Identification of ROS and KEAP1-related genes and verified targets of α-hederin induce cell death for CRC.

In this study, we analyzed and verified differentially expressed genes (DEGs) in ROS and KEAP1 crosstalk in oncogenic signatures using GEO data sets (GSE4107 and GSE41328). Multiple pathway enrichment analyses were finished based on DEGs. The genetic signature for colorectal adenocarcinoma (COAD) was identified by using the Cox regression analysis. Kaplan-Meier survival and receiver operating characteristic curve analysis were used to explore the prognosis value of specific genes in COAD. The potential immune signatures and drug sensitivity prediction were also analyzed. Promising small-molecule agents were identified and predicted targets of α-hederin in SuperPred were validated by molecular docking. Also, expression levels of genes and Western blot analysis were conducted. In total, 48 genes were identified as DEGs, and the hub genes such as COL1A1, CXCL12, COL1A2, FN1, CAV1, TIMP3, and IGFBP7 were identified. The ROS and KEAP1-associated gene signatures comprised of hub key genes were developed for predicting the prognosis and evaluating the immune cell responses and immune infiltration in COAD. α-hederin, a potential anti-colorectal cancer (CRC) agent, was found to enhance the sensitivity of HCT116 cells, regulate CAV1 and COL1A1, and decrease KEAP1, Nrf2, and HO-1 expression significantly. KEAP1-related genes could be an essential mediator of ROS in CRC, and KEAP1-associated genes were effective in predicting prognosis and evaluating individualized CRC treatment. Therefore, α-hederin may be an effective chemosensitizer for CRC treatments in clinical settings.

Nomogram to predict severe retinopathy of prematurity in Southeast China.

AIM: To define the predictive factors of severe retinopathy of prematurity (ROP) and develop a nomogram for predicting severe ROP in southeast China. METHODS: Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children's Hospital were included. Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively. Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction, which was compared with WINROP model and Digirop-Birth model. RESULTS: Infants from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (n=478) were randomly allocated into training (n=402) and internal validation group (n=76). Infants from Taizhou Women and Children's Hospital were set as external validation group (n=76). Severe ROP were found in 52 of 402 infants, 12 of 76 infants, and 7 of 76 infants in training group, internal validation group, and external validation group, respectively. Birth weight [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.996-0.999; P<0.001], multiple births (OR, 1.885; 95%CI, 1.013-3.506; P=0.045), and non-invasive ventilation (OR, 0.288; 95%CI, 0.146-0.570; P<0.001) were identified as predictive factors for the prediction of severe ROP, by univariate analysis and multivariate analysis. For predicting severe ROP based on the internal validation group, the areas under receiver operating characteristic curve (AUC) was 78.1 (95%CI, 64.2-92.0) for the nomogram, 32.9 (95%CI, 15.3-50.5) for WINROP model, 70.2 (95%CI, 55.8-84.6) for Digirop-Birth model. In external validation group, AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model (80.2 versus 51.1 and 63.4). The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model. The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability. CONCLUSION: Birth weight, multiple births, and non-invasive ventilation are independent predictors of severe ROP. The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China.

Exploring the anatomical factors influencing testes elasticity via ultrasound shear wave elastography: Preliminary results

Purpose: The aim of this study is to evaluate the anatomical factors influencing elasticity values of normal testicular parenchyma using shear wave elastography (SWE). Methods: This study examined 68 healthy male volunteers (117 testes in which standard transverse axis ultrasonography views could be obtained) via conventional scrotal ultrasonography and SWE. Both the mean (EMean) and standard deviation (ESD) elasticity values were acquired. Results: In the standard transverse axis view of the rete testis at the mid-lateral edge of the testes, the EMean values in 2mm the testicular parenchyma from the rete testis and the testicular capsule at the same level as the rete testis were all significantly larger than in the central zone (P<0.001, P<0.001, respectively). The EMean value in the testicular parenchyma 2mm from the testicular capsule on the line formed approximately 45° below the horizontal line of the rete testis was significantly larger than in the rete testis approximately 45° above the horizontal line (P<0.001). In two standard transverse axis views, the ESD values in other regions were significantly larger than those in the central zones (all P<0.001). Also, the EMean values in the transmediastinal arteries were larger than those of the surrounding normal testicular parenchyma (P<0.001). Conclusion: Based on SWE, factors including the testicular capsule, the density of testicular fibrous septa, the depth of the Q-Box™, and the transmediastinal artery may influence the testes elasticity measurement. (AU)

Exploring the anatomical factors influencing testes elasticity via ultrasound shear wave elastography: Preliminary results.

PURPOSE: The aim of this study is to evaluate the anatomical factors influencing elasticity values of normal testicular parenchyma using shear wave elastography (SWE). METHODS: This study examined 68 healthy male volunteers (117 testes in which standard transverse axis ultrasonography views could be obtained) via conventional scrotal ultrasonography and SWE. Both the mean (EMean) and standard deviation (ESD) elasticity values were acquired. RESULTS: In the standard transverse axis view of the rete testis at the mid-lateral edge of the testes, the EMean values in 2mm the testicular parenchyma from the rete testis and the testicular capsule at the same level as the rete testis were all significantly larger than in the central zone (P<0.001, P<0.001, respectively). The EMean value in the testicular parenchyma 2mm from the testicular capsule on the line formed approximately 45° below the horizontal line of the rete testis was significantly larger than in the rete testis approximately 45° above the horizontal line (P<0.001). In two standard transverse axis views, the ESD values in other regions were significantly larger than those in the central zones (all P<0.001). Also, the EMean values in the transmediastinal arteries were larger than those of the surrounding normal testicular parenchyma (P<0.001). CONCLUSION: Based on SWE, factors including the testicular capsule, the density of testicular fibrous septa, the depth of the Q-Box™, and the transmediastinal artery may influence the testes elasticity measurement.

Triterpenoids of Rhus chinensis Supressed Colorectal Cancer Progress by Enhancing Antitumor Immunity and CD8 + T Cells Tumor Infiltration.

The absence of CD8+ T cells in the tumor center has become a major obstacle in the immunotherapy of colorectal cancer. Therefore, new therapeutic strategies are urgently needed to promote the accumulation of CD8+ T cells in the tumor center. Previous studies have shown that triterpenoid of Rhus chinensis (TER) is involved in the proliferation and apoptosis of colorectal cancer cells, and can regulate their immune activity, but its mechanism needs to be further elucidated. In this study, the antitumor effect and adaptive immune response of TER on tumor-bearing mice were evaluated and compared with 5-fluorouracil. The results showed that TER could significantly inhibit tumor growth and prolong the survival time of tumor-bearing mice. The In Vivo studies have shown that TER can not only enhance antitumor immunity and promote the accumulation of CD8 + T cells to tumor sites, but also inhibit tumor progression by regulating the expression of PD-1 and PD-L1 and significantly reducing the mortality of mice. Our study demonstrated for the first time that TER has oncolytic effect, and recruited adaptive immune cells to enhance the efficacy of anti-PD-1/PD-L1 in colorectal cancer, which provides a potential therapeutic target for combined immunotherapy of colorectal cancer.

Diagnostic Accuracy of Three-Dimensional Endoanal Ultrasound for Anal Fistula: A Systematic Review and Meta-analysis.

BACKGROUND: Anal fistula is a relatively common anorectal disease. An accurate assessment of the main anal fistula type and the anatomy of the internal opening before surgery is necessary to obtain the best surgical results. Whether three-dimensional endoanal ultrasound (3D-EAUS) should be used as the first-line diagnostic tool for anal fistula is still controversial. The purpose of this study is to conduct a meta-analysis of the published literature on 3D-EAUS and anal fistula, and compare the results of 3D-EAUS and surgery to evaluate the diagnostic value of 3D-EAUS for anal fistula. METHODS: An online search of databases in English included PubMed, Embase, and Cochrane Library. After the diagnostic accuracy of 3D-EAUS of all anal fistula types was integrated, a single-group rate meta-analysis was performed; we analyzed 3D-EAUS separately for the diagnosis of different anal fistula types, and conducted a meta-analysis of test accuracy. The analysis combined sensitivity, specificity, and the respective 95% CI, to draw a summary receiver operating characteristic curve (SROC), and estimate the area under curve (AUC). RESULTS: Based on the inclusion criteria, we selected 8 studies covering 1057 cases of anal fistula and 548 cases of internal opening. The meta-analysis data show that 3D-EAUS has a total accuracy rate of 91% (95% CI, 88-94%). It has high sensitivity and specificity for different anal fistula classifications. The SROC curves for anal fistula internal openings were plotted, and the AUC was calculated to be 0.86 (95% CI, 0.83-0.89). CONCLUSIONS: 3D-EAUS can be used as the first-line diagnostic tool for anal fistula, because it has a high diagnostic accuracy for most anal fistulas. However, due to the insufficient diagnostic accuracy of 3D-EAUS for complex fistulas, 3D-EAUS combined with MRI examination can be used to more accurately detect the secondary extension of complex fistulas, so as to describe the complete anatomy of the fistula in more detail.

Treatment effect and mechanism of Fu's subcutaneous needling among patients with shoulder pain: A retrospective pilot study.

Fu's subcutaneous needling (FSN) is a new acupuncture therapy developed from acupuncture and Traditional Chinese Medicine models. The aim of this study was to investigate the effect of FSN on shoulder pain. In this retrospective comparative study, patient case files with shoulder pain (Group A) treated with FSN were analyzed and compared with the same number of patients with shoulder pain (Group B) treated with conventional acupuncture and physical therapy. Motion-related pain (MRP), pain under pressure (PUP), and Range of motion (ROM) were collected before and after intervention. In the 68 patients, there were 39 males and 29 females, aged 21-53 years old (mean ± SD = 36.4 ± 8.15) with onset time ranging from 1 day to 7 days (mean ± SD = 3.15 ± 1.73). MRP, PUP, and ROM scores were improved after FSN intervention (p < .05). There were significant differences between group A and group B in MRP, PUP, and ROM scores after FSN intervention and 1 week follow-up (p < .05). No adverse events, such as fainting and sharp pain, occurred during the treatment process. FSN can be an effective rehabilitation intervention for improving shoulder pain and shoulder range of motion.

Effects and mechanisms of fatty acid metabolism­mediated glycolysis regulated by betulinic acid­loaded nanoliposomes in colorectal cancer.

Although previous studies have demonstrated that triterpenoids, such as betulinic acid (BA), can inhibit tumor cell growth, their potential targets in colorectal cancer (CRC) metabolism have not been systematically investigated. In the present study, BA­loaded nanoliposomes (BA­NLs) were prepared, and their effects on CRC cell lines were evaluated. The aim of the present study was to determine the anticancer mechanisms of action of BA­NLs in fatty acid metabolism­mediated glycolysis, and investigate the role of key targets, such as acyl­CoA synthetase (ACSL), carnitine palmitoyltransferase (CPT) and acetyl CoA, in promoting glycolysis, which is activated by inducing hexokinase (HK), phosphofructokinase­1 (PFK­1), phosphoenolpyruvate (PEP) and pyruvate kinase (PK) expression. The results demonstrated that BA­NLs significantly suppressed the proliferation and glucose uptake of CRC cells by regulating potential glycolysis and fatty acid metabolism targets and pathways, which forms the basis of the anti­CRC function of BA­NLs. Moreover, the effects of BA­NLs were further validated by demonstrating that the key targets of HK2, PFK­1, PEP and PK isoenzyme M2 (PKM2) in glycolysis, and of ACSL1, CPT1a and PEP in fatty acid metabolism, were blocked by BA­NLs, which play key roles in the inhibition of glycolysis and fatty acid­mediated production of pyruvate and lactate. The results of the present study may provide a deeper understanding supporting the hypothesis that liposomal BA may regulate alternative metabolic pathways implicated in CRC adjuvant therapy.

The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

OBJECTIVE: To study the effect of intermittent hypoxia training (IHT) for migraine. DESIGN: A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital. METHODS: Participants with migraines were randomly assigned to two groups (IHT group and control group). The Migraine Disability Assessment (MIDAS), Visual Analog Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and cerebrovascular hemodynamic parameters were collected at baseline and end of the 8th week. The attack frequencies of migraines were evaluated at 3 months. RESULTS: Among the 48 subjects, five males and forty-three females, the ages ranged from 19 to 53 years old (mean ± SD = 31.3±7.78). MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters were improved after IHT intervention. There were significant differences between IHT group and the control group in MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters at the end of the 8th weeks (P<0.05). Attack frequencies were improved within 3 months after IH training intervention (P<0.01), but not in the control group (P>0.05). No adverse events occurred during the study. CONCLUSION: IHT could improve migraines after intervention up to three months. IHT could be an effective method for relieving a migraine.

Randomized Trial on Comparison of the Efficacy of Extracorporeal Shock Wave Therapy and Dry Needling in Myofascial Trigger Points.

OBJECTIVE: The aim of the study was to compare the efficacy of radial extracorporeal shock wave therapy and dry needling in the treatment of myofascial trigger points in the upper trapezius muscle. DESIGN: A total of 65 patients with myofascial trigger points were randomly divided into extracorporeal shock wave therapy group (n = 32) and dry needling group (n = 33). Patients received 3 wks of treatment at 1-wk intervals (in both groups). Visual analog scale, pressure pain threshold, Neck Disability Index, and shear modulus were evaluated before treatment, immediately after the first therapy, 1 mo, and 3 mos after the completion of the third therapy. RESULTS: Significant improvements of visual analog scale, pressure pain threshold, and Neck Disability Index scores were observed at all time points after treatment (P < 0.01) in both treatment groups. The shear modulus of myofascial trigger points was reduced in both dry needling group (P < 0.05) and extracorporeal shock wave therapy group (P < 0.01) immediately after the first treatment. Significant reductions in shear modulus were maintained up to 3-mo posttreatment in both groups (P < 0.01). There were no significant differences between the radial extracorporeal shock wave therapy group and dry needling group. CONCLUSIONS: The extracorporeal shock wave therapy is as effective as dry needling for relieving pain, improving function, and reducing shear modulus for patients with myofascial trigger points after a series of three treatments.