High SNRPA1 expression leads to poor prognosis in patients with lung adenocarcinoma.

OBJECTIVE: SNRPA1, a subunit of spliceosome complex, has been implicated in diverse cancers, while its biological effect in LUAD remains elusive. Therefore, we sought to decipher the relationship between SNRPA1 expression and the prognosis of patients with LUAD and reveal the underlying molecular mechanism. MATERIALS AND METHODS: Based on the clinical data from TCGA databases, the multivariate Cox model was constructed to screen the prognostic value of SNRPA1. qRT-PCR and immunohistochemical staining were used to examine SNRPA1 mRNA and protein expression in LUAD. The effect of SNRPA1 on LUAD cell proliferation, migration, and epithelial mesenchymal transformation were examined using colony formation assays, wound healing, and western blot assays, respectively. Finally, the influence of SNRPA1 on LUAD immune microenvironment were validated from the Tumor Immune Estimation Resource database. RESULTS: SNRPA1 was significantly upregulated in both LUAD tissues and cell lines, and highly expressed SNRPA1 contributed to poor prognosis of LUAD patients. In vitro, SNRPA1 knockdown inhibited the proliferation and migration, as well as delayed the EMT differentiation of LUAD cells. Lastly, SNRPA1 was found to be positively associated with immune infiltration and some immune-check-point markers. CONCLUSIONS: Our findings indicate that SNRPA1 may be a new biomarker for prognostic prediction and a potential therapeutic target in the treatment of LUAD.

Construction of a fatty acid metabolism-related gene signature for predicting prognosis and immune response in breast cancer.

Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity. Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism. Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA-transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan-Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models. Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients. Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

Minimally invasive open reduction of greater tuberosity fractures by a modified suture bridge procedure.

BACKGROUND: Most greater tuberosity fractures can be treated without surgery but some have a poor prognosis. The surgical procedures for avulsion fractures of the humeral greater tuberosity include screw fixation, suture anchor fixation, and plate fixation, all of which have treatment-associated complications. To decrease surgical complications, we used a modified suture bridge procedure under direct vision and a minimally invasive small incision to fix fractures of the greater tuberosity of the humerus. AIM: To investigate the clinical efficacy and outcomes of minimally invasive modified suture bridge open reduction of greater tuberosity evulsion fractures. METHODS: Sixteen patients diagnosed between January 2016 and January 2019 with an avulsion-type greater tuberosity fracture of the proximal humerus and treated by minimally invasive open reduction and modified suture bridges with anchors were studied retrospectively. All were followed up by clinical examination and radiographs at 3 and 6 wk, 3, 6 and 12 mo after surgery, and thereafter every 6 mo. Outcomes were assessed preoperatively and postoperatively by a visual analog scale (VAS), the University of California Los Angeles (UCLA) shoulder score, the American Shoulder and Elbow Surgeon score (ASES), and range of motion (ROM) for shoulders. RESULTS: Seven men and nine women, with an average age of 44.94 years, were evaluated. The time between injury and surgery was 1-2 d, with an average of 1.75 d. The mean operation time was 103.1 ± 7.23 min. All patients achieved bone union within 3 mo after surgery. VAS scores were significantly decreased (P = 0.002), and the mean degrees of forward elevation (P = 0.047), mean degrees of abduction (P = 0.035), ASES score (P = 0.092) were increased at 3 wk. The UCLA score was increased at 6 wk (P = 0.029) after surgery. The average degrees of external rotation and internal rotation both improved at 3 mo after surgery (P = 0.012 and P = 0.007, respectively). No procedure-related deaths or incision-related superficial or deep tissue infections occurred. CONCLUSION: Modified suture bridge was effective for the treatment of greater tuberosity evulsion fractures, was easier to perform, and had fewer implants than other procedures.

MiR-205-5p promotes lung cancer progression and is valuable for the diagnosis of lung cancer.

BACKGROUND: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis. MATERIALS AND METHODS: MiR-205-5p was detected by quantitative real-time PCR. The effect of miR-205-5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR-205-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. RESULTS: The miR-205-5p was increased in lung cancer tissues. MiR-205-5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3' untranslated region, miR-205-5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR-205-5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR-205-5p in the diagnosis of non-small-cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer. CONCLUSIONS: MiR-205-5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR-205-5p is a novel and valuable biomarker for lung cancer diagnosis.

The Treatment of Subtrochanteric Fracture with Reversed Contralateral Distal Femoral Locking Compression Plate (DF-LCP) Using a Progressive and Intermittent Drilling Procedure in Three Osteopetrosis Patients.

OBJECTIVE: To describe the application of reversed contralateral distal femoral locking compression plate (DF-LCP) inserted through a progressive and intermittent drilling procedure in the treatment of osteopetrotic subtrochanteric fracture (OSF). METHODS: Three patients (one male and two females with an average age of 45.33 ± 11.09 years) with OSF hospitalized between September 2015 and September 2020, were included in this present study. Lateral approach was applied in all patients who accepted open reduction and internal fixation (ORIF) with a reversed contralateral DF-LCP inserted through a progressive and intermittent drilling procedure. The operation time and intraoperative blood loss were recorded to evaluate the efficiency of this surgical method. Physical examination and imaging examination of the fracture site were used to evaluate the fracture union status, the position and stability of the implant, and the alignment of the injured limb at 1, 3, 6, and 12 months after operation, then a subsequent visit was conducted at least once a year. Harris Hip Score (HHS) was used to evaluate the hip joint function at 6 and 12 months after operation. RESULTS: The average operation time was 140 ± 21.60 min (110, 160, and 150 min); The average intraoperative blood loss was about 333.33 ± 23.57 ml (300, 350, and 350 ml). The average follow-up time was 22.33 ± 7.41 months (29, 26, and 12 months). All patients achieved bone union with an average time of 6.67 ± 0.94 months (6, 8, and 6 months). At the time of 6 months after operation, case 1 and 3 were almost pain-free and could walk with full weight bearing while case 2 could walk only with partial weight bearing using a crutch. The HHS scores of cases 1, 2, and 3 were 84/100, 74/100, and 92/100, respectively. At the follow-up at 12 months after operation, the HHS score improved to 91/100, 81/100, and 96/100, respectively. The contralateral incomplete old subtrochanteric fracture was deteriorated in case 1 at 26 months after operation. After 3 months of limited weight bearing using a crutch, bone union was verified in radiograph imaging. Fresh contralateral subtrochanteric fracture occurred in case 2 at 26 months after operation, which was treated using a similar surgical approach, and its clinical outcome is under follow-up. Moreover, no perioperative complications including operation-related death, vascular/nerve injury, deep venous thrombosis, pulmonary embolism, and incision infection, and long-term complications involving malunion, nonunion, implant failure, ankylosis, heterotopic ossification, osteonecrosis, and osteomyelitis were identified. CONCLUSION: The application of reversed contralateral DF-LCP in OSF is practicable and reliable. Progressive and intermittent drilling is a safe and efficient method for implant insertion in this complicated situation.

Polysaccharides from Ulva prolifera O.F. Müller inhibit cell proliferation via activating MAPK signaling in A549 and H1650 cells.

Reactive oxygen species (ROS), especially hydrogen peroxide (H2O2), have recently been reported to cause a significant increase in the production and expression of matrix metalloproteinases (MMPs), which are closely correlated with lung cancer metastasis. The aim of the present study is to determine the inhibitory effects of a polysaccharide isolated from Ulva prolifera O.F. Müller (U. prolifera) on the invasive potential of non-small cell lung cancer (NSCLC) cells, and further to explore the underlying mechanisms connected to that potential. The data showed that increased MMP-9 resulting from H2O2 exposure was mediated by activating mitogen-activated protein kinases (MAPKs). Pre-treatment with polysaccharides suppressed the activation of H2O2-mediated MAPK pathways and cell invasion. Hence, MMP-9 production triggered by H2O2 was demonstrated by activating MAPK signaling in a Myc-dependent manner. Taken together, these results suggested that polysaccharides suppress H2O2-induced cell invasion by inhibiting Myc-mediated MMP-9 gene transcription through the MAPK signaling pathway in A549 and NCI-H1650 cells. Our data also suggested that polysaccharides may be useful in minimizing the development of lung cancer metastasis. In the future, pretreatment with polysaccharides because of their antioxidant properties might be beneficial to enhance surgical outcomes.

Comparison of the clinical efficacy of AcrySof® IQ and TECNIS® toric intraocular lenses: A real-world study.

Corneal astigmatism significantly compromises uncorrected visual acuity (UCVA) after phacoemulsification with implantation of traditional spherical or non-spherical monofocal intraocular lens (IOL). Toric IOL provides an effective way to gain favorable postoperative UCVA for the patients with cataracts with corneal astigmatism. There are numerous types of toric IOLs; however AcrySof® IQ toric IOL (Alcon Laboratories, Inc.) and TECNIS® toric IOL (Johnson & Johnson Vision; Johnson & Johnson) are most frequently used in our clinical practice. The purpose of the current study was to compare the clinical efficacy of AcrySof IQ with TECNIS toric IOL implantation, and to provide a clinical basis on selecting an appropriate toric IOL before cataract surgery for patients with corneal astigmatism. A total of 30 patients with cataract (44 eyes) with corneal astigmatism [0.82-7.27 diopters (D)], who have undergone phacoemulsification with toric IOL implantation between October 2012 and December 2017, were included in the current retrospective cohort study. Patients were divided into two groups: One group (26 eyes) received the AcrySof IQ toric IOL (AcrySof group) and the other group (18 eyes) received the TECNIS toric IOL (Tecnis group). The indexes of curative effect, such as uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively), refractive outcomes, contrast sensitivity (CS), IOL rotation, and satisfaction, were evaluated. Both toric IOLs significantly improved UDVA and CDVA. Postoperative mean residual astigmatism was similar in the AcrySof group and in the Tecnis group (0.75±0.50 and 0.78±0.90 D; P=0.896). There was no statistically significant between postoperative CS in the AcrySof and Tecnis groups. Rotations of >10˚ were considered to be significant and were identified in three eyes. The mean IOL rotation showed no statistically significant difference (AcrySof group, 0.24±5.54˚; Tecnis group, -0.19±6.28˚; P=0.416). The mean patient satisfaction score was 8.46±1.21 in the AcrySof group and 8.78±1.44 in the Tecnis group (P=0.260). The results of the current study indicated that patients with cataracts with corneal astigmatism undergoing phacoemulsification with AcrySof IQ and TECNIS toric IOL implantation achieved similar clinical efficacy in term of visual outcomes, refraction correction, CS, rotational stability and satisfaction.

Roles of HOTAIR in lung cancer susceptibility and prognosis.

BACKGROUND: Long noncoding (lncRNA) single-nucleotide polymorphisms (SNPs) are associated with the susceptibility to the development of various malignant tumors. The aim of this study was to investigate the roles of HOX transcript antisense intergenic RNA (HOTAIR) and its SNPs in lung cancer. METHODS: Initially, the expression of HOTAIR in different tumors was investigated using the online Gene Expression Profiling Interactive Analysis (GEPIA) resource. Three SNPs (rs920778, rs1899663, and rs4759314) of HOTAIR were identified using the MassArray system. Following this, the relationship between these SNPs and susceptibility to lung cancer was investigated. RESULTS: Expression of HOTAIR was found to increase in a variety of cancers, including nonsmall cell lung cancer (NSCLC). We found that the genotypes of these SNPs (rs920778, rs1899663, and rs4759314) were not significantly associated with lung cancer type, family history, lymph node metastasis, or lung cancer stage. In gender stratification, the results of rs920778 genotypes showed that, compared to genotype AA, the AG (OR = 0.344, 95% CI: 0.133-0.893, p = .028) and AG + GG (OR = 0.378, 95% CI: 0.153-0.932, p = .035) genotypes of rs920778 are protective factors against NSCLC in females. In smoking stratification, compared with AA of rs920778, the genotype AG + GG (OR = 0.507, 95% CI: 0.263-0.975, p = .042) was a protective factor against NSCLC in nonsmoking people. No statistical differences were observed in the classifications of rs1899663 and rs4759314 genotypes. Linkage disequilibrium analysis revealed a high linkage disequilibrium between the rs920778 and rs1899663 (D' = 0.99, r2  = .74), rs920778 and rs4759314 (D' = 0.85, r2  = .13), and rs1899663 and rs4759314 (D' = 0.79, r2  = .00). CONCLUSION: Our study demonstrated that HOTAIR expression increased in NSCLC, and that the genotypes of rs920778 could be useful in the diagnosis and prognosis of lung cancer.

Immune biomarkers alterations in post-traumatic stress disorder: A systematic review and meta-analysis.

BACKGROUND: Studies have reported the changes of immune biomakers in post-traumatic stress disorder (PTSD), but the results were conflicting. Our aim was to investigate the changes of immune biomarkers in PTSD. METHODS: Literatures investigating the changes of immune markers in PTSD published in English were systematically searched through PubMed, Embase and Web of Science. We conducted random effects meta-analyses relating PTSD to immune biomarker concentrations and using subgroup analyses to resolve heterogeneity. RESULTS: A total of 2606 articles were screened and 42 samples were included by the systematic review. The levels of interleukin-1ß (IL-1ß, P = 0.01), IL-2 (P = 0.006), IL-6 (P = 0.0002), interferon-γ (IFN-γ, P = 0.004), tumor necrosis factor-α (TNF-α, P = 0.004), C-reactive protein (CRP, P = 0.0003) and white blood cell (WBC, P = 0.01) were higher in PTSD than healthy controls (HC). Subgroup meta-analyses for psychotropic medication showed the levels of IL-1ß and IL-2 were not increased in the PTSD. Subgroup meta-analyses for whether HC exposed to trauma showed the levels of IL-1ß and IL-6 were not increased in the PTSD. Egger´s test revealed there was no publication bias. However, there was significant heterogeneity across studies for immune markers other than for WBC (P = 0.14, I2 = 45%). Subgroup analyses based on sex, HC exposed to trauma, PTSD comorbid major depressive disorder, PTSD on psychotropic medications partially or completely resolved heterogeneity for some immune biomarkers. CONCLUSION: This meta-analysis provides evidence for elevation of IFN-γ, TNF-α, CRP, and WBC in PTSD.

Comparison of visual outcomes with implantation of trifocal versus bifocal intraocular lens after phacoemulsification: a Meta-analysis.

AIM: To compare a trifocal intraocular lens (IOL) and a bifocal IOL implantation in improving visual function after cataract surgery. METHODS: Eligible literatures were systematically searched through EMBASE and PubMed databases. The inclusion criteria were prospective comparative clinical trials on cataract surgery comparing trifocal IOL with bifocal IOL implantation that assessed visual acuity, contrast sensitivity and subjective vision quality. The effects were computed as standardized mean differences and pooled using fixed-effect or random-effect models. RESULTS: Four prospective randomized controlled trials (RCTs) and five cohorts provided data were included by a systematic review, comprising 265 eyes implanted with trifocal IOLs and 264 eyes implanted with bifocal IOLs. Monocular distance visual acuity (VA) showed a statistically significant but small difference that favored trifocal IOLs (MD=-0.06; 95%CI, -0.10 to -0.02; Z=2.90, P=0.004 for uncorrected distance VA, and MD= -0.02; 95%CI, -0.03 to -0.00; Z=2.02, P=0.04 for corrected distance VA), but the data did not suggest that the effect of trifocal IOL implantation would clinically outperform bifocal IOL implantation. There was no significant difference in monocular near VA (MD=-0.01; 95%CI, -0.07 to 0.04; Z=0.42, P=0.68 for distance-corrected near VA, and MD=-0.01; 95%CI, -0.06 to 0.03; Z=0.55, P=0.58 for corrected near VA) or refraction between two groups. Contrast sensitivity and subjective visual quality had no conclusive results. CONCLUSION: All results indicate that trifocal IOL and bifocal IOL had similar levels of monocular distance and near VA.

AC1MMYR2 impairs high dose paclitaxel-induced tumor metastasis by targeting miR-21/CDK5 axis.

Paclitaxel (taxol) is a widely used chemo-drug for many solid tumors, while continual taxol treatment is revealed to stimulate tumor dissemination. We previously found that a small molecule inhibitor of miR-21, termed AC1MMYR2, had the potential to impair tumorigenesis and metastasis. The aim of this study was to investigate whether combining AC1MMYR2 with taxol could be explored as a means to limit tumor metastasis. Here we showed that abnormal activation of miR-21/CDK5 axis was associated with breast cancer lymph node metastasis, which was also contribute to high dose taxol-induced invasion and epithelial mesenchymal transition (EMT) in both breast cancer cell line MDA-MB-231 and glioblastoma cell line U87VIII. AC1MMYR2 attenuated CDK5 activity by functional targeting CDK5RAP1, CDK5 activator p39 and target p-FAK(ser732). A series of in vitro assays indicated that treatment of AC1MMYR2 combined with taxol suppressed tumor migration and invasion ability in both MDA-MB-231 and U87VIII cell. More importantly, combination therapy impaired high-dose taxol induced invadopodia, and EMT markers including ß-catenin, E-cadherin and vimentin. Strikingly, a significant reduction of lung metastasis in mice was observed in the AC1MMYR2 plus taxol treatment. Taken together, our work demonstrated that AC1MMYR2 appeared to be a promising strategy in combating taxol induced cancer metastasis by targeting miR-21/CDK5 axis, which highlighted the potential for development of therapeutic modalities for better clinic taxol application.