N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via ß-catenin/MYC/LDHA axis mediated glycolytic reprogramming.

Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via ß-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/ß-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/ß-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.

Performance of 2D-shear wave elastography in autoimmune hepatitis-primary biliary cholangitis overlap syndrome.

PURPOSE: To evaluate the diagnostic values of liver stiffness (LS) measured by 2D-SWE, fibrosis index based on the four factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and GGT to PLT ratio (GPR) for assessing liver fibrosis and high-risk esophageal varices (EVs) in patients with autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome. METHODS: Data of 141 patients were retrospectively collected. Liver fibrosis was staged according to the Scheuer scoring system. The Spearman correlation coefficient was used for correlation analysis. Receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic performance. RESULTS: LS and FIB-4 were positively correlated with the fibrosis stage (r = 0.555 and 0.198, respectively). LS had significantly higher areas under the ROC curves (AUROCs) values than FIB-4 for predicting advanced fibrosis (0.818 vs. 0.567, P < 0.001), cirrhosis (0.879 vs. 0.637, P < 0.001), whereas LS and FIB-4 similarly predicted significant fibrosis (0.748 vs. 0.638, P = 0.071) and high-risk EVs (0.731 vs. 0.659, P = 0.303). The optimal cut-off values of 2D-SWE for detecting significant fibrosis, advanced fibrosis, cirrhosis, and high-risk EVs were 8.7 kPa, 12.8 kPa, 14.0 kPa, and 11.0 kPa, respectively. LS values were influenced by fibrosis stage, serum GGT, albumin, and total bilirubin levels. The overall concordance rate of the liver stiffness vs. Scheuer stages was 49.65%. CONCLUSIONS: 2D-SWE shows significantly greater diagnostic accuracy than serum fibrosis indexes for diagnosing advanced fibrosis and cirrhosis in patients with AIH-PBC overlap syndrome.

The miR-133b/brefeldin A-inhibited guanine nucleotide-exchange protein 1 (ARFGEF1) axis represses proliferation, invasion, and migration in cervical cancer cells.

Cervical cancer is a common gynecological malignancy, and miR-133b is an abnormally expressed cervical cancer gene, which suggests that miR-133b may be involved in the occurrence and development of cervical cancer. However, the underlying mechanism is still unclear. miR-133b was overexpressed or silenced in the cervical cancer cell line C33A. Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (ARFGEF1) was combined with overexpression of miR-133b in C33A cells. Cell Counting Kit-8, clone formation, and Transwell assays were performed to determine the influence of miR-133b and ARFGEF1 on clone formation, proliferation, migration, and invasion of C33A cells. The interaction between miR-133b and ARFGEF1 was verified using a luciferase reporter assay. Finally, the mRNA and protein expression of miR-133b and ARFGEF1 in the tumor and adjacent normal tissues of cervical cancer patients was detected by real-time quantitative PCR, Western blotting, and immunohistochemistry. The results indicated that miR-133b up-regulation suppressed the proliferation, invasion, migration, and clone formation abilities of C33A cells (P < 0.05). However, silence of miR-133b promoted the proliferation, invasion, and migration of C33A cells (P < 0.05). Clone formation ability of C33A cells was also elevated by miR-133b deficiency (P < 0.05). Moreover, miR-133b interacted with ARFGEF1 and repressed ARFGEF1 expression in C33A cells (P < 0.05). ARFGEF1 overexpression weakened miR-133b overexpression-mediated inhibition of proliferation, invasion, and migration of C33A cells (P < 0.05). miR-133b expression was decreased, and ARFGEF1 was up-regulated in tumor tissues of cervical cancer patients (P < 0.05). All results revealed that miR-133b suppresses cervical cancer progression by inhibiting proliferation, invasion, and migration of cervical cancer cells via targeting ARFGEF1. Thus, our study determined the mechanism of miR-133b in cervical cancer, and confirmed miR-133b/ARFGEF1 may become a potential therapeutic target for cervical cancer.

N klA Case Report on a IV-degree Thermal Crush Injury of Right Upper Arm: The Application of Functional Prosthesis Implantation Technology.

Severe IV-degree thermal crush injury of limbs involved the subcutaneous fascia, muscle and bone, which may lead to amputation and has a great impact on the patient's quality of life. We can repair wounds with pedicle flaps or even free flaps, However, there are still huge challenges in bone defect of extremities and functional reconstruction. In recent years, with the development of functional prostheses, we have reconstructed limb functions in many patients helping them to complete their daily lives. We report a case where the right upper arm was injured by thermal crush, leading severe burns to the skin, fascia, muscle and bone. We applied a pedicled latissimus dorsi flap and a free anterolateral thigh flap to repair the wound, and realized the function of limb salvage and movement of the right upper arm by implanting 3D printed scapula, upper arm, and elbow joint prostheses. This case illustrates that IV-degree burns involving bones have new technologies to repair and achieve mobility now.

Combination of ablative fractional carbon dioxide laser and platelet-rich plasma treatment to improve hypertrophic scars: a retrospective clinical observational study.

BACKGROUND: Hypertrophic scars are one of the main complications that affect the quality of life of patients after burns. Many methods have been shown to be effective in the treatment of hypertrophic scars, such as ablative fractional CO2 laser (AFCL) and platelet-rich plasma (PRP). However, there are few studies on the effect of the combined application of these measures. The purpose of this study was to explore the therapeutic effect of AFCL combined with PRP on hypertrophic burn scars. METHODS: A retrospective clinical observation study was conducted on 50 patients with hypertrophic burn scars. The AFCL+PRP group included 31 patients who received AFCL combined with PRP treatment; the AFCL group included 19 patients who received AFCL treatment only. The University of North Carolina 4P Scar Scale (UNC4P) and the Vancouver Scar Scale (VSS) scores that were collected before each treatment were used as indicators of the effectiveness of the previous treatment. The scores recorded at the second, fourth and seventh months were analysed. RESULTS: The demographic data of the 2 groups were not significantly different. Before treatment, there was no difference in the UNC4P and VSS scores between the 2 groups. There was a significant decline in the UNC4P and VSS total scores over 6 months in both groups (p < 0.05) and scores in the 2 groups were comparable after 3 and 6 months (p < 0.05). UNC4P scores in the AFCL+PRP group decreased from a mean of 8.26 to 2.61 (p < 0.05) with a concomitant drop in VSS scores from a mean of 11.74 to 6.06 (p < 0.01). In the AFCL group UNC4P and VSS scores decreased from 7.68 to 4.63 (p < 0.05) and from 10.89 to 8.16 (p < 0.05), respectively. The sub-items of these 2 assessments were analysed and the results suggest that AFCL combined with PRP can comprehensively improve scarring. CONCLUSIONS: This study shows that PRP is an effective adjunct for AFCL in the treatment of hypertrophic burn scars and that the combination of PRP and AFCL proved to be more useful than AFCL alone. This combination may be a new and effective clinical practice for the treatment of scars. However, larger and higher-level clinical studies are still needed to determine its efficacy and possible mechanisms.

Effects of different returning method combined with decomposer on decomposition of organic components of straw and soil fertility.

In view of the problems of low straw decomposition rates and reduced soil fertility in southern Liaoning, China, we investigated the effects of no-tillage mode (NT), deep loosening + deep rotary tillage mode (PT), rotary tillage mode (RT) and the addition of decomposing agent (the next is called a decomposer) (NT + S, PT + S, RT + S) on the decomposition proportion of straw, respectively, by using the nylon net bag method in combination with 365-day field plot experiments. The decomposition rules of cellulose, hemicellulose and lignin as well as the dynamics of soil organic carbon (SOC), soil microbial biomass carbon (MBC) and soil dissolved organic carbon (DOC) in straw returned to the field for 15, 35, 55, 75, 95, 145 and 365 days were analyzed. The results showed that in the short term, the decomposition of straw was better in both the rotray tillage and deep loosening + deep rotary modes than in the no-tillage mode, and the addition of decomposer significantly promoted the decomposition of straw and the release of carbon from straw, among them, the RT + S treatment had the highest straw decomposition proportion and carbon release proportion in all sampling periods. After a one year experimental cycle, the RT + S treatment showed the highest proportion of cellulose, hemicellulose and lignin decomposition with 35.49%, 84.23% and 85.50%, respectively, and soil SOC, MBC and DOC contents were also higher than the other treatments with an increase of 2.30 g kg-1, 14.22 mg kg-1 and 25.10 mg kg-1, respectively, compared to the pre-experimental soil. Our results show that in the short term, to accelerate the decomposition rate of returned straw and increase the content of various forms of carbon in soil, rotary tillage can be used to return the straw to the field, while also spraying straw decomposer on its surface. This experiment used a new straw decomposer rich in a variety of microorganisms, combined with the comparison of a variety of straw return modes, and in-depth study of straw decomposition effects of cellulose, hemicellulose and lignin. Thus, a scheme that can effectively improve the decomposition rate of straw and the content of various forms of organic carbon in soil within a short period of time was explored to provide theoretical support for the southern Liaoning.

Integrative Analysis Reveals the Landscape of Hypoxia-Inducible Factor (HIF) Family Genes in Pan-Cancer.

Inside the cancer microenvironment, reduced O2 concentration, termed as hypoxia, is a common phenotype and leads to cancer progression. However, little is known about how and when those HIF members are dysregulated in distinct cancers. Here, by integrating a full range of data of thousands of patients, we comprehensively analyzed the genetics, epigenetics, and transcriptomic level of HIF genes and further defined pathways triggered by disrupted hypoxia-inducible factors. We reveal the expression landscape of HIF family genes and further demonstrate that copy number variations underlie such dysregulation. Further analysis indicates that HIF genes associate with cancer hallmarks such as cell cycle and DNA damage response. Drug resistance analysis showed that HIF globally impacts drug effectiveness such as docetaxel. In summary, the overall analysis reveals the landscape of HIF genes in pan-cancer and may assist mechanism research about hypoxia.

[Yin-yang balance penetrating acupuncture combined with rehabilitation training on upper limb spasticity in stroke hemiplegia].

OBJECTIVE: To compare the therapeutic effect of yin-yang balance penetrating acupuncture combined with rehabilitation training and single rehabilitation training on upper limb spasticity in patients with stroke hemiplegia. METHODS: A total of 60 patients with upper limb spasticity of stroke hemiplegia were randomized into an observation group and a control group, 30 cases in each one. On the basis of conventional western medication, rehabilitation training was adopted in the control group. On the basis of treatment in the control group, yin-yang balance penetrating acupuncture was applied from Jianyu (LI 15) to Binao (LI 14), Quchi (LI 11) to Shaohai (HT 3), Yanglingquan (GB 34) to Yinlingquan (SP 9), Xuanzhong (GB 39) to Sanyinjiao (SP 6), etc. of the affected side in the observation group. The treatment was given once a day, 5 days were as one course, with a 2-day interval between two courses, 4 courses were required in both groups. The classification of modified Ashworth spasticity scale (MAS), surface integrated electromyogram (iEMG) of affected upper limb and the scores of National Institute of Health stroke scale (NIHSS), Fugl-Meyer assessment (FMA) of upper limb and modified Barthel index (MBI) before and after treatment were observed, the therapeutic effect was evaluated in both groups. RESULTS: ①After treatment, the MAS classification reduced in both groups (P<0.05), the cases of grade 0 to Ⅰ+ in the observation group were more than those in the control group (P<0.05); iEMG values of the maximum isometric voluntary contraction of affected usculus biceps brachii, musculus triceps brachii, musculus flexor carpi, musculus extensor carpi, extensor digitorum, aductor pollicis brevis were increased in both groups (P<0.05), and the variations of iEMG of above muscles on the affected side in the observation group were larger than those in the control group (P<0.05). ②After treatment, the scores of NIHSS were decreased (P<0.05), the scores of FMA, MBI were increased in both groups (P<0.05), and the variations of NIHSS, FMA and MBI scores were larger than those in the control group (P<0.05). ③The total effective rate was 93.3% (28/30) in the observation group, which was superior to 70.0% (21/30) in the control group (P<0.05). CONCLUSION: Yin-yang balance penetrating acupuncture combined with rehabilitation training can improve upper limb spasticity, heighten the motor function of upper limb and daily self care in patients with stroke hemiplegia, its therapeutic effect is superior to single rehabilitation training.

[Association of DUSP9 gene polymorphisms with gestational diabetes mellitus].

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of dual specificity phosphatase 9 (DUSP9) gene rs5945326 locus with gestational diabetes mellitus (GDM). METHODS: Genotypes for the rs5945326 locus were determined for 206 pregnant women with GDM (GDM group) and 189 unaffected pregnant women (control group). Allelic and genotypic frequencies of the GDM and control groups were compared. For individuals with various genotypes, the level of blood glucose, serum lipids, and body mass index (BMI) were also compared. RESULTS: The frequencies of AA, AG and GG genotypes for the GDM group were 32.2%, 52.2% and 15.6%, respectively, and 41.2%, 43.9% and 15.0%, for the control group, respectively. No significant difference was detected in the distribution of above genotypes between the two groups (chi-square=3.601, P=0.165). The frequencies of alleles A and G were 58.3% and 41.7% in the GDM group, and 63.1% and 36.9% in the control group, respectively. No significant difference was detected between the two groups too (chi-square=1.894, P=0.188). The high density lipoprotein (HDL) levels of the GG genotype [(2.34×0.61) mmol/L] was significantly higher than that of the AG+AA genotype [(2.06×0.56) mmol/L] (t=2.993, P=0.003). No significant difference was detected in other clinical indexes between the two groups (P> 0.05). CONCLUSION: The SNP rs5945326 in DUSP9 gene may be not associated with the risk of GDM. However, there are correlated with HDL levels.

Vitamin C Prevents Hydrocortisone-Induced Injury in HMEC-1 through Promoting Bestrophin-3 Expression.

OBJECTIVE: To investigate the protective effects and underlying mechanisms of Vitamin C (VC) on hydrocortisone (HC)-induced cell injury in human microvascular endothelial cells (HMEC). METHODS: Cell viability was measured by CCK-8 assay and the expression of Best-3 was detected by Western blotting assay. The experiment was divided into normal control, HC injury group, VC treatment groups, HC + Best-3 siRNA group, HC + VC + Best-3 siRNA group, HC + pcDNA3.1 Best-3 group, and HC + VC + pcDNA3.1 Best-3 group. RESULTS: HC inhibited HMEC-1 cell viability was balanced with lower expression of Best-3 in a dose-dependent manner. Conversely, VC promoted HMEC-1 cell viability was paralleled to higher expression of Best-3 in a dose-dependent manner. Silencing Best-3 with Best-3 siRNA inhibited HMEC-1 cell viability, however, over-expression of Best-3 with pcDNA3.1 Best-3 promoted HMEC-1 cell viability. Moreover, VC and over-expression of Best-3 prevented HC-induced HMEC-1 cell apoptosis; however, silencing Best-3 further enhanced HC-induced HMEC-1 cell apoptosis. HC reduced Best-3 expression, which was alleviated by VC treatment. HC treatment decreased Bcl-2 expression, facilitated Bax expression. Both of VC and over-expression of Best-3 promoted Bcl-2 expression and decreased Bax expression. Additionally, VC and Best-3 expression have a synergistic effect. CONCLUSIONS: VC can efficiently attenuate HC-induced HMEC-1 cell injury, which may be related to promote Best-3 expression.

Upregulation of HIF-1α protects neuroblastoma cells from hypoxia-induced apoptosis in a RhoA-dependent manner.

Hypoxic conditions regulate several metabolic enzymes and transcription factors that are involved in cancer, ischemia and pulmonary diseases. The Ras homolog (Rho) family, including Rho member A (RhoA), is involved in reorganization of the actin cytoskeleton, cell migration and in the regulation of apoptosis and gene transcription. The aim of the present study was to investigate the expression of hypoxia­inducible factor (HIF)­α and the activity of RhoA in PC12 neuroblastoma cells under hypoxic conditions. The upregulation of HIF­α and RhoA by hypoxia was determined using reverse transcription­quantitative polymerase chain reaction and western blot assays, cell apoptosis was analyzed using flow cytometry, and the activity of caspase 3 was examined using a western blot assay and caspase 3 activity assay kit. The PC12 cells were induced to apoptosis following exposure to hypoxia, and exhibited increased expression of HIF­α and increased mRNA and protein expression levels of RhoA. The overexpression of HIF­α attenuated the hypoxia­induced apoptosis of the PC12 cells. In addition, RhoA knockdown using small interfering RNA abrogated the antagonism of HIF­1α towards hypoxia­induced apoptosis. The results of the present study confirmed the protective role of HIF­1α and RhoA in hypoxia­induced PC12 cell apoptosis, and that the upregulation of HIF­1α by hypoxia is RhoA­dependent.

Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system. Galectin-3 (Gal-3) is characterized by a conserved sequence within the carbohydrate recognition domain. The effect of Gal-3 in AD is presently unknown. In this study, we found significantly increased Gal-3 serum levels in patients with AD compared to control participants (P=.017). There was no significant difference between patients with mild cognitive impairment (MCI) and healthy controls (P=.143) or between patients with AD and MCI (P=.688). The degree of cognitive impairment, as measured by the Mini-Mental Status Examination score, was found to have a significant correlation with the Gal-3 serum levels in all patients and healthy controls. These data suggest that Gal-3 potentially plays a role in the neuropathogenesis of AD. The Gal-3 found in serum could be a potential candidate for a biomarker panel for AD diagnosis.

[Effects of electroacupuncture at Jiaji (EX-B 2) on extracellular matrix MMP-1, MMP-3 and TIMP-1 levels in the degenerated cervical intervertebral disc in rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of Jiaji (EX-B 2) on the contents of extracellular matrix metalloproteinase (MMP)-1, MMP-3 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in the cervical intervertebral disc (OIVD) tissue in rats with CIVD degeneration so as to explore its mechanism in relieving intervertebral disc degeneration. METHODS: SD rats were randomized into control (n = 15), model (n = 14), EA (n = 13) and medication (n = 14) groups. CIVO model was established according to Wang's and Shi's method. EA (10/20 Hz, 1 - 3 mA) was applied to Jiaji (EX-B 2) for 10 min, once daily for 30 days. The rats of medication group were fed with Fenbid (15 mg/kg/d) and Jingfukang (0.5 g/kg/d) for 30 days. Extracellular matrix MMP-1, MMP-3 and TIMP-1 levels of the intervertebral disc tissue (C4-6) were detected by ELISA. RESULTS: The contents of MMP-1 and MMP-3 in model group were increased significantly compared with control group (P < 0.05), while TIMP-1 in model group was markedly lower than that of control group (P < 0.05). Compared with model group, both MMP-1 and MMP-3 levels in EA group and MMP-1 in medication group were reduced considerably (P < 0.05), while TIMP-1 of EA group increased significantly (P < 0.05). No significant differences were found between medication and model groups in MMP-3 and TIMP-1 levels (P > 0.05). Under optical microscope, the injured degrees of the fibrous ring and nucleus pulposus, and the outline of the intervertebral disc of both EA and medication groups were evidently lighter than those of model group, but the degeneration severity of the intervertebral disc of EA group was lighter than that of medication group. CONCLUSION: EA of Jiaji (EX-B 2) can effectively relieve the degeneration degree of cervical intervertebral disc in the rat, which is probably related to its effect in regulating extracellular matrix system.