By inhibiting ADCY5, miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture.

To investigate the influence of miR-18a-3p and ADCY5 on OP and osteogenic differentiation of human Mesenchymal stem cell (hBMSCs) and its possible mechanism. Samples were collected from osteoporotic patients with or without vertebral compression fracture, and without OP volunteers. MiR-18a-3p and ADCY5 mRNA expression levels in the tissue samples and hBMSCs during osteogenic differentiation were detected。MiR-18a-3p mimic and OE-ADCY5 were introduced into hBMSCs to research the effects of miR-18a-3p and ADCY5 on osteogenesis differentiation of hBMSCs. Dual luciferase reporter system and RNA pull-down were applied to determine whether ADCY5 was a target gene of miR-18a-3p. Compared with the control group, ADCY5 expression level was down-regulated in patients with OP-no-Frx and OP-Frx, but that of miR-18a-3p was up-regulated. In addition, ADCY5 increased during osteogenesis differentiation of hBMSCs, whereas miR-18a-3p did not. OE-ADCY5 significantly facilitated calcium deposition, ALP activity, osteoblast protein expression (OSX, ALP and EUNX2), miR-18a-3p mimic inhibited osteogenic differentiation, and partially reversed the effect of OE-ADCY5 on osteogenic differentiation. In general, miR-18a-3p targets ADCY5 to promote OP and may be involved in spinal fracturs.

Circular RNA circ-PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-3680-3p in esophageal squamous cell carcinoma.

Circular RNA (circRNA) is a new noncoding RNAs and plays an important role in many pathological processes. Recently, studies have shown that circular RNA_PRKCI (circ-PRKCI) regulates cell proliferation and cell migration of tumor cells. Esophageal carcinoma is a highly malignant digestive tract tumor, which is divided into esophageal adenocarcinoma and esophageal squamous cell carcinoma. In this study, we studied whether circ-PRKCI might influence cell proliferation and cell migration in esophageal squamous cell carcinoma. Quantitative reverse transcription PCR was performed to detect the relative expression of circ-PRKCI in five cases of esophageal squamous cell carcinoma and five cases of paired adjacent normal tissues. RNA immunoprecipitation assay and Luciferase assay confirm the direct interaction between miR-3680-3p and AKT3 or circ-PRKCI. Ethynyldeoxyuridine assays and cell counting Kit-8 were performed to evaluate the effect of miR-3680-3p or circ-PRKCI on cell proliferation, transwell assays were also performed to detect migration in vitro. We found circ-PRKCI is obviously upregulated in esophageal squamous cell carcinoma and upregulation of circ-PRKCI stimulated cell migration and proliferation of ESCC cells. In the mechanism, we confirm that circ-PRKCI, as a molecular sponge of miR-3680-3p, upregulates the expression of AKT. In conclusion, our current studies have been revealing that circ-PRKCI/miR-3680-3p/AKT3 regulatory network plays an important role in esophageal squamous cell carcinoma and that provide new insights into the pathogenesis of esophageal squamous cell carcinoma.

VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with pegylated interferon.

AIM: To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg-IFN) in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: One hundred and nineteen HBeAg-positive CHB patients who received Peg-IFN monotherapy for 48 weeks and then were followed-up for another 48 weeks were prospectively enrolled; baseline 25-hydroxy vitamin D (25-(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped. RESULTS: Forty-five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow-up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294-0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243-0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215-0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203-0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103-0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077-0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634-0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/ ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024-3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057-12.029; P = 0.040). CONCLUSIONS: Genetic variation of VDR rs7975232/ ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg-positive CHB patients with Peg-IFN monotherapy.

Repeatability and Image Quality of IDEAL-IQ in Human Lumbar Vertebrae for Fat and Iron Quantification across Acquisition Parameters.

Echo asymmetry and least square estimation-IQ (IDEAL-IQ) were used to quantify fat and iron to verify the effects of collection parameters on repeatability and image quality of water and fat in human vertebral body. Six IDEAL-IQ sequences were used to scan 48 healthy adult women. Reproducibility of fat and iron quantification and image quality were assessed for six IDEAL-IQ sequences. The results showed that the correlation index (0.987, 0.721) of FF and R2∗ between scans of sequence 2 was higher than that of other sequences, and the consistency of fat quantification was better than that of iron (0.860 vs. 0.579) (P < 0.001). Sequence 2 had the highest image quality score (4.9) and the lowest CV score (9.2%). In the FF figure, SNR (18.8) and CNR (17.8 ± 6.4) were the highest, while CV was the lowest (36.7%, 36.1%). In the R2∗ figure, sequence 3 had the highest SNR (21.8) and CNR (20.5), but its CV (51.8% and 56.1%) was significantly higher than that of sequence 2. The occurrence of fat-water exchange (FWS) was lowest in sequence 2 and sequence 4 (0, N = 96). In conclusion, the fat quantification of IDEAL-IQ was robust to the changes of collection parameters, and section thickness (ST) had a certain effect on maintaining good repeatability of R2∗ quantification. The higher the ST was, the better the image quality of FF and R2∗ was maintained and stable and the less the occurrence of FWS.

MicroRNA miR-18a-3p promotes osteoporosis and possibly contributes to spinal fracture by inhibiting the glutamate AMPA receptor subunit 1 gene (GRIA1).

The promoting role that miR-18a-3p plays in osteoporosis (OP) has been previously described. However, the detailed mechanisms remain unclear. Bone tissues were collected from healthy patients, OP patients, and patients with osteoporotic spinal fractures. An osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) was constructed to detect the expression of miR-18a-3p and glutamate AMPA receptor subunit 1 (GRIA1). Alkaline phosphatase (ALP) activity and a qRT-PCR analysis were used to detect ALP content, alizarin red S staining was used to detect calcium deposition, and qRT-PCR was used to evaluate runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) expression levels. A dual-luciferase reporter and RNA pull-down assay was used to verify the targeted correlation between miR-18a-3p and GRIA1. We observed an increase in miR-18a-3p expression and a decrease in GRIA1 expression in OP and osteoporotic vertebral fracture patients. Upregulation of miR-18a-3p restrained the activity and expression of ALP in hBMSCs, inhibited the expression of RUNX2, OCN, and OPN, and inhibited calcium deposition. Knockdown of miR-18a-3p or upregulation of GRIA1 promoted osteogenic differentiation. Our findings indicate that miR-18a-3p promotes OP progression by regulating GRIA1 expression, suggesting that targeting miR-18a-3p/GRIA1 may be a therapeutic strategy for OP.

Finite element analysis of wedge and biconcave deformity in four different height restoration after augmentation of osteoporotic vertebral compression fractures.

PURPOSE: Biomechanical comparison of wedge and biconcave deformity of different height restoration after augmentation of osteoporotic vertebral compression fractures was analyzed by three-dimensional finite element analysis (FEA). METHODS: Three-dimensional finite element model (FEM) of T11-L2 segment was constructed from CT scan of elderly osteoporosis patient. The von Mises stresses of vertebrae, intervertebral disc, facet joints, displacement, and range of motion (ROM) of wedge and biconcave deformity were compared at four different heights (Genant 0-3 grade) after T12 vertebral augmentation. RESULTS: In wedge deformity, the stress of T12 decreased as the vertebral height in neutral position, flexion, extension, and left axial rotation, whereas increased sharply in bending at Genant 0; L1 and L2 decreased in all positions excluding flexion of L2, and T11 increased in neutral position, flexion, extension, and right axial rotation at Genant 0. No significant changes in biconcave deformity. The stress of T11-T12, T12-L1, and L1-L2 intervertebral disc gradually increased or decreased under other positions in wedge fracture, whereas L1-L2 no significant change in biconcave fracture. The utmost overall facet joint stress is at Genant 3, whereas there is no significant change under the same position in biconcave fracture. The displacement and ROM of the wedge fracture had ups and downs, while a decline in all positions excluding extension in biconcave fracture. CONCLUSIONS: The vertebral restoration height after augmentation to Genant 0 affects the von Mises stress, displacement, and ROM in wedge deformity, which may increase the risk of fracture, whereas restored or not in biconcave deformity.

Clinical Features and Short-Term Outcomes in COVID-19-Infected Patients with Cancer.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer. METHODS: We performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups. RESULTS: A total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes. CONCLUSION: Peripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.

Standard-dose epirubicin increases the pathological complete response rate in neoadjuvant chemotherapy for breast cancer: a multicenter retrospective study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has become the best comprehensive treatment choice for breast cancer. Epirubicin is a crucial drug widely used in breast cancer chemotherapy, but it is often used with a reduced dosage in NAC for Chinese patients for its notable cardiotoxicity and frequent adverse events. This study aimed to investigate the efficacy and safety of standard-dose epirubicin in NAC for Chinese breast cancer patients retrospectively. METHODS: We retrospectively collected clinicopathological parameters of breast cancer patients who underwent epirubicin-based NAC and a later surgery from three separate medical centers. Patients were divided into standard-dose and low-dose groups according to the epirubicin dose. The pathological complete response (pCR) rate, as the main therapeutic outcomes, and the incidence of adverse events were recorded and compared. RESULTS: The pCR rate of the standard-dose group was 41.2%, while the low-dose group was 10.1% (P<0.001). The univariate analysis showed that ER status (HR, 2.519; 95% CI, 1.057-5.988, P=0.037) and epirubicin dose (HR, 6.200; 95% CI, 2.374-16.193, P<0.001) were associated with pCR rates. The multivariate analysis showed that patients receiving standard-dose epirubicin chemotherapy (HR, 6.925; 95% CI, 2.537-18.902, P<0.001) showed more possibility to achieve pCR after NAC. There was no significant difference in the incidence rates of grade III/IV adverse events between these two different dose groups. CONCLUSIONS: Standard-dose epirubicin increases the pCR rate in breast cancer patients treated with NAC, and no other toxicity is noted.

Prognostic Significance Of Platelet-To-Lymphocyte Ratio (PLR) And Mean Platelet Volume (MPV) During Etoposide-Based First-Line Treatment In Small Cell Lung Cancer Patients.

BACKGROUND: Small cell lung cancer (SCLC) is a special type of lung cancer and it is responsive to chemotherapy. Blood parameters have been proved to be associated with survival for many types of malignancies. This study aimed to investigate the prognostic significance of platelet-to-lymphocyte ratio (PLR) and mean platelet volume (MPV) for SCLC patients with etoposide-based first-line treatment. METHODS: We retrospectively identified 138 patients diagnosed as SCLC who underwent etoposide-based first-line chemotherapy. The patients' baseline clinical characteristics and blood parameters were collected. Kaplan-Meier analysis and Cox regression methods were used to determine the factors associated with progression-free survival (PFS). RESULTS: The optimal cut-off value of diagnosis was depended on the ROC curve, the cut-off value of pretreatment PLR was 190 (sensitivity 39.0%, specificity 88.5%), and the cut-off value of pretreatment MPV was 10.0 (sensitivity 60.7%, specificity 61%). Kaplan-Meier analysis showed patients with high PLR levels in baseline had worse PFS than those with low PLR levels (P <0.001). Multivariate analysis revealed pretreatment MPV was an independent prognostic factor for PFS (HR: 0.815, 95% CI: 0.711-0.933, P =0.003). Further research suggested continuous high PLR indicated a poor therapy outcome (P =0.002). CONCLUSION: Pretreatment MPV can be an independent predictor for first-line treatment outcome and a continuously high level of PLR suggested inferior PFS in etoposide-treated SCLC patients.

A six-microRNA signature to predict outcomes of patients with gastric cancer.

Gastric cancer (GC) is a common gastrointestinal tumor with poor prognosis. However, conventional prognostic factors cannot accurately predict the outcomes of GC patients. Therefore, there remains a need to identify novel predictive markers to improve prognosis. In this study, we obtained microRNA expression profiles of 385 GC patients from The Cancer Genome Atlas. We performed Cox regression analysis to identify overall survival-related microRNA and then constructed a microRNA signature-based prognostic model. The accuracy of the model was evaluated and validated through Kaplan-Meier survival analysis and time-dependent receiver operating characteristic (ROC) curve analysis. The independent prognostic value of the model was assessed by multivariate Cox regression analysis. Enrichment analysis was performed to explore potential functions of the prognostic microRNA. Finally, a prognostic model based on a six-microRNA (miRNA-100, miRNA-374a, miRNA-509-3, miRNA-668, miRNA-549, and miRNA-653) signature was developed. Further analysis in the training, test, and complete The Cancer Genome Atlas set showed the model can distinguish between high-risk and low-risk patients and predict 3-year and 5-year survival. The six-microRNA signature was also an independent prognostic marker, and enrichment analysis suggested that the microRNA may be involved in cell cycle and mitosis. These results demonstrated that the model based on the six-microRNA signature can be used to accurately predict the prognosis of GC patients.