Effect of thrombomodulin gene polymorphisms on venous thromboembolism: An analysis of evidence involving 6,629 patients.

BACKGROUD: The association between thrombomodulin gene (THBD) c.1418 C>T polymorphisms and the risk of venous thromboembolism (VTE) is controversial. The purpose of this meta-analysis was to evaluate THBD c.1418 C>T polymorphisms and the risk of VTE. METHODS: Computer searches were performed on the CNKI, Wanfang database, VIP database, PubMed, Embase, Web of Science, and Cochrane Library databases. The retrieval time limit was from the establishment of the database to June 2022. Case-control studies and cohort studies of THBD c.1418 C>T polymorphisms associated with VTE were included. The literature was screened according to inclusion and exclusion criteria, data extraction and literature quality evaluation. Meta-analysis was performed using STATA 14.0 software. RESULTS: A total of 12 literature were included, including 2980 cases in the case group and 3649 cases in the control group. The meta-analysis results showed no significant association of the THBD c.1418 C> T polymorphisms with the occurrence of VTE (T vs C: OR = 1.17, 95%CI = 0.93-1.48; TT vs CT+CC: OR = 1.00, 95%CI = 0.75-1.33; TT+CT vs CC: OR = 1.22, 95%CI = 0.94-1.59). Subgroup analyses revealed an increased risk of VTE in Asian populations due to THBD c.1418 C>T polymorphisms (T vs C: OR = 1.48, 95%CI = 1.06-2.07; TT vs CT+CC: OR = 1.80, 95%CI = 1.13-2.85; TT+CT vs CC: OR = 1.58, 95%CI = 1.07-2.32). THBD c.1418 C>T polymorphisms increased the risk of DVT (T vs C: OR = 1.51, 95%CI = 1.24-1.85; TT vs CT+CC: OR = 1.85, 95%CI = 1.10-3.12; TT+CT vs CC: OR = 1.64, 95%CI = 1.28-2.11). THBD c.1418 C>T polymorphisms reduced the risk of VTE in non-Asian populations (TT vs CT+CC: OR = 0.66, 95%CI = 0.45-0.98). CONCLUSION: THBD c.1418 C>T polymorphisms is associated with VTE in Asian population, which may be a factor in the occurrence of VTE in Asian population. THBD c.1418 C>T polymorphisms increases the risk of DVT. Given the limitations of this meta-analysis, the conclusions require being further supported by large-scale and high-quality studies.

Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese population with colorectal cancer.

BACKGROUND: Molecular characteristics of CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been well documented in Western, but not in Chinese, populations. METHODS: We investigated the incidence of CIMP, BRAF/KRAS mutation, and microsatellite instability (MSI) in a Chinese population with CRC (n = 401) and analysed associations between CIMP status and clinicopathological and molecular features. RESULTS: A total of 41 cases, 310 cases, and 40 cases were classified as CIMP-high, CIMP-low, and CIMP-negative, respectively. We detected a significantly low incidence of BRAF mutation in adenomas (2%) and CRC (0.7%), and a relatively low incidence of KRAS mutation (24.9%) compared with that in other populations. We also detected a relatively low incidence of CIMP-high (10.2%), which was significantly associated with younger age (≤49 years of age), female sex, and proximal tumour location. CONCLUSIONS: This study revealed unique characteristics of CIMP in a Chinese population with colorectal cancer. Developing specific CIMP markers based on unique populations or ethnic groups will further help to fully elucidate CIMP pathogenesis.

[Study on an Exoskeleton Hand Function Training Device].

Based on the structure and motion bionic principle of the normal adult fingers, biological characteristics of human hands were analyzed, and a wearable exoskeleton hand function training device for the rehabilitation of stroke patients or patients with hand trauma was designed. This device includes the exoskeleton mechanical structure and the electromyography (EMG) control system. With adjustable mechanism, the device was capable to fit different finger lengths, and by capturing the EMG of the users' contralateral limb, the motion state of the exoskeleton hand was controlled. Then driven by the device, the user's fingers conducting adduction/abduction rehabilitation training was carried out. Finally, the mechanical properties and training effect of the exoskeleton hand were verified through mechanism simulation and the experiments on the experimental prototype of the wearable exoskeleton hand function training device.

[Kinematics Modeling and Analysis of Central-driven Robot for Upper Limb Rehabilitation after Stroke].

The present paper proposed a central-driven structure of upper limb rehabilitation robot in order to reduce the volume of the robotic arm in the structure, and also to reduce the influence of motor noise, radiation and other adverse factors on upper limb dysfunction patient. The forward and inverse kinematics equations have been obtained with using the Denavit-Hartenberg (D-H) parameter method. The motion simulation has been done to obtain the angle-time curve of each joint and the position-time curve of handle under setting rehabilitation path by using Solid Works software. Experimental results showed that the rationality with the central-driven structure design had been verified by the fact that the handle could move under setting rehabilitation path. The effectiveness of kinematics equations had been proved, and the error was less than 3° by comparing the angle-time curves obtained from calculation with those from motion simulation.

[Research on proportional control system of prosthetic hand based on FMG signals].

The control of prosthetic hand is always a focus in prosthesis research. For solving current problems of controlling signals of skin surface electrical signals, we applied force myography (FMG) signals in prosthetic control of this system. The control system based on FMG signals were designed, containing signal acquisition and pre-processing, prosthetic control, motor driving and so on. Two-freedom artificial hand with proportional control was proposed through acquiring two-channel FMG signals from the amputee stump. The proportional control of prosthetic hand was achieved according to the average of FMG amplitude. The results showed that the control system had a great potential to control artificial hand and to realize speed adjustment effectively. Besides, the Virtual instrument software LabVIEW is adopted to establish the FMG signal collection and calibration of experiment system.

Risk factors for post-traumatic stress disorder in acute trauma patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most commonly reported mental health consequences, followed by disasters and traumatic events, either natural or man-made. At present, there are no unified results for the prevalence rate of PTSD in patients suffering from acute trauma and related influencing factors. Therefore, the purpose of this study is to systematically evaluate the existing literatures, thus obtaining a comprehensive estimation of the combined prevalence rate of PTSD and related factors in trauma patients, so as to provide evidence support for clinical disease prediction models and intervention strategies. METHODS: Published articles will be retrieved from PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Database, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Database. Research reports will be searched in March 2021. STATA 14.0 software will be applied for data analysis. Mantel-Haenszel fixed effect model or DerSimonian-Laird random effect model will be selected to estimate the pooled prevalence of PTSD in patients with acute trauma and associated factors. RESULTS: We will disseminate the findings of this systematic review and meta-analysis via publications in peer-reviewed journals. CONCLUSIONS: The results of this analysis can be used to establish a risk prediction model of PTSD in patients experiencing acute trauma, so as to provide intervention strategies. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/Z275U.

[Detection of multiple gene mutations in non-small-cell lung cancer by suspension microarray].

OBJECTIVE: To construct a high-throughput suspension microarray for detecting the hotspot gene mutations of p53, p16, retinoblastoma (Rb) and epidermal growth factor receptor (EGFR) and to investigate the significance of this multimarker panel in molecular diagnosis of non-small-cell lung cancer (NSCLC). METHODS: The specific probes of normal or mutated sequences targeting the hotspot mutation sites of p53, p16, Rb and EGFR were designed and immobilized to carboxylated Luminex microspheres (micro-beads). Genomic DNA was extracted from 65 specimens of cancer tissues and 20 adjacent normal lung tissues. p53, p16, Rb and EGFR genes were amplified by PCR, hybridized with the specific probes on the beads and measured using Luminex 100. RESULTS: The single gene mutations of p53, p16, Rb or EGFR in NSCLC specimens were 53.8% (35/65), 20.0% (13/65), 7.7% (5/65) or 35.4% (23/65) respectively. The para-tumor normal tissue specimens were 5.0% (1/20), 5.0%(1/20), 0 and 0 respectively. For combined detections of four genes, the sensitivity, specificity and accuracy were 81.5% (53/65), 90.0% (18/20) and 83.5%(71/85) respectively. The mutation rates of this panel in stage I, stage II and stage III were 78.3% (18/23), 80.0% (16/20) and 86.4% (19/22) respectively. CONCLUSIONS: A high-throughput suspension microarray with a higher specificity and sensitivity has been built. It may be used to simultaneously detect the gene mutations of p53, p16, Rb or EGFR in NSCLC specimens. This suspension microarray is helpful to improve the sensitivity of molecular diagnosis of NSCLC and guide the molecular targeting therapy of NSCLC.

Identification and validation of colorectal neoplasia-specific methylation biomarkers based on CTCF-binding sites.

To date, the sensitivity of currently available biomarkers based on the methylation of gene promoters is suboptimal for detecting adenomas and early-stage colorectal cancer (CRC). We aimed to develop biomarkers with methylated DNA binding sites of the multifunctional transcriptional factor CTCF for early detection of CRC. Using combined analyses of genome-wide occupation and the methylation profile of CTCF-binding sites, we identified candidate CTCF-binding sites. Then, we applied methylation-sensitive high-resolution melting (MS-HRM) and mass spectrometry analysis to screen and validate these candidate sites in diverse sample sets. We identified a set of colorectal neoplasia-specific biomarkers with robust performance. The top five biomarkers were selected and recommended for early detection of colorectal neoplasia. All of the five novel biomarkers exhibited a more robust discriminatory performance than that by BMP3 and NDRG4, two currently acknowledged robust methylation biomarkers. When the five new biomarkers were considered as a marker panel and tumor-positive was defined as having two or more (of the five) positive biomarkers, the marker panel could achieve a sensitivity of 91.67% for adenomas, 97.44% for Stage I CRC, 94.06% for Stage II CRC, 93.62% for Stage III CRC, and 93.54% for total colorectal tumors with a specificity of 94.05%. To our knowledge, this is the first study for colorectal neoplasia-specific methylation biomarkers based on CTCF-binding sites. Using a similar strategy, CTCF-binding sites could be potentially developed into biomarkers for other tumors. In summary, this study opens a new area in developing biomarkers for tumor prevention and treatment.

[Refolding of the fusion protein of recombinant enterokinase light chain rEKL].

The fusion protein of enterokinase light chain, DsbA-rEKL, was expressed mainly in inclusion body in E. coli. The recombinant bacteria was fermented to high density, with high expression of the fusion protein. After being washed with 0.5% Triton X-100 and 4mol/L urea, the inclusion body was dissolved in 6mol/L guanidine and 100mmol/L DTP, derivatized by cystine and refolded by pulse refolding. The strategy of pulse refolding involved the addition of 0.03mg/mL of fusion protein until its final concentration reached 0.3mg/mL. The refolded protein was autocleaved and the active EKL molecule was released after adding 2mmol/L CaCl2. Using the two-step purification processes of IDA-Sepharose chromatography and Q-Sepharose chromatography, the purity of rEKL was found to be above 95%, with a high activity to cleave the recombinant reteplase fusion protein Trx-rPA. The yield of purified rEKL was more than 60mg/L of cultures. As a result, the therapeutic proteins like rPA could be produced on a large-scale in a way such as expressed in the form of fusion proteins.