Gelanxinning capsule improves coronary microvascular dysfunction by inhibiting inflammation and restoring endothelial function.

OBJECTIVE: Gelanxinning capsule (GXSC) is a Chinese medicine to cure coronary artery disease (CAD) and a compound of Pueraria lobata, hawthorn extract, and gypenosides. However, whether GXSC could improve coronary microvascular dysfunction (CMD) is unknown. We aimed to demonstrate the therapeutic effect of GXSC on CMD and its underlying mechanisms in CAD patients. PATIENTS AND METHODS: This was a single-center, randomized control trial. A total of 78 patients diagnosed by selective coronary angiography (CAG) participated in this study. Patients' demographics, medical history, medications, and results of laboratory testing were collected. The index of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were obtained by CAG and single-photon emission computed tomography (SPECT) separately. Fasting blood samples were obtained on the morning following the admission day. Concentrations of several molecules of inflammation, endothelial function, and coronary microvascular function were measured by ELISA. Patients were followed-up two months after discharge and fasting blood samples were also acquired. RESULTS: All patients were randomly divided into 2 groups: GXSC, 38 (48.7%), and control, 40 (51.3%). The intergroup comparison revealed no significant differences with respect to all baseline variables. As for inflammation biomarkers, proinflammatory NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin (IL)-1 were significantly decreased in GXSC compared with the control group (0.71±0.08 vs. 1.04±0.07, p<0.01 and 7.16±0.59 vs. 10.93±1.04, p<0.01). Anti-inflammatory adropin was increased in the GXSC group (7.75±0.59 vs. 5.71±0.68, p=0.03). As for indexes of endothelial function, the concentrations of syndecan (SDC) 1, SDC4 and heparan sulphates (HS) were significantly downregulated in 2 months GXSC treatment (3.31±0.28 vs. 4.85±0.43, p<0.01, 3.79±0.56 vs. 5.69±0.68, p=0.03 and 21.31±2.79 vs. 35.18±4.11 p<0.01). In addition, the level of SIRTUIN 1 (SIRT1), which is a vascular protective protein, was upregulated in GXSC group (5.63±0.30 vs. 4.22±0.37, p<0.01). As for molecules of coronary microvascular function, endocan, soluble urokinase plasminogen activator receptor (suPAR), and growth differentiation factor (GDF)-15 were significantly decreased consistently in GXSC compared with the control group (0.09±0.01 vs. 0.19±0.03, p<0.01, 4.44±0.40 vs. 5.73±0.40, p=0.03 and 2.08±0.17 vs. 2.69±0.18, p=0.02). CONCLUSIONS: In conclusion, GXSC could improve CMD by inhibiting inflammation and restoring endothelial function. GXSC might be an effective drug in CAD patients without obstructive epicardial coronary arteries but suffering from angina.

Retraction Note: Effect of atorvastatin on pulmonary arterial hypertension in rats through PI3K/AKT signaling pathway.

The article "Effect of atorvastatin on pulmonary arterial hypertension in rats through PI3K/AKT signaling pathway", by Y.-Y. Wang, X.-D. Cheng, H. Jiang, published in Eur Rev Med Pharmacol Sci 2019; 23 (23): 10549-10556-DOI: 10.26355/eurrev_201912_19696-PMID: 31841211 has been retracted by the Authors. After publication, issues were raised on PubPeer about the reliability of the published results, in particular, of Figures 2 and 3. The authors stated that the article presents some inaccuracies as the data cannot be repeated by further research. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19696.

Preparation of drug-loaded chitosan microspheres repair materials.

OBJECTIVE: With the development of society and the progress of science and technology, microspheres, as a new polymer material, have been applied to all aspects of human beings. Microspheres can play a huge role in food safety, electronic technology, sewage treatment, biomedicine, etc., and are non-toxic or harmless. There are three main types of substrates for the preparation of microspheres: natural polymers, semi-synthetic polymer materials, and synthetic polymer materials. MATERIALS AND METHODS: In this study, the inorganic material kaolin was modified by the emulsification-crosslinking method with chitosan and composite microspheres with large interlayer spacing were prepared, which were characterized by Fourier Transform Ioncyclotron Resonancel (FTIR) analysis and Scanning Electron Microscope (SEM). The prepared kaolin/chitosan microspheres were then placed in different amounts of aspirin and the optimal dose was investigated by encapsulation efficiency and drug loading rate. The drug release rate of 0.5 h, 1 h, 1.5 h, 2 h, 4 h, 6 h, and 12 h was then determined by simulating the human colon to determine the performance of the sustained-release drug. RESULTS: The experimental results showed that after the prepared composite microspheres were loaded with aspirin drug, we got the optimal dosage of 0.1 g by discussing the encapsulation efficiency and drug loading rate of the drug-loaded microspheres, and the encapsulation efficiency reached 80.80%, while the drug loading rate was 24.40%, the drug release capacity reached about 83% in about 12 hours. CONCLUSIONS: The research shows that the kaolin/chitosan drug-loaded microspheres prepared by the emulsification and cross-linking method are excellent drug-loading materials.

Relationship between body mass index and pulse pressure in a non-diabetic population: evidence from a multicenter, cross-sectional study.

OBJECTIVE: Growing evidence shows that pulse pressure (PP) is a strong risk factor for cardiovascular disease and is closely associated with cardiovascular events, strokes, and mortality. However, currently, data on the relationship between body mass index (BMI) and PP are still limited. SUBJECTS AND METHODS: Here, a cross-sectional study was conducted based on 211,809 non-diabetic adults in 11 cities in China from 2010 to 2016. Raw data were obtained from a public database (www.datadryad.org). According to the BMI level, they are classified into "underweight", "normal", "overweight", and "obesity" groups. Two groups of continuous variables were measured by the Mann-Whitney test, while the differences between multiple groups were tested by Kruskal-Wallis' One-Way ANOVA and Dunn's test. Besides, multiple linear regression analyses were performed to assess the linear relationship between BMI and PP. In addition, multivariate logistic regression was carried out to further confirm the relationship between different BMI levels and the prevalence of high PP. RESULTS: In the total population, BMI was linearly positively related to PP regardless of gender and age, but it was not observed in the elevated blood pressure group. Multiple linear regression analysis showed that after fully adjusting for the maximum covariates, compared to the normal group, PP in the overall population decreased by 2.19 mmHg in the underweight group and increased by 1.426 and 2.919 mmHg in the overweight and obese groups, respectively. Similar results were observed in men, women, age <60 years, and normotensive groups. However, there was no significantly linear relationship between BMI and PP at the age of ≥60 years and elevated blood pressure groups. Besides, from multiple logistic regression analysis, the similar results were obtained, with no obvious association between BMI and high PP prevalence in those aged ≥60 years or with elevated blood pressure. CONCLUSIONS: PP increased with rising BMI in the overall population. However, stratified analysis demonstrated no significant association between BMI and PP in individuals aged over 60 years or with elevated blood pressure.

Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

Using real-time sound touch elastography to monitor changes in transplant kidney elasticity.

AIM: To use sound touch elastography (STE) to assess the changes of renal cortex among different complications following renal transplantation. MATERIALS AND METHODS: A total of 31 patients with renal dysfunction after renal transplantation underwent an ultrasound-guided biopsy for pathological examination with conventional and STE ultrasound. The maximum elastic modulus (Emax) was determined, and the biopsy specimen was evaluated for evidence of significant differences among four different complications: drug-induced renal damage, acute rejection, chronic allograft nephropathy (CAN), and BK virus (BKV) nephropathy. Receiver operator characteristics were used to compare the diagnostic efficacy of STE ultrasound according to the pathological results. RESULTS: The quantitative index Emax of the STE technique was statistically significant among the four different complications (p<0.05). The distribution of the magnitude of Emax in the renal cortex was BKV nephropathy > CAN > acute rejection > drug induced renal damage. The renal cortex Emax was statistically different for the severity of renal fibrosis and tubular atrophy (p<0.05). CONCLUSION: Each of the four different complications of transplantation influenced the Emax of the renal cortex differently. Emax can be used to assess the severity of renal fibrosis and tubular atrophy.

A common variant rs2272804 in the 5'UTR of RIBC2 inhibits downstream gene expression by creating an upstream open reading frame.

OBJECTIVE: The RIB43A domain with coiled-coils 2 (RIBC2) encodes an uncharacterized vertebrate protein exhibiting similarity with Chlamydomonas protofilament ribbon proteins, required for ciliary motility. To date, no functional variants capable of triggering a change in the expression of RIBC2 have been reported. PATIENTS AND METHODS: The genotypes of rs2272804 in 30 individuals were identified with Sanger sequencing to estimate allele frequencies. Dual-Luciferase and mutagenesis assays were carried out to investigate the impact of rs2272804 on transcriptional and translational levels. The microarray data of 7 types of cancer were obtained from the Gene Expression Omnibus (GEO) to explore the role of rs2272804 in those diseases. RESULTS: In this study, we identified a common variant in the 5'UTR of RIBC2, rs2272804, which can create an upstream open reading frame (uORF) in the 5'UTR significantly inhibiting the expression of its host gene. Using Dual-Luciferase constructs, we found that this variant leads to an 85% reduction in translational efficiency, but only a 20% decrease was observed at the transcriptional level. In terms of population studies, mRNA levels of RIBC2 varied according to their rs2272804 genotypes. The "A" allele homozygotes, which created a uORF, showed the lowest transcriptional levels while the transcriptional activity of the "C" allele homozygotes without an uORF was the highest, consistent with the in-vitro studies. Furthermore, we explored its role in 7 types of cancer and identified RIBC2 as a significantly differentially expressed gene (DEG) in breast cancer (BRCA), ovarian serous cystadenocarcinoma (OV), and kidney renal clear cell carcinoma (KIRC). Finally, we showed that the overexpression of RIBC2 enhanced the expression of TRIM37 and down-regulated TRAF2. TRIM37 is a member of the tripartite motif (TRIM) family involved in developmental patterning and oncogenesis while TRAF2 is associated with the signal transduction from members of the TNF receptor superfamily. CONCLUSIONS: Our reports identified a common variant that exerts a dramatic impact on expression efficiency and provides further functional insight into RIBC2.

Long non-coding RNA FTX alleviates hypoxia/reoxygenation-induced cardiomyocyte injury via miR-410-3p/Fmr1 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the roles and underlying mechanisms of five prime to Xist (FTX) in myocardial I/R injury using cardiomyocyte hypoxia/reoxygenation (H/R) model. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to determine the expression of FTX, microRNA-410-3p (miR-410-3p) and fragile X mental retardation 1 (Fmr1) mRNA. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis were employed to evaluate cell proliferation and apoptosis, respectively. Western blot assay was conducted to examine the protein levels of apoptosis-associated factors and Fmr1. Specific kits were used to detect the levels of oxidative stress-associated factors. Dual-luciferase reporter assay was performed to verify the association between miR-410-3p and FTX or Fmr1. RESULTS: FTX was reduced in myocardial I/R injury patients' serum and H/R-stimulated H9c2 cells. FTX overexpression relieved cell damage caused by H/R treatment through inducing cell proliferation and repressing cell apoptosis and oxidative stress in H9c2 cells. FTX was a sponge for miR-410-3p and the impact of FTX overexpression on H/R-induced cell injury was abolished by miR-410-3p elevation in H9c2 cells. Fmr1 was identified as a target of miR-410-3p and Fmr1 knockdown reversed the effect on H/R-induced cell damage mediated by miR-410-3p inhibition in H9c2 cells. Moreover, FTX positively regulated Fmr1 expression through sponging miR-410-3p in H9c2 cells. CONCLUSIONS: FTX regulated H/R-induced cardiomyocyte damage by upregulating Fmr1 via sponging miR-410-3p.

The prognostic role of FZD6 in esophageal squamous cell carcinoma patients.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC. METHODS: In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown. RESULTS: The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001). CONCLUSION: CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.

Survival and functional outcomes of patients who underwent facial-submental artery island flap reconstruction after oral cavity or HPV-negative oropharyngeal squamous cell carcinoma ablation.

The purpose of this study was to evaluate the outcomes of survival and functional outcome of patients with Oral cavity squamous cell carcinoma (OCSCC) and HPV-negative oropharyngeal squamous cell carcinoma (HPV-negative OPSCC) using FSAIF reconstruction of the defects. The 275 patients were divided into OCSCC and HPV-negative OPSCC group were treated with surgery and oral cavity and oropharynx reconstruction with the FSAIF. The skin paddles in the OCSCC and OPSCC groups were 3×9 to 5×14cm and 3×8 to 5×15cm, respectively. The original primary tumor site was the oral cavity in 203 patients and the oropharynx in 72. No significant differences TNM or clinical stage, skin paddle of the flap, rate of flap failure, or local complications were observed between the OCSCC and HPV-negative OPSCC groups. Ten flap failures occurred, yielding a success rate of 96.4%. There are not differences of survival and speech function of patients with OCSCC and HPV--negative OPSCC using FSAIFs reconstruction of the defects following cancer ablation, but there are differences of the swallowing function. This flap is suitable for reconstructing the defect in the oral cavity or oropharynx.

Combination of biomechanical evaluation and accurate placement of dental implants: a new concept of virtual surgery in maxillary and mandibular functional reconstruction.

Biomechanics are crucial for bony regeneration and survival of implants in functional maxillary and mandibular reconstructions. However, we know of no study that has included an analysis of biomechanics to guide the optimal position of a fibular graft in virtual surgery. This study was designed to evaluate the combination of biomechanics and accurate placement of implants for virtual surgery in reconstruction of the jaw using fibular grafts. Thirty-one patients had maxillary or mandibular reconstruction with vascularised fibular grafts and the immediate placement of dental implants. Virtual studies were made preoperatively to evaluate the biomechanics and to assess the position of the fibular grafts with minimal distribution of stress. All operations proceeded accurately and with no complications with a mean (range) of 14 (6-20) months' follow-up. According to the individual biomechanical evaluations, the optimal position for the fibular graft is probably the middle of the mandibular body or below the bottom of the maxillary sinus. The combination of biomechanical evaluation and accurate placement of dental implants is a new concept that could achieve good biomechanical positioning of fibular grafts in the jaw and a desirable level of accuracy for functional reconstruction.

Effect of atorvastatin on pulmonary arterial hypertension in rats through PI3K/AKT signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of atorvastatin on pulmonary arterial hypertension (PAH) in rats and to observe its specific regulatory mechanism through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/AKT) signaling pathway. MATERIALS AND METHODS: The model of PAH was successfully established in rats via hypoxia feeding. All rats were divided into three groups, including Control group (n=15), PAH model group (Model group, n=15) and atorvastatin treatment group (Ator group, n=15). Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide (NO) were detected via enzyme-linked immunosorbent assay (ELISA). Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined as well. Meanwhile, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining. Furthermore, the apoptosis level of lung tissues in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. In addition, the expression levels of PI3K/AKT signaling pathway and apoptotic genes in lung tissues were detected via quantitative Polymerase Chain Reaction (qPCR). RESULTS: In Model group, the levels of TNF-α and IL-6 increased significantly, while the level of NO decreased. Both RVSP and RVHI in Model group were significantly higher than those of Control group and Ator group (p<0.05). The results of HE staining revealed that Model group showed significantly severe lung tissue injury (p<0.05). According to the results of TUNEL staining, the number of apoptotic cells in lung tissues in Model group was significantly smaller than that of Ator group (p<0.05). Meanwhile, the expression level of cysteinyl aspartate-specific proteinase-3 (Caspase-3) in Model group was markedly lower than that of Ator group (p<0.05). However, the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was markedly higher than that of Ator group (p<0.05). In Ator group, the expression levels of PI3K and AKT in lung tissues were remarkably higher than those of Model group (p<0.05). All the above results indicated that atorvastatin could effectively up-regulate the expressions of PI3K and AKT (p<0.05). CONCLUSIONS: Atorvastatin regulates the symptoms of PAH in rats through activating the PI3K/AKT signaling pathway.

The up-regulated lncRNA DLX6-AS1 in colorectal cancer promotes cell proliferation, invasion and migration via modulating PI3K/AKT/mTOR pathway.

OBJECTIVE: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths around the world. Recently, using the high-throughput techniques, long non-coding RNAs (lncRNAs) have been shown to play an important role in CRC progression. In the present study, we aimed to determine lncRNA DLX6 Antisense RNA 1 (DLX6-AS1) in CRC tissues and cell lines and to investigate the molecular mechanisms of DLX6-AS1 in CRC progression. PATIENTS AND METHODS: Quantitative real-time PCR was performed to detect gene expression; cell counting kit-8, colony formation, cell invasion, and migration assays were performed to determine cell proliferation, invasion, and migration, respectively; caspase-3 activity assay kit was used to detect caspase-3 activity; in vivo tumor growth was evaluated in a nude mice xenograft model. RESULTS: DLX6-AS1 was up-regulated in 60 CRC tissues when compared to normal adjacent colorectal tissues, and high expression of DLX6-AS1 was correlated with advanced T stage and distant metastasis in CRC patients. The up-regulation of DLX6-AS1 was further confirmed in CRC cell lines. The gain-of-function assays showed that DLX6-AS1 overexpression promoted HCT116 cell proliferation, invasion, and migration, but inhibited cell apoptosis; while the loss-of-function assays showed that DLX6-AS1 knockdown exerted the opposite effects in SW480 cells. In vivo studies revealed that DLX6-AS1 knockdown suppressed tumor growth in the nude mice xenograft model. In addition, DLX6-AS1 overexpression caused an increase in the phosphorylated phosphoinositide 3-kinase (p-PI3K), p-AKT and p-mammalian target of rapamycin (mTOR) protein levels, and DLX6-AS1 knockdown had the opposite effects. Blockade of PI3K/AKT/mTOR signalling pathway by using mTOR inhibitor partially abolished the enhanced effects of DLX6-AS1 overexpression on CRC cell proliferation and metastasis. CONCLUSIONS: In summary, our data indicated that DLX6-AS1 promoted CRC cell proliferation, invasion, and migration but inhibited cell apoptosis via targeting PI3K/AKT/mTOR signalling pathway, suggesting the key role of DLX6-AS1 in CRC progression.

Nodal mitigates cerebral ischemia-reperfusion injury via inhibiting oxidative stress and inflammation.

OBJECTIVE: Nodal is a member of the transforming growth factor ß (TGF-ß) family, which induces the activation of the cytoplasmic Smad2 and Smad3, both of which play a neuroprotective role against cerebral ischemia-reperfusion (I/R) injury. However, the  role of Nodal in cerebral I/R is unclear. Thus, the aim of the present study was to shed light on the function of Nodal in cerebral I/R injury. MATERIALS AND METHODS: Cerebral I/R injury was induced in the Sprague Dawley (SD) rats by middle cerebral artery occlusion (MCAO) and reperfusion and in murine hippocampal neuronal cells (HT22) by oxygen-glucose deprivation/reperfusion (OGD/R) stimulation. The lentivirus vectors (Nodal overexpressing lentivirus vector [OE-Nodal] and the short hair RNA of Nodal [sh-Nodal]) were used to upregulate and downregulate Nodal in SD rats or cells. RESULTS: Nodal expression increased in the cerebral I/R models and reached a peak after 12 h of reperfusion. OE-Nodal administration to the cerebral I/R rats significantly reduced the cerebral infarction volume and inhibited the brain cell apoptosis. It also increased the level of superoxide dismutase (SOD), an antioxidant enzyme, and decreased the levels of the lipid peroxides (malondialdehyde [MDA] and lactate dehydrogenase [LDH]), in addition to those of the proinflammatory factors. Consistently, the upregulation of Nodal in HT22 by OGD/R significantly increased the SOD level and decreased the levels of MDA, LDH, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α). CONCLUSIONS: This study revealed that Nodal exerted a protective role during cerebral I/R by inhibiting excessive oxidative stress and inflammation.

Utilizing size-based thresholds of stiffness gradient to reclassify BI-RADS category 3-4b lesions increases diagnostic performance.

AIM: To investigate the role of utilizing size-based thresholds of stiffness gradient in diagnosing solid breast lesions and optimizing original Breast Imaging-Reporting And Data System (BI-RADS) classifications. MATERIALS AND METHODS: Two-hundred and twenty-seven consecutive women underwent shear-wave elastography (SWE) before ultrasound-guided biopsy, and 234 solid breast lesions categorized as BI-RADS 3-5 were analysed. Receiver operating characteristic curve analysis was performed based on histopathology. Diagnostic performance among SWE, BI-RADS, and their combination were compared. RESULTS: The stiffness gradient correlated with the standard deviation of elasticity (SD, r=0.90), and with Tozaki's pattern classification (r=0.64). The area under the receiver operating characteristic curves (AUC) for stiffness gradient (0.939) outperformed SD (0.897) or colour pattern (0.852). Due to significant association with lesion size (r=0.394, p<0.001), stiffness gradient's size-based thresholds (lesions >15 mm: 82.5 kPa; lesions ≤15 mm: 51.1 kPa) were established to reclassify BI-RADS 3-4b lesions. Upgrading category 3 lesions (over the corresponding cut-off value, 3 to 4a) and downgrading categories 4a-4b lesions (less than or equal to the corresponding cut-off value, 4b to 4a, 4a to 3), yielded significant improvement in specificity (90.28% versus 77.78%, p<0.001) and AUC (0.948 versus 0.926, p=0.035) than BI-RADS alone. No significant loss emerged in the sensitivity (88.89% versus 91.11%, p=0.500). CONCLUSION: Stiffness gradient exhibited better discriminatory ability than SD or four-colour pattern classification in determining solid breast lesions and applying its size-specific thresholds to categorize BI-RADS 3-4b lesions could improve diagnostic performance.

Augmented reality for temporomandibular joint arthrocentesis: a cadaver study.

Temporomandibular joint (TMJ) arthroscopic procedures require the identification of a skin puncture point. The puncture point is conventionally estimated using the surface anatomy of the canthal-tragus line. However, the conventional puncture technique has been reported to fail at the first attempt in 18% of cases. We propose an augmented reality (AR) system-based method to identify the puncture point on the skin. A three-dimensional virtual model was reconstructed from computed tomography images of a cadaver head, and its rendered image was superimposed on the cadaver head before skin puncture. The skin puncture point was marked on the skin under the guidance of the AR system. The TMJ was punctured through the mark and the endoscope was introduced through the puncture point. The outcome of the procedure was classified as successful or unsuccessful based on the visualization of the TMJ. The system was applied on the left and right sides of three cadaver heads. Puncture with the AR method was successful in all six cases. This study presents a system to provide AR visualization during TMJ arthrocentesis to increase the precision of skin puncture. However, a comparative study of the AR method with the conventional method is required to evaluate its advantages.

Evaluation of the effects of right ventricular pressure load on left ventricular myocardial mechanics in patients with chronic obstructive pulmonary disease by ultrasound speckle tracking imaging.

OBJECTIVE: This paper aims to evaluate the effects of right ventricular pressure load on left ventricular myocardial mechanics in patients with chronic obstructive pulmonary disease (COPD) by ultrasound speckle tracking imaging. PATIENTS AND METHODS: 119 patients with COPD and pulmonary hypertension (PH) were selected from December 2016 to March 2018 in Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University. 42 healthy subjects were selected as control group. According to the pulmonary arterial systolic pressure (PASP), 41 patients were classified into mild group, 47 in moderate group, and 31 cases in severe group. Echocardiography and STI were used to measure the indexes. RESULTS: Compared with those in control group, EI and E/e of moderate group and severe group increased significantly (p<0.001). Compared with those in control group, parameters in moderate and severe groups significantly decreased (p<0.001), including early diastolic mitral annular velocity/late peak blood flow velocity (E/A), left ventricular end diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), PASP and left ventricular end-diastolic diameter (LVEDD), stroke volume (SV), left ventricular end-systolic diameter (LVESD), cardiac output (CO), peak rotation angle and peak time of in the basal and apical segments. Compared with those in control group, parameters in moderate group significantly decreased (p<0.001), including left ventricular strain parameters segmental systolic peak longitudinal strain (LS), circumferential strain (CS), and radial strain (RS). Compared with those in control group, parameters in mild group significantly decreased (p<0.001), including peak rotation angle of basal segment and apical segment of the left ventricle. Compared with those in moderate group, peak rotation angle and peak time of the whole basal segment and apical segment of severe group gradually decreased (p<0.001). CONCLUSIONS: Left ventricular whole peak rotation angle can be used to sensitively evaluate the change of left ventricular myocardial mechanics function in PH patients, and can reflect changes of left ventricular myocardial mechanics function in patients with COPD when mild PH occurs.

Combinatory effect of mesenchymal stromal cells transplantation and quercetin after spinal cord injury in rat.

OBJECTIVE: To investigate the synergistic effects of quercetin (Qu) administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following spinal cord injury (SCI). MATERIALS AND METHODS: HUMSCs were isolated, cultured and certificated via flow cytometry. Sixty Sprague-Dawley (SD) female rats were used and SCI models were made. All rats were divided into five experimental groups: culture medium treated group (n=28); HUSMCs + quercetin-treated group (n = 28); HUMSCs treated group (n=28); quercetin-treated group (n = 28); sham group (n = 20). Basso, Beattie, and Bresnahan (BBB) were used to assess neurological function recovery. Axons at the injury epicenter of the injury were checked by immunohistochemical analysis. Cystic cavity was measured and rat cytokine Luminex custom 8-plex kits (for interleukin (IL)-4, IL-1ß, IL-6, IL-10, interferon (IFN)-γ, tumor necrosis factor (TNF)-ß1) were checked. RESULTS: The combination treatment with Qu and delayed transplantation of HUMSCs after rat SCI improved neurological functional recovery, increased axonal preservation, promoted macrophage polarization, decreased the size of the cystic cavity, reduced the proinflammatory cytokines, including IL-1ß and IL-6. Also, it increased anti-inflammatory cytokines, including IL-4, IL-10, and transforming growth factor (TGF)-ß1. CONCLUSIONS: We showed that HUMSCs transplantation in combination with Qu was a potential strategy for reducing secondary damage and promoting functional recovery following SCI.

Whole-exome sequencing identifies a homozygous donor splice-site mutation in STAG3 that causes primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is the depletion or loss of normal ovarian function, which cause infertility in women before the age of 40 years. Two homozygous germline truncation mutations in STAG3 gene had been reported to causes POI in consanguineous families. Here, we aimed to identify the genetic cause of POI in 2 affected sisters manifested with primary amenorrhea and partial development of secondary sexual characters with normal range of height of a consanguineous Han Chinese family. Whole-exome and Sanger sequencing identified a homozygous donor splice-site mutation (NM_012447.2: c.1573+5G>A) in the STAG3 gene. RT-PCR revealed that the mutation causes loss of wild-type donor splice-site which leads to aberrant splicing of STAG3 mRNA and consecutive formation of STAG3 alternative transcript (p.Leu490Thrfs*10) . This is the first report of splice-site mutation of STAG3 gene causes POI in 2 Han Chinese patients.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. METHODS: Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. CONCLUSIONS: This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.