protein identification. The methodology has been applied successfully to two model systems in this study. Utilizing the inverse labeling strategy, one can use any mass spectrometer of standard unit resolution, and acquire only the minimum, essential data to achieve the rapid and unambiguous identification of differentially expressed protein markers/targets. The strategy permits quick focus on the signals of differentially expressed proteins. It eliminates the detection ambiguities caused by the dynamic range of detection. Finally, inverse labeling enables the detection of covalent changes of proteins responding to a perturbation that one might fail to distinguish with a conventional labeling experiment.