Projection Test for Mean Vector in High Dimensions.

This paper studies the projection test for high-dimensional mean vectors via optimal projection. The idea of projection test is to project high-dimensional data onto a space of low dimension such that traditional methods can be applied. We first propose a new estimation for the optimal projection direction by solving a constrained and regularized quadratic programming. Then two tests are constructed using the estimated optimal projection direction. The first one is based on a data-splitting procedure, which achieves an exact t-test under normality assumption. To mitigate the power loss due to data-splitting, we further propose an online framework, which iteratively updates the estimation of projection direction when new observations arrive. We show that this online-style projection test asymptotically converges to the standard normal distribution. Various simulation studies as well as a real data example show that the proposed online-style projection test retains the type I error rate well and is more powerful than other existing tests.

Development and validation of potential phenotypes of serum electrolyte disturbances in critically ill patients and a Web-based application.

BACKGROUND: Electrolyte disturbances are highly heterogeneous and severely affect the prognosis of critically ill patients. Our study was to determine whether data-driven phenotypes of seven electrolytes have prognostic relevance in critically ill patients. METHODS: We extracted patient information from three large independent public databases, and clustered the electrolyte distribution of ICU patients based on the extreme value, median value and coefficient of variation of electrolytes. Three plausible clinical phenotypes were calculated using K-means clustering algorithm as the basic clustering method. MIMIC-IV was considered a training set, and two others have been designated as verification set. The robustness of the model was then validated from different angles, providing dynamic and interactive visual charts for more detailed characterization of phenotypes. RESULTS: 15,340, 12,445 and 2147 ICU patients with electrolyte records during early ICU stay in MIMIC-IV, eICU-CRD and AmsterdamUMCdb were enrolled. After clustering, three reasonable and interpretable phenotypes are defined as α, ß and γ according to the order of clusters. The α and γ phenotype, with significant differences in electrolyte distribution and clinical variables, higher 28-day mortality and longer length of ICU stay (p < 0.001), was further demonstrated by robustness analysis. The α phenotype has significant kidney injury, while the ß phenotype has the best prognosis. In addition, the assignment methods of the three phenotypes were developed into a web-based tool for further verification and application. CONCLUSIONS: Three different clinical phenotypes were identified that correlated with electrolyte distribution and clinical outcomes. Further validation and characterization of these phenotypes is warranted.

A nomogram for predicting echocardiogram prescription in outpatients: an analysis of the NAMCS database.

Background and objective: Cardiovascular disease is the leading cause of morbidity and mortality globally. Echocardiography is a commonly used method for assessing the condition of patients with cardiovascular disease. However, little is known about the population characteristics of patients who are recommended for echocardiographic examinations. Methods: The National Ambulatory Medical Care Survey was a cross-sectional survey previously undertaken in the USA. In this study, publicly accessible data from the National Ambulatory Medical Care Survey database (for 2007-2016 and 2018-2019; data for 2017 was not published) were utilized to create a nomogram based on significant risk predictors. The study was performed in accordance with the relevant guidelines and regulations stipulated in the National Ambulatory Medical Care Survey database. Patients were randomly assigned to one of two groups: training cohort or validation cohort. The latter was used to assess the reliability of the prediction nomogram. Decision curve analysis was performed to evaluate the net benefit. Propensity score matching analysis was used to evaluate the relevance of echocardiography to clinical decision-making. Results: A total of 217,178 outpatients were enrolled. Multivariable logistic regression analysis demonstrated that hypertension, hyperlipidemia, coronary artery disease/ischemic heart disease/history of myocardial infarction, congestive heart failure, major reason for visit, metropolitan statistical area, cerebrovascular disease/history of stroke or transient ischemic attack, previously assessed, insurance, referred, diagnosis, and reason for visit were all predictors of echocardiogram prescription in outpatients. The reliability of the predictive nomogram was confirmed in the validation cohort. After propensity score matching, there was a significant difference in new cardiovascular agent prescriptions between the echocardiogram and no echocardiogram groups (P < 0.01). Conclusion: In this cohort study, a nomogram based on the characteristics of outpatients was developed to predict the possibility of prescribing echocardiography. The echocardiogram group was more likely to be prescribed new cardiovascular agents. These findings may contribute to providing information about the gap between actual utilizations and guidelines and the actual outpatient practice, as well as meeting the needs of outpatients.

An Early Indicator in Evaluating Cardiac Dysfunction Related to Premature Ventricular Complexes: Cardiorespiratory Capacity.

Cardiac dysfunction induced by premature ventricular complexes (PVCs) is relatively controversial and challenging to detect in the early stage. In this observational study, we retrospectively analyzed the cardiopulmonary exercise test (CPET) data of 94 patients with frequent premature ventricular beats (47 males, 49.83 ± 13.63 years) and 98 participants (55 males, 50.84 ± 9.41 years) whose age and gender were matched with the patient with PVCs. The baseline information and routine echocardiography detection were recorded on admission. PVCs were diagnosed by 24 h Holter monitoring, and cardiorespiratory capacity was assessed using peak oxygen uptake (V'O2peak), anaerobic threshold (AT), and other CPET parameters with an individualized bicycle ramp protocol according to the predicted workload and exercise situation of each participant. There were no statistically significant differences in most baseline characteristics between the two groups. Indicators that reflect cardiopulmonary capacity, such as V'O2peak, AT, and ΔO2 pulse/Δwork rate(ΔV'O2/ΔWR), were all significantly lower in the PVC group (p = 0.031, 0.021, and 0.013, respectively) despite normal and nondiscriminatory left ventricular ejection fractions between the two groups. However, there was no statistically significant difference among subgroups based on the frequency of PVCs, which was <10,000 beats/24 h, 10,000-20,000 beats/24 h, and >20,000 beats/24 h. The cardiorespiratory capacity was lower in patients with frequent PVCs, indicating that CPET could detect early signs of impaired cardiac function induced by PVCs.

Low lymphocyte to high-density lipoprotein ratio predicts mortality in sepsis patients.

Background: The lymphocyte-to-high-density lipoprotein (HDL) ratio (LHR) is associated with both inflammation and immunity, and may have the potential to predict the prognosis of sepsis. Our study aimed to evaluate the relationship between LHR and sepsis-related mortality. Methods: We collected data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.2) database by targeting patients who met the Sepsis-3 criteria and recorded the absolute values of lymphocytes and HDL after admission. We then used restricted cubic splines based on logistic regression to simulate the relationship between the LHR and 90-day mortality. Subsequently, the hazardous threshold was derived based on the mortality curve, and further evaluations were performed using different methods and data sources for hazardous threshold. Results: We ultimately included 1027 eligible patients from the MIMIC-IV database and described the nonlinear relationship between LHR and 90-day mortality. Based on the curve, an LHR of ≤ 0.6 indicated harmful threshold, and the odds ratio for mortality was 1.74 (P=0.001). The outperforming hazard was particularly marked in patients with chronic lung disease and remained consistent after adjusting for baseline data and validating multiple data sources. Conclusions: The LHR has prognostic value in patients with sepsis, and an LHR ≤ 0.6 is a deleterious load that increases mortality.

Early persistent exposure to high CVP is associated with increased mortality and AKI in septic shock: A retrospective study.

PURPOSE: This study's objective was to investigate the association between exposure to different intensities of central venous pressure (CVP) over time in patients with septic shock with 28-day mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We obtained data from the AmsterdamUMCdb, which includes data on patients ≥18 years old with septic shock undergoing CVP monitoring. The primary outcome was mortality by day 28. Piecewise exponential additive mixed models were used to estimate the strength of the association over time. RESULTS: 9668 patients were included in the study. They exhibited 8.2% overall mortality at 28 days and 41.1% AKI incidence. Daily time-weighted average CVP was strongly associated with increased mortality at 28 days, primarily within 24 h of ICU admission. The mortality rate of patients was lowest when the CVP was 6-12 cmH2O. When the time of high CVP (TWA-CVP >12 cmH2O) exposure within the first 24 h was >5 h, the risk of death increased by 2.69-fold. Additionally, patients exposed to high CVP had a significantly increased risk of developing AKI. CONCLUSIONS: The optimal CVP range for patients with septic shock within 24 h of ICU admission is 6-12 cmH2O. Mortality increased when patients were exposed to high CVP for >5 h.

Effects of perioperative exercise on cardiorespiratory endurance in children with congenital heart disease in plateau areas after surgical repair.

We aimed to explore the effects of perioperative exercise on cardiorespiratory endurance in children with congenital heart disease (CHD) in plateau areas after surgical repair. Fifty children with CHD in the plateau admitted to our hospital were randomly divided into the exercise and control groups. The exercise group received a perioperative exercise intervention beginning within 24 h postoperatively, while the control group received routine nursing and treatment alone. To assess the 6 min walk distance (6MWD) at baseline and at end of intervention, children participated in a 6-min walk test before cardiac repair and at 1 week after general ward transfer. A subset of children in the study underwent the cardiopulmonary exercise test pre-operatively. The 6MWD of children with CHD at baseline was positively correlated with the peak oxygen uptake pre-operatively. No significant difference was reported in the preoperative baseline data of both groups. The 6MWD of the exercise group was significantly higher than that of the control group. Early exercise therapy after cardiac repair could significantly improve the cardiorespiratory endurance and exercise capacity of children with CHD in plateau areas.

MCCC2 is a novel mediator between mitochondria and telomere and functions as an oncogene in colorectal cancer.

BACKGROUND: The mitochondrial gene MCCC2, a subunit of the heterodimer of 3-methylcrotonyl-CoA carboxylase, plays a pivotal role in catabolism of leucine and isovaleric acid. The molecular mechanisms and prognostic value still need to be explored in the context of specific cancers, including colorectal cancer (CRC). METHODS: In vitro and in vivo cell-based assays were performed to explore the role of MCCC2 in CRC cell proliferation, invasion, and migration. Mitochondrial morphology, membrane potential, intracellular reactive oxygen species (ROS), telomerase activity, and telomere length were examined and analyzed accordingly. Protein complex formation was detected by co-immunoprecipitation (CO-IP). Mitochondrial morphology was observed by transmission electron microscopy (TEM). The Cancer Genome Atlas (TCGA) CRC cohort analysis, qRT-PCR, and immunohistochemistry (IHC) were used to examine the MCCC2 expression level. The association between MCCC2 expression and various clinical characteristics was analyzed by chi-square tests. CRC patients' overall survival (OS) was analyzed by Kaplan-Meier analysis. RESULTS: Ectopic overexpression of MCCC2 promoted cell proliferation, invasion, and migration, while MCCC2 knockdown (KD) or knockout (KO) inhibited cell proliferation, invasion, and migration. MCCC2 KD or KO resulted in reduced mitochondria numbers, but did not affect the gross ATP production in the cells. Mitochondrial fusion markers MFN1, MFN2, and OPA1 were all upregulated in MCCC2 KD or KO cells, which is in line with a phenomenon of more prominent mitochondrial fusion. Interestingly, telomere lengths of MCCC2 KD or KO cells were reduced more than control cells. Furthermore, we found that MCCC2 could specifically form a complex with telomere binding protein TRF2, and MCCC2 KD or KO did not affect the expression or activity of telomerase reverse transcriptase (TERT). Finally, MCCC2 expression was heightened in CRC, and patients with higher MCCC2 expression had favorable prognosis. CONCLUSIONS: Together, we identified MCCC2 as a novel mediator between mitochondria and telomeres, and provided an additional biomarker for CRC stratification.

Delta like Non-Canonical Notch Ligand 2 inhibits chondrogenic differentiation and cell proliferation of bone marrow mesenchymal stem cells through the Notch1 signaling pathway.

Bone marrow mesenchymal stem cells (BMSCs) is the candidate for the treatment of cartilage defects because of their directional induction potential and natural anti-inflammatory properties. As one of the non-canonical receptors of Notch1, Delta Like Non-Canonical Notch Ligand 2 (DLK2) involves in stem cells' adipogenesis and chondrogenic differentiation. However, the specific regulatory mechanism of DLK2 in the chondrogenic differentiation of BMSCs is still unclear. In this study, we found that the expression of DLK2 was reduced and the expression of Col2a1, Col10a1, Acan, Sox9, and Notch1 was raised in the process of BMSCs chondrogenic differentiation. However, the expression of Col2a1, Col10a1, Acan, and Sox9 reduced significantly, and the signal factor Notch1 and the chondrogenic differentiation capacity of BMSCs turned down in the DLK2 overexpression group. Furthermore, the expression of Col2a1, Col10a1, Acan, and Sox9 significantly enhanced, Notch1 expression was also increased, and the chondrogenic differentiation capacity of BMSCs turned up in the DLK2 suppression group. Concurrently, the proliferation of BMSCs was weakened after overexpression of DLK2, and there was no significant change in cell migration. However, the proliferation and migration of BMSCs were significantly enhanced after the inhibition of DLK2 expression. Therefore, these results suggest that DLK2 negatively regulates chondrogenic differentiation and cell proliferation in BMSCs by inhibiting the Notch1 signaling pathway.

[Corrigendum] A potential therapeutic effect of CYP2C8 overexpression on anti­TNF­α activity.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the cell migration assay experiments shown in Fig. 5 on p. 731, the 'TNF­α' data panels in Fig. 5A and C appeared to be matching, where experiments performed under different conditions were intended to have been displayed. After having re­examined their original data, the authors have realized that the data files were mislabelled, although they were able to retrieve the correct data for Fig. 5C (where the error occurred). The revised version of Fig. 5, containing the correct data for the TNF­α experiment shown in Fig. 5C, is shown on the next page. Note that the error made during the assembly of this figure did not affect the overall conclusions reported in the paper. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this. They also apologize to the readership for any inconvenience caused. [International Journal of Molecular Medicine 34: 725­732, 2014; DOI: 10.3892/ijmm.2014.1844].

Feature Screening for Interval-Valued Response with Application to Study Association between Posted Salary and Required Skills.

It is important to quantify the differences in returns to skills using the online job advertisements data, which have attracted great interest in both labor economics and statistics fields. In this paper, we study the relationship between the posted salary and the job requirements in online labor markets. There are two challenges to deal with. First, the posted salary is always presented in an interval-valued form, for example, 5k-10k yuan per month. Simply taking the mid-point or the lower bound as the alternative for salary may result in biased estimators. Second, the number of the potential skill words as predictors generated from the job advertisements by word segmentation is very large and many of them may not contribute to the salary. To this end, we propose a new feature screening method, Absolute Distribution Difference Sure Independence Screening (ADD-SIS), to select important skill words for the interval-valued response. The marginal utility for feature screening is based on the difference of estimated distribution functions via nonparametric maximum likelihood estimation, which sufficiently uses the interval information. It is model-free and robust to outliers. Numerical simulations show that the new method using the interval information is more efficient to select important predictors than the methods only based on the single points of the intervals. In the real data application, we study the text data of job advertisements for data scientists and data analysts in a major China's online job posting website, and explore the important skill words for the salary. We find that the skill words like optimization, long short-term memory (LSTM), convolutional neural networks (CNN), collaborative filtering, are positively correlated with the salary while the words like Excel, Office, data collection, may negatively contribute to the salary.

CircSFMBT2-OA alleviates chondrocyte apoptosis and extracellular matrix degradation through repressing NF-κB/NLRP3 inflammasome activation.

Background: Intra-articular inflammation and cartilage degradation are the major pathological characteristics of osteoarthritis (OA). Mounting studies have revealed that circular RNAs (circRNAs) act as an important regulatory role in inflammatory diseases and are frequently dys-expressed in OA cartilage tissues. Objective: Here, a dys-regulated cicrRNA (has_circ_0017636, termed circSFMBT2-OA) was identified, and its role in regulating lipopolysaccharide (LPS)-induced chondrocyte injury was next investigated. Methods: CHON-001 chondrocytes were treated with LPS, and then the levels of circSFMBT2-OA, cartilage-related genes, and pro-inflammatory cytokines were measured using quantitative real-time PCR (qRT-PCR) and Western blot analysis. CHON-001 cell viability, proliferation, and apoptosis were assayed using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EDU), and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, respectively. Results: CircSFMBT2-OA level was significantly down-regulated in OA cartilage tissues and LPS-treated CHON-001 cells. Functionally, circSFMBT2-OA overexpression accelerated cell proliferation, and suppressed cell apoptosis, pro-inflammatory cytokines production, matrix-degrading enzymes expression, and ECM degradation in CHON-001 cells. Inversely, circSFMBT2-OA depletion decreased cell viability and increased matrix-degrading enzymes expression and ECM degradation. Mechanistically, circSFMBT2-OA inhibited LPS-induced NF-κB/NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome activation in CHON-001 cells. Consequently, NLRP3 activator reversed the effect of circSFMBT2-OA on repressing LPS-induced CHON-001 cell injury. Conclusion: These data reveal a vital effect of a novel circSFMBT2-OA on repressing OA progression and provide a promising target to treat OA.

Comparison of accuracy for hip-knee-ankle (HKA) angle by X-ray and knee motion analysis system and the relationships between HKA and gait posture.

BACKGROUND: The lower limb mechanical axis was used to assess the severity of knee osteoarthritis (KOA) with varus/valgus deformity and the accuracy of targeted lower limb alignment correction after operation by conventional X-rays. There are lots of parameters to assess the gait in elder patients such as velocity, stride length, step width and swing/stance ratio by knee joint movement analysis system. However, the correlation between the lower limb mechanical axis and gait parameters is not clear. This study is aimed at obtaining the accuracy of the lower limb mechanical axis by the knee joint movement analysis system and the correlation between the lower limb mechanical axis and gait parameters. METHODS: We analysed 3D knee kinematics during ground gait of 99 patients with KOA and 80 patients 6 months after the operations with the vivo infrared navigation 3D portable knee joint movement analysis system (Opti-Knee®, Innomotion Inc, Shanghai, China). The HKA (Hip-Knee-Ankle) value was calculated and compared to X-ray findings. RESULTS: HKA absolute variation after the operation was 0.83 ± 3.76°, which is lower than that before the operation (5.41 ± 6.20°, p = 0.001) and also lower than the entire cohort (3.36 ± 5.72). Throughout the cohort, a significant correlation with low coefficients (r = -0.19, p = 0.01) between HKA value and anterior-posterior displacement was found. In comparing the HKA values measured on the full-length alignment radiographs and 3D knee joint movement analysis system (Opti-Knee), there was a significant correlation with moderate to high coefficients (r = 0.784 to 0.976). The linear correlation analysis showed that there was a significant correlation between the values of HKA measured by X-ray and movement analysis system (R2 = 0.90, p < 0.01). CONCLUSIONS: Data with equivalent results as HKA, the 6DOF of the knee and ground gait data could be provided by infrared navigation based 3D portable knee joint movement analysis system comparing with the conventional X-rays. There is no significant effect of HKA on the kinematics of the partial knee joint.

A Transparent Additive-Free Fibrous Facial Mask for Skin Moisturizing.

Most sheet facial masks for skincare are made of nonwovens and loaded with liquid active ingredients, which are usually opaque and require additives for long-term preservation. Herein, a Transparent Additive-Free Fibrous (TAFF) facial mask is reported for skin moisturizing. The TAFF facial mask consists of a bilayer fibrous membrane. The inner layer is fabricated by electrospinning functional components of gelatin (GE) and hyaluronic acid (HA) into a solid fibrous membrane to get rid of additives, the outer layer is an ultrathin PA6 fibrous membrane that is highly transparent, especially after absorbing water. The results indicate that the GE-HA membrane can quickly absorb water and become a transparent hydrogel film. By employing the hydrophobic PA6 membrane as the outer layer, directional water transport is achieved, which enables TAFF facial mask with excellent skin moisturizing effect. The skin moisture content is up to 84% ± 7% after placing the TAFF facial mask on the skin for 10 min. In addition, the relative transparency of the TAFF facial mask on the skin reaches 97.0% ± 1.9% when ultrathin PA6 membrane is used as the outer layer. The design of the transparent additive-free facial mask may serve as a guideline for developing new functional facial masks.

Multifunctional Extracellular Matrix Hydrogel with Self-Healing Properties and Promoting Angiogenesis as an Immunoregulation Platform for Diabetic Wound Healing.

Treating chronic wounds is a global challenge. In diabetes mellitus cases, long-time and excess inflammatory responses at the injury site may delay the healing of intractable wounds. Macrophage polarization (M1/M2 types) can be closely associated with inflammatory factor generation during wound healing. Quercetin (QCT) is an efficient agent against oxidation and fibrosis that promotes wound healing. It can also inhibit inflammatory responses by regulating M1-to-M2 macrophage polarization. However, its limited solubility, low bioavailability, and hydrophobicity are the main issues restricting its applicability in wound healing. The small intestinal submucosa (SIS) has also been widely studied for treating acute/chronic wounds. It is also being extensively researched as a suitable carrier for tissue regeneration. As an extracellular matrix, SIS can support angiogenesis, cell migration, and proliferation, offering growth factors involved in tissue formation signaling and assisting wound healing. We developed a series of promising biosafe novel diabetic wound repair hydrogel wound dressings with several effects, including self-healing properties, water absorption, and immunomodulatory effects. A full-thickness wound diabetic rat model was constructed for in vivo assessment of QCT@SIS hydrogel, in which hydrogels achieved a markedly increased wound repair rate. Their effect was determined by the promotion of the wound healing process, the thickness of granulation tissue, vascularization, and macrophage polarization during wound healing. At the same time, we injected the hydrogel subcutaneously into healthy rats to perform histological analyses of sections of the heart, spleen, liver, kidney, and lung. We then tested the biochemical index levels in serum to determine the biological safety of the QCT@SIS hydrogel. In this study, the developed SIS showed convergence of biological, mechanical, and wound-healing capabilities. Here, we focused on constructing a self-healing, water-absorbable, immunomodulatory, and biocompatible hydrogel as a synergistic treatment paradigm for diabetic wounds by gelling the SIS and loading QCT for slow drug release.

One-stop interventional procedure for bicuspid aortic stenosis in a patient with coexisting aortic coarctation: a case report.

Introduction: Coarctation of the aorta (CoA) is usually diagnosed and corrected early in life. Most untreated patients with CoA usually die before 50 years of age. Adult patients with concomitant CoA and severe bicuspid aortic stenosis are relatively rare and present complex management challenges without standard guidelines. Case summary: A 63-year-old female patient with uncontrolled hypertension was admitted due to chest pain and dyspnea upon exertion (NYHA grades III). Echocardiogram showed a severely calcified and stenotic bicuspid aortic valve (BAV). A severe stenotic calcified eccentric aortic coarctation 20 mm distal to the left subclavian artery (LSA) was discovered by computed tomography (CT) angiography. Following consultation with the cardiac team and patient willingness, we performed a one-stop interventional procedure to repair both defects. First, a cheatham-platinum (CP) stent was implanted via the right femoral access, immediately distal to the LSA. Due to the markedly twisted and angled descending aortic arch, we chose to perform transcatheter aortic valve replacement (TAVR) via the left common carotid artery. The patient was discharged and followed up for 1 year without symptoms. Discussion: Although surgery is still the main treatment for these diseases, it is not suitable for high-risk surgical patient. Transcatheter intervention for patients with severe aortic stenosis complicated with CoA simultaneously is rarely reported. The success of this procedure depends on the patient's vascular condition, the skills of the heart team, and the availability of the technical platform. Conclusion: Our case report demonstrates the feasibility and efficacy of a one-stop interventional procedure in an adult patient with concurrent severely calcified BAV and CoA via two different vascular approaches. Transcatheter intervention, in contrast to traditional surgical approaches or two-stop interventional procedures, as a minimally invasive and novel method, offers a wider range of therapeutic methods for such diseases.

Regulation of Chondrocyte Differentiation by miR-455-3p Secreted by Bone Marrow Stem Cells through Phosphatase and Tensin Homolog Deleted on Chromosome Ten/Phosphoinositide 3-Kinase-Protein Kinase B.

The effects of the regulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) by microribonucleic acid- (miR-) 455-3p on bone marrow stem cells' (BMSCs') chondrogenic development were examined based on the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathway. The alterations in miR-455-3p and PTEN were identified using osteoarthritis (OA) and healthy chondrocytes. Rats raised on the SD diet had their BMSCs isolated for chondrocyte-induced differentiation (blank group), transfected miR-455-3p mimic (mimic group), and inhibitor (inhibitor group). Besides, cell proliferation, alizarin red mineralization staining, and the activity of alkaline phosphatase (ALP) were detected. Real-time fluorescent quantitation polymerase chain reaction (PCR) and Western blot were utilized to detect Runx2, OPN, OSX, COL2A1 mRNA, and the difference between PI3K and AKT. Dual-luciferase reporter (DLR) genes were selected to analyze the target relationship of miR-455-3p to PTEN. It was demonstrated that miR-455-3p in OA was downregulated, while PTEN was upregulated (P < 0.05) in comparison to healthy chondrocytes (P < 0.05). Versus those in the blank group, alizarin red mineralization staining and the activity of ALP increased; RUNX, OPN, OSX, COL2A1 mRNA, p-PI3K, and p-AKT were elevated in the mimic group (P < 0.05). Versus those in the blank and mimic groups, alizarin red mineralization staining and the activity of ALP reduced; RUNX, OPN, OSX, COL2A1 mRNA, p-PI3K, and p-AKT were downregulated in the inhibitor group (P < 0.05). miR-455-3p could target PTEN to inhibit its expression, thus activating the PI3K/AKT signal pathway and promoting BMSCs chondrocyte-induced differentiation. The research results provided reference for the occurrence of OA and the study on therapeutic target.

Evaluation of RT-LAMP Assay for Rapid Detection of SARS-CoV-2.

OBJECTIVE: To evaluate the accuracy of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in community or primary-care settings. METHOD: We systematically searched the Web of Science, Embase, PubMed, and Cochrane Library databases. We conducted quality evaluation using ReviewManager software (version 5.0). We then used MetaDisc software (version 1.4) and Stata software (version 12.0) to build forest plots, along with a Deeks funnel plot and a bivariate boxplot for analysis. RESULT: Overall, the sensitivity, specificity, and diagnostic odds ratio were 0.79, 0.97, and 328.18, respectively. The sensitivity for the subgroup with RNA extraction appeared to be higher, at 0.88 (0.86-0.90), compared to the subgroup without RNA extraction, at 0.50 (0.45-0.55), with no significant difference in specificity. CONCLUSION: RT-LAMP assay exhibited high specificity regarding current SARS-CoV-2 infection. However, its overall sensitivity was relatively moderate. Extracting RNA was found to be beneficial in improving sensitivity.

A New Coronavirus Estimation Global Score for Predicting Mortality During Hospitalization in Patients with COVID-19.

Objective: Coronavirus disease 2019 (COVID-19) exists as a pandemic. Mortality during hospitalization is multifactorial, and there is urgent need for a risk stratification model to predict in-hospital death among COVID-19 patients. Here we aimed to construct a risk score system for early identification of COVID-19 patients at high probability of dying during in-hospital treatment. Methods: In this retrospective analysis, a total of 821 confirmed COVID-19 patients from 3 centers were assigned to developmental (n = 411, between January 14, 2020 and February 11, 2020) and validation (n = 410, between February 14, 2020 and March 13, 2020) groups. Based on demographic, symptomatic, and laboratory variables, a new Coronavirus estimation global (CORE-G) score for prediction of in-hospital death was established from the developmental group, and its performance was then evaluated in the validation group. Results: The CORE-G score consisted of 18 variables (5 demographics, 2 symptoms, and 11 laboratory measurements) with a sum of 69.5 points. Goodness-of-fit tests indicated that the model performed well in the developmental group (H = 3.210, P = 0.880), and it was well validated in the validation group (H = 6.948, P = 0.542). The areas under the receiver operating characteristic curves were 0.955 in the developmental group (sensitivity, 94.1%; specificity, 83.4%) and 0.937 in the validation group (sensitivity, 87.2%; specificity, 84.2%). The mortality rate was not significantly different between the developmental (n = 85,20.7%) and validation (n = 94, 22.9%, P = 0.608) groups. Conclusions: The CORE-G score provides an estimate of the risk of in-hospital death. This is the first step toward the clinical use of the CORE-G score for predicting outcome in COVID-19 patients.

Establishment of a meta-analysis based novel aortic dissection mouse model.

Aortic dissection (AD) is a life-threatening disease and the detailed mechanism remains unclear. Thus, proper animal models are urgently required to better understand its pathogenesis. Our current study aims to establish a reliable, time and cost-effective mouse AD model. To conduct the meta-analysis, we searched PubMed for related studies up to 2021 and statistical analysis was conducted using Review Manager 5.4. For the animal experiment, 6-week-old male ApoE-/- mice were given ß-aminopropionitrile (BAPN) at a concentration of 1 g/L for 3 weeks before being infused with saline, 1000 ng/kg/min or 2500 ng/kg/min angiotensin II (AngII) via osmotic mini pumps for 2 or 4 weeks. To determine the presence of AD, we performed B-ultrasonography, hematoxylin and eosin (H&E) staining, and van Gieson staining. The result of the meta-analysis showed that the use of BAPN and more than 2000 ng/kg/min AngII can increase the rate of AD formation, whereas administrating Ang II for more than 28 days has no significant effect on the rate of AD formation when compared with the less than 14 days group. In the present study, mice treated with BAPN combined with 2500 ng/kg/min AngII for 2 weeks (12/20) had a significantly higher AD formation rate than mice treated with BAPN combined with 1000 ng/kg/min Ang II for 4 weeks (2/10), and had a similar model formation rate compared with the mice treated withß-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks (6/10). There were 3 mice (3/10) and 6 mice (6/20) who died in the group treated with ß-aminopropionitrile combined with 2500 ng/kg/min AngII for 4 weeks and 2 weeks respectively, and only one mouse (1/10) died in the group treated with ß-aminopropionitrile combined with 1000 ng/kg/min AngII for 4 weeks. In 6-week-old male ApoE-/- mice that received with 1 g/L BAPN in the drinking water for 3 weeks along with 2500 ng/kg/min AngII infusion via osmotic mini pumps for 2 weeks, the highest model formation rate and relative lower cumulative mortality were noted.