Investigation on the relationship between hemoglobin concentration and stroke risk: a bidirectional Mendelian randomization study.

Background: The relationship between hemoglobin concentration and stroke has garnered significant interest in the research community. However, findings from published observational epidemiological studies on this relationship have been inconclusive. By using publicly available genome-wide association study (GWAS) aggregated statistics, a two-sample Mendelian randomization analysis is conducted to explore the causal relationship between hemoglobin concentration and stroke. Methods: Summary statistics data from UK Biobank for hemoglobin concentration and from the FinnGen R9 and MEGASTROKE consortium for stroke are used. A series of quality control steps are taken to select eligible instrumental SNPs closely related to exposure. In order to make the conclusion more robust and reliable, several robust analysis methods are employed including inverse variance weighted, weighted median, MR-Egger regression, which are based on different assumptions of two-sample MR Analysis. Meanwhile, sensitivity analyses such as pleiotropy test and MR-Egg regression, are performed to mitigate horizontal pleiotropy and heterogeneity. Results: The two-sample Mendelian randomized study indicates a negative association between hemoglobin concentration and stroke, suggesting that hemoglobin concentration acts as a protective factor against stroke. From the FinnGen database, there is a negative association between hemoglobin concentration and stroke, with an odds ratio (OR) of 0.82 and a 95% confidence interval (CI) of 0.73-0.92, p = 0.0006. Similarly, the MEGASTROKE database findings reinforce this observation. The negative association between hemoglobin concentration and stroke (OR: 0.91, 95%CI: 0.83-1.00, p = 0.040), ischemic stroke (OR: 0.87, 95%CI: 0.79-0.96, p = 0.004), and cardiogenic stroke (OR: 0.82, 95% CI: 0.69-0.99, p = 0.039) further suggests that higher hemoglobin levels might confer a protective effect against these conditions. Conclusion: Hemoglobin concentration serves as a protective factor against stroke, and managing abnormal hemoglobin levels can effectively reduce the incidence of stroke.

Synthetic enhancers including TFREs improve transgene expression in CHO cells.

The human cytomegalovirus major immediate early gene (CMV) promoter is currently the most preferred promoter for recombinant therapeutic proteins (RTPs) production in CHO cells. To enhance the production of RTPs, five synthetic enhancers including multiple transcription factor regulatory elements (TFREs) were evaluated to enhance recombinant protein level in transient and stably transfected CHO cells. Compared with the control, four elements can enhance the report genes expression under both two transfected states. Further, the function of these four enhancers on human serum albumin (HSA) were investigated. We found that the transient expression can increase by up to 1.5 times, and the stably expression can maximum increase by up to 2.14 times. The enhancement of transgene expression was caused by the boost of their corresponding mRNA levels. Transcriptomics analysis was performed and found that transcriptional activation and cell cycle regulation genes were involved. In conclusion, optimization of enhancers in the CMV promoter could increase the production yield of transgene in transfected CHO cells, which has significance for developing high-yield CHO cell expression system.

MMP9 SNP and MMP SNP-SNP interactions increase the risk for ischemic stroke in the Han Hakka population.

OBJECTIVES: To investigate the association of eight variants of four matrix metalloproteinase (MMP) genes with ischemic stroke (IS) and whether interactions among these single nucleotide polymorphisms (SNPs) increases the risk of IS. METHODS: Among 547 patients with ischemic stroke and 350 controls, matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to examine eight variants arising from four different genes, including MMP-1 (rs1799750), MMP-2 (rs243865, rs2285053, rs2241145), MMP-9 (rs17576), and MMP-12 (rs660599, rs2276109, and rs652438). Gene-gene interactions were employed using generalized multifactor dimensionality reduction (GMDR) methods. RESULTS: The frequency of rs17576 was significantly higher in IS patients than in controls (p = .033). Logistic regression analysis revealed the AG and GG genotypes of rs17576 to be associated with a higher risk for IS, with the odds ratio and 95% confidence interval being 2.490 (1.251-4.959) and 2.494 (1.274-4.886), respectively. GMDR analysis showed a significant SNP-SNP interaction between rs17576 and rs660599 (the testing balanced accuracy was 53.70% and cross-validation consistency was 8/10, p = .0107). Logistic regression analysis showed the interaction between rs17576 and rs660599 to be an independent risk factor for IS with an odds ratio of 1.568 and a 95% confidence interval of 1.152-2.135. CONCLUSION: An MMP-9 rs17576 polymorphism is associated with increased IS risk in the Han Hakka population and interaction between MMP-9 rs17576 and MMP-12 rs660599 is associated with increased IS risk as well.

[Clinical effect of Liyan Tongqiao acupuncture in treatment of post-stroke dysphagia: an analysis based on diffusion tensor imaging].

OBJECTIVE: To investigate the clinical change of post-stroke dysphagia after the intervention of Liyan Tongqiao （relieving sore-throat and dredging orifices）acupuncture using cranial diffusion tensor imaging (DTI). METHODS: A total of 60 patients with post-stroke dysphagia were enrolled and randomly divided into Liyan Tongqiao acupuncture group and neurology treatment group, with 30 patients in each group. The patients in the neurology treatment group were given routine neurology treatment and swallowing rehabilitation training, and those in the Liyan Tongqiao acupuncture group received acupuncture at Sishencong (EX-HN1), Baihui (GV20), bilateral Tai-yang (EX-HN5), and bilateral Fengchi (GB20) and tongue triple acupuncture, with an electroacupuncture apparatus for EX-HN1, bilateral GB20, and tongue triple acupuncture, for a needle retaining time of 30 minutes each time, once a day and 5 times a week, in addition to the treatment in the neurology treatment group. Each course of treatment was 3 weeks, and both groups were treated for 2 courses. Swallowing function assessment and cranial DTI were performed after treatment. RESULTS: After 6 weeks of treatment, both groups had a marked improvement in swallowing function, a significantly greater change in video fluoroscopic swallowing study (VFSS) score and a higher mean FA value (P<0.05). Compared with the neurology treatment group, the Liyan Tongqiao acupuncture group had a marked improvement in swallowing function, a significantly greater change in VFSS score in the pharyngeal phase and a higher mean FA value (P<0.05). CONCLUSION: Liyan Tongqiao acupuncture can improve dysphagia and swallowing function in the pharyngeal phase in VFSS, possibly by promoting the remodeling of cerebral cortex and increasing the FA value of infarct zone through the stimulation of related acupoint signals.

Modeling and classification of gait patterns between anterior cruciate ligament deficient and intact knees based on phase space reconstruction, Euclidean distance and neural networks.

BACKGROUND: The anterior cruciate ligament (ACL) plays an important role in stabilizing translation and rotation of the tibia relative to the femur. ACL injury alters knee kinematics and usually links to the alternation of gait patterns. The aim of this study is to develop a new method to distinguish between gait patterns of patients with anterior cruciate ligament deficient (ACL-D) knees and healthy controls with ACL-intact (ACL-I) knees based on nonlinear features and neural networks. Therefore ACL injury will be automatically and objectively detected. METHODS: First knee rotation and translation parameters are extracted and phase space reconstruction (PSR) is employed. The properties associated with the gait system dynamics are preserved in the reconstructed phase space. For the purpose of classification of ACL-D and ACL-I knee gait patterns, three-dimensional (3D) PSR together with Euclidean distance computation has been used. These measured parameters show significant difference in gait dynamics between the two groups and have been utilized to form a feature set. Neural networks are then constructed to identify gait dynamics and are utilized as the classifier to distinguish between ACL-D and ACL-I knee gait patterns based on the difference of gait dynamics between the two groups. RESULTS: Experiments are carried out on a database containing 18 patients with ACL injury and 28 healthy controls to assess the effectiveness of the proposed method. By using the twofold and leave-one-subject-out cross-validation styles, the correct classification rates for ACL-D and ACL-I knees are reported to be 91.3[Formula: see text] and 95.65[Formula: see text], respectively. CONCLUSION: Compared with other state-of-the-art methods, the results demonstrate that gait alterations in the presence of ACL deficiency can be detected with superior performance. The proposed method is a potential candidate for the automatic and non-invasive classification between patients with ACL deficiency and healthy subjects.