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To investigate clinical outcomes of countertraction method in treating irreducible subcoracoid dislocation of shoulder joint combined with Hill-Sacks injury.A total of 56 patients with irreducible subcoracoid dislocation of the shoulder joint combined with Hill-Sacks injury admitted from December 2013 to June 2020 were retrospectively analyzed. Under the anesthesia of shoulder joint cavity injection, the reduction was performed by using anti-traction method (experimental group) and traditional Hippocrates method (control group), 28 cases in each group. There were 11 males and 17 females in experimental group, with an average age of (61.95±19.32) years old, 9 cases on the left side, and 19 cases on the right side. Twelve males and 16 females in control group, with an average age of (63.13±12.75) years old, 11 cases on the left side, 17 cases on the right side. The curative effects between two groups were evaluated before and after operation, including the success rate of reduction, the duration of reduction, the distance from successful reduction to injury, complications and functional rehabilitation(Constant score of shoulder joint).The success rates of reduction in experimental group and control group were 92.86%(26/28) and 67.86% (19/28), respectively, and the difference was statistically significant (For patients with irreducible subcoracoid dislocation of the shoulder joint with Hill-Sacks injury, the countertraction method under anesthesia of the shoulder joint cavity achieved a higher success rate and few complications.

STORMS checklist forEffects of investigational moisturizers on the skin barrier and microbiome after exposure to environmental aggressors: a randomized clinical trial and ex vivo analysis

The abnormal proliferation of vascular smooth muscle cells (VSMCs) is crucial in the atherosclerosis. Although long noncoding RNAs (lncRNAs) are implicated in a variety of diseases, their roles in activation of VSMCs proliferation and vascular disorder diseases are not well understood. In addition, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) was reported to participate in lncRNAs-mediated function. Herein, we propose to investigate the role of lncRNA AC105942.1 and hnRNPA2/B1 in pathological VSMCs proliferation and the possible mechanisms in vitro. We have identified that lncRNA AC105942.1 was downregulated and hnRNPA2/B1 was upregulated in atherosclerotic plaques compared with normal artery tissues. Enhanced lncRNA AC105942.1 could noticeably inhibit Ang II-induced VSMCs proliferation. Further investigation suggested that lncRNA AC105942.1 could downregulate the expression of hnRNPA2/B1 and then regulate the level of CDK4 and p27. Taken together, our study indicated that lncRNA AC105942.1 downregulated hnRNPA2B1 to protect against the atherosclerosis by suppressing VSMCs proliferation. LncRNA AC105942.1 and hnRNPA2/B1 could represent potential therapeutic and diagnostic targets to atherosclerosis-related diseases.

Objectives To investigate the cross‐section shape of the femoral neck isthmus (FNI) in three‐dimensional reconstruction model of the femoral neck. Methods From December 2009 to December 2012, computed tomography (CT) data of bilateral hip joint from 200 consecutive patients (137 males and 63 females, 69.41 ± 9.21 years old, ranged from 50–85 years old) who underwent surgical treatments for proximal femoral fracture were retrospectively reviewed. The 3D model of the proximal femur was reconstructed, and the “inertia axis” method, which was applied to measure the long and short axes of the cross‐section of the FNI, was established. The cross‐sectional area and perimeter were calculated by a formula using the length of the long and short axes and then compared with the actual measured values by the software. Correlation between the descriptive parameters of the FNI cross‐section (area, perimeter, and eccentricity) and patients' demographics (age, height, and weight) was analyzed. Stepwise linear regression analysis was used to determine the main relevant factors. Results The ICC results showed excellent data reproducibility ranged from 0.989 to 0.996. There was no significant difference in the cross‐sectional area of the FNI between the actual measured values and the predicted values using the formula (732.83 ± 126.74 mm2 vs 731.62 ± 128.15 mm2, P = 0.322). The perimeter using the two methods showed narrow while significant difference (97.86 ± 8.60 mm vs 92.84 ± 8.65 mm, P, The morphological features of the cross‐section of the femoral neck, especially the femoral neck isthmus (FNI), are of great significance for the spatial configuration of the screws used in the internal fixation of femoral neck fractures. This study utilizes the three‐dimensional model of the proximal femur to segment the FNI plane. We found that the actual measured data of FNI cross‐section was in line with the values calculated using elliptical equations, thus proving that FNI cross‐section was approximately elliptical.

Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Recent studies have indicated that UDP-glucose pyrophosphorylase 2(UGP2) is implicated in cell proliferation and survival. Here we investigated the anti-apoptosis and anti-atherogenic effect of UGP2 in vitro and in vivo.Here, we explored the effects and mechanisms of UGP2 on apoptosis in endothelial cells by flow cytometer and Western blot analyses. And we engineered ldlr−/−ugp2+/− double-deficient mice to evaluated the apoptosis levels in atherosclerotic lesion. A microarray analysis showed that the expression of UGP2 was reduced in human atherosclerotic plaques. In vitro experiments revealed that TP53 interacted with the promotor region of the UGP2 gene, which upregulated UGP2 expression. Augmentation of UGP2 expression downregulated ROS levels, the expressions of Cleaved caspase-3 and apoptosis levels in endothelial cells, and this inhibitory effects of UGP2 on cell apoptosis could be significantly abolished by H2O2. In vivo experiments using ldlr−/−ugp2+/− mice fed a Western high-fat diet demonstrated that UGP2 deficiency promoted atherosclerosis, and increased the levels of ROS, expressions of Cleaved caspase-3 and apoptosis cells in atherosclerotic lesions. Thus, our results provide evidence for UGP2 as a novel target gene of TP53 contributes to anti-apoptosis effect linking to ROS homeostasis differ from canonical pathway, and we suggested that UGP2 could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.

Atherosclerosis is an immune inflammatory disease and a major cause of mortality and morbidity worldwide. It is generally considered that a number of potent proinflammatory cytokines have a great influence on its pathogenesis, including IL-1β, IL-6, TNF-α, and NF-κB. A growing amount of empirical evidence indicates that the mechanism of cardiac dysfunction caused by lipopolysaccharide (LPS) is the activation of inflammation, but the exact mechanism in atherosclerosis is still unclear. Previous studies have shown that interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) participates in inflammation, but the effects and possible mechanism of action of IFIT1 on proinflammatory response remain largely unexplained. We found that LPS induced upregulation of IFIT1 expression in a time- and concentration-dependent manner in human umbilical vein endothelial cells (HUVECs). Overexpression of IFIT1 significantly upregulated LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. IFIT1-siRNA treatment dramatically decreased LPS-induced expression of IL-1β, IL-6, TNF-α, and NF-κB in HUVECs. The above results show that LPS induces expression of IL-1β, IL-6, TNF-α, and NF-κB through upregulating IFIT1 expression in HUVECs, and suggested that IFIT1 could act as potential therapeutic target to ameliorate atherosclerosis-related diseases.

Background and aims Many clinical trials have demonstrated that statins convey protective effects against atherosclerosis independent of cholesterol-lowering capacities. Other evidence indicates that pyroptosis, a type of programmed cell death, is likely involved in atherosclerosis, but the effects and mechanisms of statins on pyroptosis must be further revealed. Methods Here, we explored the effects and mechanisms of atorvastatin on pyroptosis in human vascular endothelial cells by quantitative real-time polymerase chain reaction and Western blot analyses. Results Atorvastatin upregulated long non-coding RNA (lncRNA) NEXN-AS1 and the expression of NEXN at both the mRNA and protein levels in a concentration- and time-dependent manner. Atorvastatin inhibited pyroptosis by decreasing the expression levels of the canonical inflammasome pathway biomarkers NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 at both the mRNA and protein levels. The promotion effects of atorvastatin on NEXN-AS1 and NEXN expression could be significantly abolished by knockdown of lncRNA NEXN-AS1 or NEXN, and its inhibitory effects on pyroptosis were also markedly offset by knock-down of lncRNA NEXN-AS1 or interference of NEXN. Conclusions These results demonstrated that atorvastatin regulated pyroptosis via the lncRNA NEXN-AS1-NEXN pathway, which provides a new insight into the mechanism of how atorvastatin promotes non-lipid-lower effects against the development of atherosclerosis and gives new directions on how to reverse atherosclerosis.

Closed reduction and internal fixation with three cannulated compression screws is a common method for treating femoral neck fractures in young and middle-aged patients. Protocols including the inverted triangle configuration and dispersion of the screws still needed further supports. The purpose of this study was to explore a novel oblique triangle configuration (OTC) of three screws in fixing femoral neck fractures based on the morphology of the femoral neck isthmus (FNI). The computer-aided design modules were used to explore the ideal spatial configuration with largest triangle by three parallel screws. A univariate evaluation model was established based on the oval-like cross-section of the FNI. When the three screws were positioned by the OTC, Inverted Equilateral Triangle Configuration (IETC), and the Maximum Area Inverted Isosceles Triangle Configuration (MA-IITC) respectively, the proportion of area and circumference in the cross-section of FNI and the changing trend of proportion were compared under various torsion angles, eccentricity, and cross-sectional area of FNI. The area and circumference ratios of the parallel screws using the OTC method were significantly higher than in the IETC and MA-IITC groups. In the univariate evaluation model, the OTC area ratio and circumference ratio remained stable under the different femoral neck torsion angles, FNI cross-sectional area, and eccentricity. The OTC method provided an ideal spatial configuration for the FNA fixation with the largest area using three parallel screws. The position of the posterior screw was also away from the metaphyseal artery, potentially reducing the possibility of vascular injury and screw penetrating.

To investigate the genetic mutation types and ethnic distribution characteristics of thalassemia in Guiyang.The population underwent physical examination, antenatal examination and pre-pregnancy examination in our hospital from January 2019 to November 2019 was selected, and the thalassemia gene was detected by RDB-PCR.Among the 4 572 samples, 346 were positive , and the total carrying rate was 7.57%. The carrying rate of α-thalassaemia gene was 5.42% (248 cases), while β-thalassemia was 1.99% (91 cases), and α+β-compound thalassemia was 0.15% (7 cases). α-thalassaemia genotype with the lack of right side -αThe gene types of thalassemia in Guiyang are complex and varied. The -α贵阳地区地中海贫血基因突变类型及民族分布特点分析.了解贵阳地区α、β- 地中海贫血基因突变类型和民族分布特点。.对2019年1- 11月在贵州中医药大学第一附属医院进行体检、产检、孕前检查的贵阳地区人群，采用RDB-PCR方法检测α、β-地中海贫血基因。.4 572例送检样本中，共检出阳性样本346例，地中海贫血基因总携带率为7.57%，其中α-地中海贫血基因携带率为5.42%（248例），β-地中海贫血基因携带率为1.99%（91例），α+β复合型地中海贫血基因携带率为0.15%（7例）。α-地中海贫血基因型以右侧缺失-α贵阳地区地中海贫血基因类型复杂多样，α-地中海贫血以-α

Limited evidence was found in the associations of volatile organic compound (VOC) exposure with bone health indicators. This study aimed to explore the associations of individual and combined metabolites of VOCs (mVOCs) in urine, a representative of the internal exposure level of VOCs, with bone mineral density (BMD), osteoporosis (OP) and fracture, and potential mediators. Data of the National Health Examination and Nutrition Survey 2005-2006 and 2013-2014 was used. Multiple linear and logistic regression modeling were performed to analyze the associations of individual mVOC with bone health indicators. The least absolute shrinkage and selection operator (LASSO) regression was adopted to select mVOCs that were more relevant to bone health indicators for further weight quantile sum (WQS) analysis used for analyzing the associations between multiple VOC co-exposure and bone health indicators. Mediation analysis was used to identify potential mediators. Seventeen mVOC members with detection rate of50% in urine of all 3478 participants aged ≥20 years (1829 females) were involved. Levels of most mVOCs were higher in women than men. Eight mVOCs were negatively associated with BMDs, and two and four mVOCs were positively associated with OP and fracture risks, respectively. WQS regression revealed decreased femoral neck BMD (β = -0.010 g/cm

BackgroundFew studies have explored the association between water intake and mortality risk, and the findings were inconsistent.ObjectiveThis study aimed to explore the water intake–mortality association, utilizing the data from the National Health and Nutrition Examination Survey (NHANES) and the 2015 public-linked mortality files released by the National Center for Health Statistics.MethodsWe used the diet- and mortality-linked data of a total of 35,463 adults (17,234 men) aged ≥20 years in the NHANESs 1999–2014 to perform a prospective study. The multivariate-adjusted Cox proportional hazards model was used to explore the associations of the amount of water intake (expressed by total water, plain water, beverage, and food water) and water intake proportion (expressed by the percentage of each kind of water) with mortality risks due to all causes, malignant neoplasms/cancer, and heart disease. The restricted cubic spline plots were adopted to clarify the dose–response relationships among them.ResultsWith a median of 88 months (interquartile range: 49–136 months) follow-up, a total of 4,915 all-cause deaths occurred, including 1,073 and 861 deaths from malignant neoplasms/cancer and heart disease, respectively. The amount of water intake in either type was negatively associated with all-cause mortality risk. Additionally, the negative linear dose–response relationships of water intake and all-cause mortality risk were found for all types of water except for food water, which followed a non-linear pattern. Similarly, compared to the lowest quartile (beverage water intake: ConclusionOur findings demonstrated that higher water intake is associated with lower mortality risks among the United States population.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype.Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

A pilot randomized controlled trial (RCT) was conducted in mainland China to examine the feasibility, acceptability, and preliminary effects of parent-administered pediatric tuina on attention deficit hyperactivity disorder (ADHD) symptoms in preschool children. An embedded process evaluation was performed to explore barriers and facilitators in the implementation, identify additional questions, and refine the study design for a future fully powered study.The process evaluation comprises the following parts: (a) self-reported questionnaires on parents (n = 43), traditional Chinese medicine (TCM) practitioners (n = 2), outcome assessor (n = 1), and research assistant (n = 1); (b) parent logbook on parent-administered pediatric tuina (n = 32); and (c) focus group interview sessions (n = 15). Accomplishment of the self-report questionnaires was voluntary for all participants and compulsory for research personnel and TCM practitioners. The parent logbook on the intervention was filled out by all participants in the intervention group. Participants of focus group interviews were selected via purposive sampling, and data were analyzed with template analysis. Qualitative findings were summarized in tables, while the mean was calculated to reflect the quantitative findings.Perceived benefits, acceptability of parents and children, and professional support from the research team facilitated the implementation of the intervention. Meanwhile, the TCM pattern identification using online mode may limit the accuracy and lead to parents doubting the precision of the TCM pattern. This limitation was regarded as a major barrier. Parents perceived improvements in terms of children's appetite, sleep quality, and parent-child relationship. Participants were generally satisfied with the settings of parent-administered pediatric tuina and showed satisfactory adherence to the implementation.Implementation of parent-administered pediatric tuina intervention is feasible and acceptable. The intervention can be refined by improving the TCM pattern identification procedure and adjusting outcome settings in a fully powered study in the future.

Various multi-drug-resistant microorganisms have appeared while a single antibacterial agent is increasingly no longer adequate for dealing with these resistant microorganisms. Herein, commercially purchased 50 nm-average-diameter silver nanoparticles (AgNPs) and Lactobacillus buchneri-isolated surface-layer proteins (SLPs) as a capping agent were used to fabricate a hybrid antibacterial agent (SLP-AgNPs) with enhanced antibacterial activity, and the possible synergistic antibacterial mechanism was explored. Characterization results revealed that SLP-AgNPs were uniformly surrounded by protein corona provided from SLP, and the formulations were mainly mediated by the electrostatic interactions and hydrogen bonding, which was evidenced by the results of Fourier transform infrared spectroscopy. According to the antibacterial tests, the minimum inhibitory concentration of SLP-AgNPs against Salmonella enterica (0.010 mg/mL) and Staphylococcus aureus (0.005 mg/mL) was 5-10 times lower than that of bare AgNPs, and while SLP-AgNPs showed a higher antibiofilm activity. Furthermore, bacterial cells exposed to SLP-AgNPs exhibited higher cell membrane permeability and stronger inhibition of respiratory-chain dehydrogenase activity, resulting in more severe cell death compared with bare AgNPs. The synergistic effect of SLP on AgNPs was probably carried out by enhanced function of adhesion to bacteria and antibacterial ability of SLP and SLP's supramolecular lattice structure on the sustained release of silver ion.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population. Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations. Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype. Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

Existing epidemiological studies explored the associations of circulating vitamins and mortality focusing on individual vitamin effects, and controversial findings were obtained. The joint effects of multiple vitamin co-exposure are worth studying. The study aimed to elucidate the associations of circulating vitamins and the joint effects of these vitamins' co-exposure with all-cause and cause-specific mortality risks.We prospectively evaluated the associations of the concentrations of six kinds of vitamins (A, D, E, C, B12 and B9) in serum with risks for all-cause and cause-specific mortalities among U.S. adults. Mortality status and cause of death were determined by NHANES-linked public available files dated up to 31 December 2015. An unsupervised K-means clustering method was used to cluster the participants into several vitamin co-exposure patterns. The Cox proportional hazards model was used for statistical analysis.A total of 1404 deaths occurred during a median of 10.9 years follow-up among 8295 participants. In multivariable adjustment, increasing levels of vitamin D were associated with reduced all-cause and cause-specific mortality risks. A J-shaped nonlinear exposure-response relationship was observed between all studied vitamins (except for vitamin D) and all-cause mortality risk. Four co-exposure patterns were generated based on the studied vitamins, as follows: low-level exposure (cluster 1), vitamin A/D exposure (cluster 2), water-soluble vitamin exposure (cluster 3) and high-level exposure (cluster 4). Compared with those in cluster 1, participants in cluster 2 had lower all-cause and cancer mortality risks, with hazard ratios (95% confidence intervals [CIs]) of 0.67 (0.53, 0.85) and 0.45 (0.29, 0.71), respectively.The findings in this study indicated that high circulating vitamin D levels were associated with reduced mortality risk among U.S. adults. Vitamin co-exposure at moderate levels appropriately contributed to low all-cause and cancer mortality risks. Our findings provided a novel perspective for exploring the joint health effects of multivitamin co-exposure. Future investigations are needed to further unravel the underlying mechanisms of possible vitamin interactions.

Background The cross-sectional area of three parallel screws might affect the stability of the internal fixation of femoral neck fractures. The screws fixed in the oblique-triangle configuration (OTC) were assumed to have a larger cross-sectional area, but the biomechanical stability has not yet been validated. In this study, finite element analyses were performed to compare the biomechanical properties of the internal fixation fixed by the OTC and the traditional Inverted Equilateral Triangle Configuration (IETC). Method Pauwels type III fracture was established on the three-dimensional femoral model and three cannulated screws with the OTC and traditional IETC methods were applied. The oblique-triangle configuration with the largest area inscribed the femoral neck isthmus by the three screws was determined, the area and circumference of the cross-section formed by the OTC and IETC model were compared. Stress, strain, and displacement peaks of the two configuration models under different loads were compared. Twelve pairs of nodes on the fracture ends were selected and the displacement of the fracture ends was evaluated through the displacement between these nodes. Results The area and circumference of the cross-section formed by the OTC were larger than those in the IETC model. The degree of stress dispersion around the screw holes in the OTC model was better than that of the IETC, but the stress distribution order of the three screws in the two models was consistent. The maximum stress, strain, displacement, and displacement of the fracture end in the OTC model were smaller than those in the IETC model. The stress, strain, displacement, and fracture end displacement peaks of the two fixed models gradually increase with the increase of loads. Conclusion The oblique-triangle configuration showed superior mechanical properties than the IETC in finite element analyses. This study suggests that when three screws are fixed in parallel method, the larger the cross-sectional area of the screw configuration, the better stability of the internal fixation might be obtained. Furthermore, the biomechanical properties of various spatial configurations and screw holes of the three parallel screws need to be considered before clinical practice.

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011–2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (β = −0.022, 95% CI: −0.036, −0.008) and total BMD (β = −0.015, 95% CI: −0.024, −0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose–response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.

Xiumei Hu,1,* Changmeng Wu,1,* Bo Situ,1,* Peifu Tian,2,* Taixue An,1 Qiang Li,1 Weilun Pan,1 Ruyi Zhang,1 Biao Yang,3 Dehua Sun,1 Yuhai Hu,2 Qian Wang,1,3 Lei Zheng1 1Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 2Department of Medicine Laboratory, Hankou Hospital of Wuhan, Wuhan 430010, People’s Republic of China; 3Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zheng; Qian Wang Email nfyyzhenglei@smu.edu.cn; wangqian@smu.edu.cnObjective: The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now rapidly spreading globally. Serological tests are an important method to assist in the diagnosis of COVID-19, used for epidemiological investigations. In this study, we aimed to investigate the impact of different types of vacuum collection tubes on the detection of SARS-CoV-2 IgM and IgG antibodies, using the colloidal gold immunochromatographic assay (GICA).Patients and Methods: A total of 112 patients with COVID-19 and 200 healthy control subjects with no infection were enrolled in this study. Their serum and plasma were collected into four different types of vacuum blood collection tubes. SARS-CoV-2 IgM and IgG specific antibodies in the plasma and serum were then detected by GICA and chemiluminescence assay (CA), respectively. In addition, the particle sizes of different colloidal gold solutions in the presence of different anticoagulants and coagulants were evaluated by both laser diffraction (Malvern) and confocal laser microscope, respectively.Results: Our results revealed that anticoagulated plasma with EDTA-K2 improved the positive detection rate of SARS-CoV-2 IgM antibodies. Furthermore, our results shown that the detection results by GICA and CA were highly consistent, especially, the results of EDTA-K2 anticoagulated plasma detected by GICA was more consistent with CA results. We confirmed that EDTA-K2 could improve the detection sensitivity of SARS-CoV-2 IgG antibodies by chelating excessive colloidal gold compared with sodium citrate or lithium heparin, these methodologies did not appear to cause false positives. Colloidal gold particles could be chelated and aggregated by EDTA-K2, but not by sodium citrate, lithium heparin and coagulants.Conclusion: GICA is widely used to detect antibodies for the advantages of convenient, fast, low cost, suitable for screening large sample and require minimal equipment. In this study, we found that EDTA-K2 amplified the positive antibody signal by chelating colloidal gold and improved the detection sensitivity of SARS-CoV-2 IgM and IgG antibodies when using the GICA. Therefore, we suggested that EDTA-K2 anticoagulated plasma was more suitable for the detection of SARS-CoV-2 antibodies.Keywords: EDTA-K2, SARS-CoV-2, antibodies, gold immunochromatographic assay; GICA

Highlights • Heating-activation at 56 °C for 30 min does not impair the antibodies of SARS-CoV-2. • Heating-activation would not decrease the diagnostic efficacy of SARS-CoV-2 IgM or IgG antibodies (ELISA-immunoassay). • Sera inactivated by heating should be recommended to minimize the risk of virus contamination of laboratory staff., Background To establish a safe and accurate method for detecting SARS-CoV-2 IgM and IgG, we assessed the impact of sera after heat-inactivation on the SARS-CoV-2 IgM and IgG levels measured by ELISA-immunoassay. Methods The serum samples of 62 patients with COVID-19 and 18 healthy controls were collected in Hankou’s Hospital of Wuhan from February 27 to March 6, 2020. Before and after the samples were inactivated, the levels of IgM and IgG antibodies were measured. Results The indexes of antibodies after inactivated were significantly higher than those in fresh sera, while the positive rates in all participants or in patients with COVID-19 did not change. The positive coincidence rate, negative coincidence rate and total coincidence rate of IgM antibodies before and after inactivation were 100.00% (55/55), 96.00% (24/25) and 98.75% (79/80), respectively (κ = 0.971, P

Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases.

The general features and genomic characteristics of gram-positive Deinococcus sp. D7000 isolated from the hadal region of Mariana Trench Challenger Deep were analyzed in this study. Deinococcus sp. D7000 has a genome consisting of 4,558,742 bp, including one chromosome and nine plasmids. This strain exhibits extracellular protease activity under low temperatures. Among 4328 protein-coding sequences (CDSs), 47 encode serine peptidases. Multiple annotation analysis was used to identify two genes encoding extracellular subtilases. In addition, three types of extracellular secretion transporter systems were found upon pathway construction and analysis. Genome analysis offers insights into the putative pathway of extracellular protease and application prospect of Deinococcus sp. D7000 in enzyme development.

Background The femoral neck torsion angle (FNTA) is an important but often neglected parameter in assessments of the anatomical morphology of the femoral neck, which is often confused with the femoral neck anteversion angle (FNAA) in the current literature. Currently, the measurement methods reported in the literature all adopt the naked eye or two-dimensional (2D) visualization method, and the measurement parameters and details are not clearly defined. The objection of this research was to provide a reliable 3D method for determining the femoral neck axis, to improve the measurement method of the FNTA, and to analyze the anatomical and clinical significance of the results. Methods Computed tomography (CT) data of 200 patients who received a lower extremity CT angiography examination were selected, and the bilateral femurs were reconstructed with three dimensional CT (3D CT). First, the 3D axis of the femoral neck was built. Second, the long axis of the cross section the femoral neck isthmus (FNI) and femoral neck basilar part (FNB) were confirmed by the “inertia axes” method, and the plane consisting of the long axis of the cross-section and the center of the femoral head was defined as the long axial plane. Third, the coronal plane of the proximal femur was determined through the long axis of the proximal femur and the femoral coronal. Finally, the FNTAs (the angles between the long axial planes and the coronal plane of the proximal femur) of FNI and FNB were measured. The size of FNTA was compared between the sexes and sides and different locations, the correlation between the parameters and age, height, and weight were evaluated. Results The difference in FNTA was statistically significant between the isthmus and the basilar part (isthmus 30.58 ± 8.90° vs. basilar part 23.79 ± 3.98°; p < 0.01). Significant difference in the FNTA was observed between the sexes (males 31.99 ± 9.25° vs. females 27.49 ± 7.19°; p < 0.01). The increase in FNTA from the basilar part to the isthmus was 6.79 ± 8.06°, and the male (7.87 ± 8.57°) was greater than the female (4.44 ± 6.23°, p < 0.01). However, no significant difference in the values was observed between sides. Height exerted the greatest effect on the FNTA according to the correlation analysis (r = 0.255, p< 0.001). Conclusions This study found a reliable 3D method for the determination of the femoral neck axis improved the measurement method of the FTNTA and made it more accurate and repeatable. The results provided a methodological basis and theoretical support for the research and development of internal fixation device for femoral neck fracture and the spatial configuration of implants in treatment. And the optimal opening point of the femoral medullary cavity was recommended to locate at the posterior position of the top of the femoral neck cross-section during hip replacement.

Background and aims Long noncoding RNAs (lncRNAs) have recently been implicated in many biological and disease processes, but the exact mechanism of their involvement in atherosclerosis is unclear. The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) is a major contributor to the development of atherosclerotic lesions. This study aimed to investigate the potential effects of lncRNA ZNF800, a previously uncharacterized lncRNA, on VSMC proliferation and migration. Methods The expression of lncRNA ZNF800 in atherosclerotic plaque tissues was detected using reverse transcription–quantitative PCR (RT-qPCR), while the role and mechanism of lncRNA ZNF800 in proliferation and migration of VSMCs were investigated by CCK8 assay, transwell assay, scratch wound assay, RT-qPCR and Western blot. Results We found that lncRNA ZNF800 was significantly more abundant in atherosclerotic plaque tissues, and substantially suppressed the proliferation and migration of VSMCs. LncRNA ZNF800 had no effect on phosphatase and tensin homolog deleted on chromosome 10 (PTEN) mRNA expression but dramatically increased the levels of PTEN protein. Enhanced lncRNA ZNF800 expression inhibited the activity of the AKT/mTOR/HIF-1α signaling pathway, downregulated the expression of vascular endothelial growth factor α (VEGF-α) and matrix metalloproteinase 1 (MMP1), and suppressed VSMC proliferation and migration. These inhibitory effects of lncRNA ZNF800 were abolished by knockdown of PTEN. The inhibitory effects of lncRNA ZNF800 on cell proliferation and migration and the expression of VEGF-α and MMP1 were exacerbated by HIF-1α knockdown in VSMCs. Conclusions These findings demonstrated that lncRNA ZNF800 suppressed VSMC proliferation and migration by interacting with PTEN through a mechanism involving AKT/mTOR/HIF-1α signaling. Therefore, it may play a key atheroprotective role and represent a potential therapeutic target for atherosclerosis-related diseases.

Additional file 2: Figure S1. Phylogenetic tree constructed based on 16S rRNA gene sequences of the degenerate primer amplicon clone. The tree shows the diversity of the 16S rRNA gene clone sequences amplified using degenerate primer 26ABF. This primer was applied in three sediment samples S1, S2 (depth, 15–40 cm). Other 16S rRNA gene reference sequences were retrieved from SILVA_132, NCBI, and GTDB databases. The phylogenetic tree was reconstructed based on 16S rRNA gene sequences derived from the Asgard superphylum via the maximum likelihood method, using MEGA5.0. All 16S rRNA gene sequences are > 1200 bp. The scale bar indicates the number of substitutions per site. The bootstrap support value was set to 1000, and nodes above 0.75 are denoted with black circles.

Background:Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aβ25-35-mediated apoptosis. However, few studies try to understand how Aβ1-42affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level.Methods:Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aβ1-42except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats.Results:We observed that Aβ1-42infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aβ1-42also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aβ1-42could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3β (GSK-3β). Meanwhile, these phenomena could be ameliorated when Tan IIA was used.Conclusion:We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3β signal pathway.

Quercetin, a naturally occurring flavonoid, has been reported to exert antidepressant effects, however, the underlying mechanisms are still uncertain. Recent studies have demonstrated that Forkhead box transcription factor G1 (FoxG1) regulates the process of adult hippocampal neurogenesis (AHN) and exerts neuroprotective effects. In this study, we explored whether quercetin plays an anti-depressant role via regulation of FoxG1 signaling in mice and revealed the potential mechanisms. To explore the antidepressant effects of quercetin, mice were subjected to behavioral tests after a chronic unpredictable mild stress (CUMS) exposure. We found that chronic quercetin treatment (15 mg/kg, 30 mg/kg) obviously restored the weight loss of mice caused by CUMS and alleviated CUMS-induced depression-like behaviors, such as increased sucrose consumption, improved locomotor activity and shorten immobility time. In addition, to clarify the relationship between quercetin and AHN, we detected neurogenesis markers in the dentate gyrus (DG) of the hippocampus. Furthermore, FoxG1-siRNA was employed and then stimulated with quercetin to further investigate the mechanism by which FoxG1 participates in the antidepressant effects of quercetin. Our results indicate that chronic quercetin treatment dramatically increased the number of doublecortin (DCX)-positive and BrdU/NeuN-double positive cells. Besides, the expression levels of FoxG1, p-CREB and Brain-derived neurotrophic factor (BDNF) were also enhanced by quercetin in the DG. Strikingly, quercetin failed to reverse the levels of p-CREB and BDNF after FoxG1-siRNA was performed in SH-SY5Y cells and Neural Progenitor Cells (NPCs). Our results thus far suggest that quercetin might exert antidepressant effects via promotion of AHN by FoxG1/CREB/ BDNF signaling pathway.

Background: Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. Objective: To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. Materials and Methods: A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. Results: A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with ‘fatigue’ and ‘worry’ domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. Conclusions: The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.

To study the characteristics and clinical effect of total hip arthroplasty(THA) for osteoarthritis and (or) avascular necrosis of femoral head after failure of internal fixation of acetabular fracture.From February 2009 to October 2014, 31 patients (31 hips) with hip traumatic osteoarthritis and (or) femoral head avascular necrosis after failure of internal fixation of acetabular fracture were treated with THA including 26 males and 5 females, who injured when the average age of(41±12) years. THA were performed, and the duration ranged from 3 to 132 months with a mean of(20.6±26.9) months secondary to traumatic osteoarthritis and(or) femoral head avascular necrosis. All THA were performed with posterior-lateral approach. The postoperative complications were observed. VAS and Harris hip scores were compared pre-operation and post-operation.Twenty-seven cases were followed up, and the duration ranged from 12 to 80 months with a mean of (43.2±11.7) months. One patient had infection around prosthesis. Aseptic loosening occurred in 1 patient, dislocation of prosthesis in 1 patient. No sciatic nerve injury occurred. Hip function and gaits were obviously improved. To the last follow-up, VAS score was decreased from 7.6±1.2 pre-operatively to 1.2±0.9 post-operatively, while the Harris score was improved from 45.5±13.6 pre-operatively to 88.5±7.8 post-operatively, both differences were statistically significant(Correct dealing with of internal fixation implants, looking out potential infection and reasonable reconstruction of acetabular bone deficiency were the key to the success of THA for osteoarthritis and(or) avascular necrosis of femoral head after failure of internal fixation of acetabular fracture.

Three new triterpenoid saponins, named julibroside J16 (2), julibroside J17 (3), and julibroside J21 (4), each of which possesses an oleanane triterpenoid aglycone of acacic acid, two monoterpenoid acids, and nine sugar moieties, together with one known saponin, julibroside II (1), were isolated from the stem bark of Albizia julibrissin by chromatographic methods. Their structures were established by chemical and spectroscopic means. Saponins 1, 2, and 4 showed inhibitory activities against Bel 7402 human cancer cell line in vitro.

Bowen’s disease, also known as an intraepithelial squamous cell neoplasia, is a carcinoma in situ firstly reported in 1912 by a dermatologist named Bowen from the United States [1]. About 3%~5% of Bowen’s disease might develop into invasive squamous cell carcinomas of mocusa and skin [2]. Surgical resection is preferred because of its low recurrence. Here we reported a rare Bowen’s disease case presented with multiple perianal lesions that were given surgical resection, but relapsed after 2 years.

Two new saponins have been isolated from the stem barks of Albizzia julibrissin Durazz, and their structures identified as 3-O-[beta-D-xylopyranosyl-(1 --2)-beta-D-fucopyranosyl-(1 --6)-beta-D-2-deoxy-2-acetoamidoglucopyranosyl]-21-O-{(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[4-O-((6S)-2-trans-2-hydroxymethyl-6-hydroxy-6-methyl-2,7-octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl}-acacic acid-28-O-beta-D-glucopyranosyl-(1 --3)-[alpha-L-arabinofuranosyl-(1 --4)]-alpha-L-rhamnopyranosyl-(1 --2)-beta-D-glucopyranosyl ester (1) and 3-O-[beta-D-xylopyranosyl-(1 --2)-beta-D-fucopyranosyl-(1 --6)-beta-D-2-deoxy-2-acetoamidoglucopyranosyl]-21-O-{(6S)-2-trans-2-hydroxymethyl-6-methyl-6-O-[3-O-((6S)-2-trans-2-hydroxymethyl-6-hydroxy-6-methyl-2,7-octadienoyl)-beta-D-quinovopyranosyl]-2,7-octadienoyl}acacic acid 28-O-beta-D-glucopyranosyl-(1 --3)-[alpha-L-arabinofuranosyl-(1 --4)]-alpha-L-rhamnopyranosyl-(1 --2)-beta-D-glucopyranosyl ester (2), based on chemical and spectral evidences, named as julibroside J19 and julibroside J18, respectively. Both compounds show significant inhibition action against HeLa, Bel-7402 and MDA-MB-435 cancer cell lines in vitro.