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This study aimed to explore the effects of fatigue on the balance and ankle proprioception during drop landing of individuals with chronic ankle instability (CAI). A total of 35 participants with unilateral CAI and 35 healthy participants participated in this study. A static balance test, dynamic balance test, and ankle proprioception test were conducted before and after fatigue. Fatigue was induced with turn back runs and vertical jumps protocol. Sway distance of the center of pressure (COP), root mean square of the COP (RMS), total excursions (TOTEX), mean velocity (MVELO), 95% confidence ellipse area of the COP movements (95% AREA), Normalise Reach Distance in the anterior (ANT), posteromedial (PM), and posterolateral (PL) directions, and the area under the curve (AUC) were calculated and analyzed. There were significant group by fatigue interactions for static balance variables, normalise reach distance in the PM and PL directions, and AUC. Fatigue reduced balance and ankle proprioception in individuals with CAI. After fatigue, static and dynamic balance and ankle proprioception during drop landing were significantly worse in the CAI group than in the control group. Fatigue had a significant negative effect on balance and ankle proprioception in CAI patients. Therefore, fatigue may be an important factor causing repeated ankle sprain in CAI patients.

Background Programmed cell death protein 1 (PD-1), as an immune checkpoint cell membrane receptor, negatively regulates T cell activation via its immune receptor, the tyrosine-based switch motif (ITSM). The purpose of this research was to evaluate the antitumor activity T cells with the ITSM mutation of PD-1 on non-small cell lung cancer (NSCLC) in vitro and in vivo. Methods In this study, the tyrosine of ITSM in cytotoxic T cells was mutated using the adenine base editor (ABE)-xCas9 system to evaluate its effect on the antitumor activity of T cells against NSCLC. Results Results showed that the PD-1-deficient T cells enhanced the death of the cocultured NSCLC cells compared with the normal T cells and saline solution. PD-1-deficient T cells also changed the interleukin 2(IL-2), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion of T cells compared with those of the normal T cells. The effectiveness of ITSM mutation in enhancing the antitumor activity of PD-1-deficient T cells was verified in vivo by using a mouse xenograft model. The xenografted mice treated with PD-1-deficient T cells demonstrated repressed tumor growth of the NSCLC cells compared with those treated with normal T cells and saline solution. Conclusions The mutation of ITSM in cytotoxic T cell via the ABE-xCas9 system can significantly enhance the antitumor activity of T cells.

MicroRNA-92a (miR-92a) is an evolutionarily conserved noncoding small RNA that can regulate gene expression after transcription. Previous studies have found that miR-92a is overexpressed in many tumors and can regulate numerous tumor suppressor genes negatively, with relevant effects on the development of different tumors, by regulating the DUSP10/c-Jun N-terminal kinase (JNK), phosphatase and tensin homologs (PTEN)/AKT, Wnt and EP4/Notch1 signaling axes. MiR-92a also promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) through the Rho-associated coiled-coil-forming kinase/myosin light chain kinase signaling pathway and inhibits VSMC apoptosis through the MKK4/JNK signaling pathway. Moreover, miR-92a affects endothelial functions; mediates endothelial dysfunction in chronic kidney diseases; mediates THBS1 inhibition; promotes the migration, proliferation and angiogenesis of neighboring endothelial cells (ECs); mediates the Nrf2/KEAP1/ARE signaling pathway to regulate vascular endothelial aging; and is involved in immune responses to activate ECs. This review summarizes the potential role and pathogenic mechanism of the miR-92a gene in certain diseases to provide possible new treatment options.

Background Ankle instability limits physical activities and undermines a person’s quality of life. Tai Chi’s health benefits have been reported in different population groups. However, the effects of Tai Chi on neuromuscular function among young adults with functional ankle instability (FAI) remain unclear. Therefore, we aim to investigate the effect of Tai Chi on young adults with FAI. Methods This study will be conducted as a randomized controlled trial with blinded assessors. A total of 104 young adults with FAI will be recruited and randomly assigned to intervention and control groups. The participants in the simplified Tai Chi exercise program (STCEP) group will receive a 12-week Tai Chi training. The participants in the control group will receive a low-intensity exercise program and health education for 12 weeks. The primary and secondary outcomes will be assessed at baseline, 4th, 8th, and 12th weeks. Primary outcome measures will include the Cumberland Ankle Instability Tool (CAIT) score, kinematics/kinetics data, electromyography during single-leg landing tasks, and the modified Star Excursion Balance Test (mSEBT). Secondary outcome measures will include the total time of Dynamic Leap and Balance Test (DLBT), ankle muscle strength, and ankle proprioception. Discussion This study will investigate the effects of Tai Chi exercise on the neuromuscular function of patients with FAI, as indicated by ankle joint biomechanics, ankle proprioception, balance, ankle muscle strength, and ankle muscle activation. Results will demonstrate that Tai Chi can be an effective exercise for young adults with FAI. Trial registration Chinese Clinical Trial Registry ChiCTR2100044089. Registered on 10 March 2021

Rationale: With the spread of computers and mobile phones, cervical spondylosis has become a common occupational disease in clinics, which seriously affects the quality of life of patients. We used a nonsurgical spinal decompression system (SDS) combined with physical therapy electroacupuncture (EA) to treat a case of mixed cervical spondylosis caused by multi-level cervical disc herniation, and we achieved satisfactory results. Patient concerns: A 44-year-old Caucasian Asian woman presented with neck pain and numbness on the left side of the limb. MRI showed the patient's C3–C7 segment cervical disc herniation, and the flexion arch of the cervical spine was reversed. Diagnosis: The patient was diagnosed with a mixed cervical spondylosis. Interventions: The patient received a month of physical therapy (SDS traction combined with EA). Outcomes: Before and after treatment: VAS score of neck pain decreased from 8 to 0; Cervical spine mobility returned to normal; The grip strength of left hand increased from 7.5 kg to 19.2 kg; Cervical curvature index changed from −16.04% to −3.50%; the physiological curvature of the cervical spine was significantly restored. There was no dizziness or neck discomfort at 6 month and 1 year follow-up. Lessons subsetions: SDS traction combined with EA is effective for the treatment of cervical disc herniation and can help restore and rebuild the biomechanical balance of the cervical spine.

Great efforts have been made on the algorithms that deal with RNA-seq data to enhance the accuracy and efficiency of differential expression (DE) analysis. However, no consensus has been reached on the proper threshold values of fold change and adjusted p-value for filtering differentially expressed genes (DEGs). It is generally believed that the more stringent the filtering threshold, the more reliable the result of a DE analysis. Nevertheless, by analyzing the impact of both adjusted p-value and fold change thresholds on DE analyses, with RNA-seq data obtained for three different cancer types from the Cancer Genome Atlas (TCGA) database, we found that, for a given sample size, the reproducibility of DE results became poorer when more stringent thresholds were applied. No matter which threshold level was applied, the overlap rates of DEGs were generally lower for small sample sizes than for large sample sizes. The raw read count analysis demonstrated that the transcript expression of the same gene in different samples, whether in tumor groups or in normal groups, showed high variations, which resulted in a drastic fluctuation in fold change values and adjustedp-values when different sets of samples were used. Overall, more stringent thresholds did not yield more reliable DEGs due to high variations in transcript expression; the reliability of DEGs obtained with small sample sizes was more susceptible to these variations. Therefore, less stringent thresholds are recommended for screening DEGs. Moreover, large sample sizes should be considered in RNA-seq experimental designs to reduce the interfering effect of variations in transcript expression on DEG identification.

Background RNA sequencing (RNA-Seq) has been widely applied in oncology for monitoring transcriptome changes. However, the emerging problem that high variation of gene expression levels caused by tumor heterogeneity may affect the reproducibility of differential expression (DE) results has rarely been studied. Here, we investigated the reproducibility of DE results for any given number of biological replicates between 3 and 24 and explored why a great many differentially expressed genes (DEGs) were not reproducible. Results Our findings demonstrate that poor reproducibility of DE results exists not only for small sample sizes, but also for relatively large sample sizes. Quite a few of the DEGs detected are specific to the samples in use, rather than genuinely differentially expressed under different conditions. Poor reproducibility of DE results is mainly caused by high variation of gene expression levels for the same gene in different samples. Even though biological variation may account for much of the high variation of gene expression levels, the effect of outlier count data also needs to be treated seriously, as outlier data severely interfere with DE analysis. Conclusions High heterogeneity exists not only in tumor tissue samples of each cancer type studied, but also in normal samples. High heterogeneity leads to poor reproducibility of DEGs, undermining generalization of differential expression results. Therefore, it is necessary to use large sample sizes (at least 10 if possible) in RNA-Seq experimental designs to reduce the impact of biological variability and DE results should be interpreted cautiously unless soundly validated.

Additional file 4: Supplementary Figure S2. Dispersion of normalized read counts for the 10 non-common genes in LUAD. Mild outliers (more than 1.5 IQR’s from the box, indicated by O) and extreme outliers (more than 3 IQR’s from the box, indicated by *) are shown. The number beside the marker shows the normalized count value of the point. RII and RIII refer to repeat II and repeat III, respectively. Capital letters “T” and “N” represent the tumor group and the normal group, respectively. IQR indicates the interquartile range.

Additional file 3: Supplementary Figure S1. Dispersion of normalized read counts for the 10 non-common genes in KIRC. Mild outliers (more than 1.5 IQR’s from the box, indicated by O) and extreme outliers (more than 3 IQR’s from the box, indicated by *) are shown. The number beside the marker shows the normalized count value of the point. RII and RIII refer to repeat II and repeat III, respectively. Capital letters “T” and “N” represent the tumor group and the normal group, respectively. IQR indicates the interquartile range.

Additional file 5: Supplementary Figure S3. Diagram of experimental design for the BRCA dataset. The processes of sampling and analysis for the KIRC and LUAD datasets were the same as that of BRCA. The numbers of tumor tissue samples and adjacent normal tissue samples for KIRC were 526 and 72, respectively, while the two numbers were 509 and 58, respectively, for LUAD. Restrained by the number of normal tissue samples which was far less than the number of tumor samples for each cancer type, the maximum number of biological replicates for BRCA, KIRC, and LUAD was accordingly set at 24, 18, and 14, respectively.

Additional file 1: Supplementary Table S1. Detailed %CV, Log2FC, and FDR values for the 10 non-common DEGs in KIRC

The aim of the present study was to investigate the role of miR-92a in lipid metabolism in hypoxic rats. Microarray analysis and reverse transcription-quantitative (RT-q)PCR were used to detect changes in the mRNA expression levels of miR-92a in the epididymal fat of hypoxic and normoxic rats. The downstream target mRNA of miR-92a was predicted using bioinformatics analysis and verified using a dual luciferase reporter assay. Changes in the expression of frizzled (Fzd)10 and c-Myc in the epididymal fat were detected using RT-qPCR and western blotting. Microarray analysis and RT-qPCR results showed that the expression of miR-92a was significantly lower in the fat tissues of the hypoxic rats compared with the normoxic rats. The results of the dual luciferase reporter assay showed that the target gene of miR-92a was Fzd10, which is an acceptor in the Wnt pathway. Fzd10 expression was upregulated in the hypoxic rats. The mRNA expression levels of c-Myc, which is located downstream of the Wnt pathway, was increased significantly. The increase in the mRNA and protein expression levels of Fzd10 and c-Myc may be associated with miR-92a downregulation. Downregulation of miR-92a in-turn may result in lipolysis through the regulation of the Wnt/β-catenin signaling pathway, and thus weight loss in the rats.

Melamine is a raw material in the chemical industry. Because of its high nitrogen content, melamine has been utilized by unscrupulous businessmen as a food additive to enhance the indices of protein content in food and feed testing. Tetrahymena has long been used as an excellent model organism in toxicological studies. The purpose of the present study was to determine the effect of melamine on Tetrahymena. In the present study, the effects of melamine on the proliferation and mating rate of Tetrahymena were examined by microscopic counting of the cell numbers. The comet assay and DAPI nuclear staining were performed to analyze the changes in the Tetrahymena genome. Flow cytometric analysis was conducted to detect apoptosis. Furthermore, RT-PCR was performed to determine the changes in the expression of the metallothionein gene in Tetrahymena that underwent stress treatment with varying concentrations of melamine. The results indicated that melamine affected the proliferation and sexual reproduction of Tetrahymena. High melamine concentrations damaged the Tetrahymena genome to a certain extent and induced apoptosis in the organism. Expression of the metallothionein gene was upregulated in Tetrahymena exposed to melamine stress to ameliorate melamine-induced damage. These results indicated that melamine displayed significant toxicity to Tetrahymena cells.

Cordycepin, a 3-deoxyadenosine, is the predominant functional component of the fungus Cordyceps militaris, a traditional Chinese medicine. Previous studies investigating the inhibition of cancer cells by cordycepin identified that it not only promotes cell apoptosis, but also controls cell proliferation. Furthermore, studies have elucidated the molecular mechanisms of inhibiting cell proliferation by cordycepin binding the A3 adenosine receptor, activating G protein, inhibiting cAMP formation, decreasing glycogen synthase kinase-3β/β-catenin activation and suppressing cyclin D1 and c-myc expression. The most significant signaling pathway in which cell apoptosis is induced by cordycepin is the caspase pathway. Cordycepin induces cell apoptosis via binding the DR3 receptor and consequently activating caspase-8/-3. Taken together, these studies demonstrate that cordycepin may be used as a natural medicine, as it can not only control tumor cell proliferation, but also induce cancer cell apoptosis.

BACKGROUND Several studies have focused on the association between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism; however, the results are conflicting. The effects of statins show significant variability between individuals. This meta-analysis aimed to investigate the effects of the SLCO1B1 c.521T>C polymorphism on the lipid-lowering effects of statins. METHODS We systematically searched PubMed and Web of Science to screen relevant studies. Meta-analysis was performed to identify the association between SLCO1B1 c.521 polymorphisms and the lipid-lowering effects of statins on the basis of the standard mean difference (SMD) and 95% confidence intervals (CIs). Additionally, we checked for heterogeneity (I(2)) among studies and evidence of publication bias. We obtained eight studies including 2,012 wild genotype (T/T) and 526 variant genotype (T/C and C/C) cases. RESULTS No significant difference was observed in the lipid-lowering efficacy of statins between the wild and variant genotypes of SLCO1B1, with a pooled SMD of 0.03 (95% CI: -0.07-0.13). Furthermore, there was no significant effect in the meta-analyses of the variant heterozygote, homozygote, and Chinese populations. Subgroup meta-analysis indicated that the time required for the statin to take effect did not significantly affect the association between lipid-lowering efficacy of statins and SLCO1B1 c.521T>C polymorphism. However, the wild genotype improved the lipid-lowering efficacy of simvastatin with a pooled SMD of -0.26 (95% CI: -0.47- -0.05). CONCLUSIONS No significant association was detected between the lipid-lowering efficacy of statins and the SLCO1B1 c.521T>C polymorphism, with the exception of simvastatin.

The elderly are prone to stair descent falls under low illumination. Tai Chi, a traditional Chinese conditioning exercise, has been proved to improve body stability by altering body condition, gait, and proprioception. This study investigates whether Tai Chi exercise could improve body stability during stair descent under high and low illumination. Three groups of elderly women who practice Tai Chi, brisk walking, and no exercise were included. They descended from a simulated staircase. Tai Chi participants decreased horizontal velocity, centre of mass (COM) sway, and increased foot clearance compared with other participants, these movements could increase body stability; Compared with under high illumination, Tai Chi participants decreased horizontal velocity, loading rate, braking impulse, and increased inclination angle, COM sway, centre of pressure displacement under low illumination. Tai Chi participants were more sensitive to the difference in illumination, and took corresponding strategies to stabilize their bodies during stair descent.

Soy isoflavones are compounds found in soybean and soybean products. They have been reported to possess numerous physiological properties, such as antitumor, anti-menopausal (female) osteoporosis and anti-aging. They have also been reported to improve learning and memory skills in menopausal women and aid in the prevention and treatment of heart disease, diabetes and Kawasaki disease (KD). In this review, the effects of soy isoflavones on various diseases were analyzed. Based on the analysis, it was hypothesized that the function of soybean isoflavones in the prevention and treatment of various diseases results from their phytoestrogen and antioxidant properties. However, due to their phytoestrogen properties, it is recommended that the risks of soy isoflavone intake as food and/or medical treatment be further evaluated.

Background: High-mobility group A1 (HMGA1) polymorphism has been suspected as a gene variant associated with type 2 diabetes (T2D). However, conflicting outcomes have been reported. Objective: This meta-analysis aimed to predict the association between the HMGA1 variant IVS5-13insC and T2D. Methods: Statistical analyses were performed using Stata/SE 12.0 software. Results: A total of 11 case-control studies in 6 articles were included. Results suggested that the HMGA1 variant IVS5-13insC was associated with an increased risk of insulin resistance (OR = 0.61, 95% CI 0.56 to 0.66, P < 0.0001), T2D (OR = 0.67, 95% CI 0.61 to 0.73, P < 0.0001), particularly for Caucasians with increased risks of T2D (OR = 0.56, 95% CI 0.49 to 0.65, P < 0.0001) compared with wild-type subjects. Conclusion: This meta-analysis indicated that the HMGA1 variant IVS5-13insC can be a risk factor of T2D development, particularly among Caucasians. Significant risks were also found (Asian: OR = 0.74, 95% CI: 0.63 to 0.86, P < 0.0001, Hispanic-American: OR = 0.81, 95% CI: 0.65 to 1.01, P < 0.0001) in non-Caucasian population. However, ethnical studies should be conducted to reveal whether the HMGA1 variant IVS5-13insC is associated with an increased risk of T2D. Keywords: HMGA1, type 2 diabetes, insulin resistance, variant, meta-analysis.