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Organic pigments generally have bright colors but poor ultraviolet (UV) resistance. To improve the UV resistance and extend the applications, a core-shell composite pigment with rutile TiO2 intensification for UV inhibition is proposed by a facile sol-gel method in this work. A core-shell structure, with a homogeneous sol-gel TiO2 shell containing additional nanosized rutile TiO2 particles and with the pigment as the core, was established taking advantage of UV resistance of TiO2 and binding ability of sol-gel. While the sol-gel TiO2 shell alone has already shown obvious ultraviolet shielding effect, as tested over different sol-gel aging times and TiO2 loadings, the UV resistance of the fluorescent pigments was further enhanced by binding the nanosized rutile TiO2 in the sol-gel shell. At a sol-gel TiO2 to rutile TiO2 ratio of 2:1, the UV exposure time is extended about eight times compared with that of the original pigment and twice as that of the modified pigment with pure sol-gel TiO2 for the same color change. Therefore, the novel core-shell composite pigment intensified with nanosized rutile TiO2 particles is proved to be efficient in improving the UV resistance of organic pigments.

Osteosarcoma is known to have a high metastatic potential, which is closely related to angiogenesis. circRNAs are closely associated with osteosarcoma metastasis. This study aims to investigate the role of Circular RNA circFOXP1 in angiogenesis in osteosarcoma. We detected circFOXP1 expression in osteosarcoma, as well as its prognostic value. Tube formation assay and immunohistochemistry staining were conducted to determine the condition of tube formation. RT-qPCR was performed to explore targeted genes. Luciferase reporter assays were carried out to explore the interaction between miR-127-5p, ircFOXP1, and CDKN2AIP, respectively. In vivo studies further confirmed the relationship between circFOXP1 and tumor angiogenesis in osteosarcoma. We found that circFOXP1 expression was increased in osteosarcoma, and could promote angiogenesis in osteosarcoma through upregulating CDKN2AIP expression. Moreover, circFOXP1 could directly bind to miR-127-5p, which further targets CDKN2AIP directly. In conclusion, circFOXP1 promoted angiogenesis by regulating miR-127-5p/CDKN2AIP signaling pathway in osteosarcoma.

Aims. The main treatment for coronary heart disease is percutaneous coronary intervention (PCI), and drug-eluting stents are designed to inhibit vascular smooth muscle cell (VSMCs) proliferation and migration causing restenosis by releasing pharmacological agents into the vessel wall. Once drug-eluting stents are deployed, these pharmacological agents exert many biological effects in the coronary circulation, not only inhibition of VSMCs but also extension to vascular endothelial cells (VECs). The purpose of this study was to explore target molecules that inhibit VSMCs proliferation without affecting VECs. Methods. mRNA and protein expressions of transient receptor potential channels (TRPCs) in cultured VSMCs and VECs were determined by western blotting and RT-qPCR. VSMCs and VECs proliferation was evaluated using CCK-8 assays and western blotting of proliferating cell nuclear antigen (PCNA). Calcium backfilling assays were performed to detect intracellular calcium ion concentration in cultured VSMCs and VECs. Results. The TRPC6 expression was more abundant in VECs than VSMCs, while TRPC4 and TRPC5 expressions were more abundant in VSMCs than VECs. Knockdown of TRPC4 or TRPC5 alone had no remarkable inhibitory effect on VSMC proliferation. Synergistic knockdown of TRPC4 and TRPC5 inhibited the proliferation of VSMCs, declined the expression of the PCNA, and reduced the intracellular calcium ion concentration but not VECs. Conclusion. These data suggest that concurrent inhibition of TRPC4 and TRPC5 inhibits VSMCs proliferation without affecting VECs, thus providing novel targets for developing pharmacological agents for drug-eluting stents.

Purpose: To study the effect of dexmedetomidine on ischemia-reperfusion injury (IRI)–induced inflammatory response, as well as its underlying mechanism of action. Methods: Three groups of healthy adult Sprague Dawley (SD) rats (mean weight, 275 ± 10 g): control, IRI and treatment groups were used. With the exception of control group, ligation was performed on left anterior descending coronary arteries for 30 min and blood perfusion was restored within 100 min to establish IRI. Control group rats were without left ligation. Rats in control and IRI groups received normal saline intraperitoneally 30 min prior to surgery, while the treatment group received 100 μg/kg dexmedetomidine via intraperitoneal injection 30 min before operation. Infarct volume was determined using triphenyl tetrazolium chloride (TTC) staining. IL-6) and TNF-α levels of myocardial tissues and serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine protein expressions of NF-ΚB and TLR-4 in myocardial tissues. Results: Pretreatment with dexmedetomidine markedly decreased infarct volume caused by IRI (p < 0.05). Serum and myocardial TNF-α and IL-6 were significantly upregulated in IRI group, relative to control group, but were downregulated by pretreatment with dexmedetomidine (p < 0.05). There was marked upregulation of NF-ΚB and TLR-4 proteins in IRI rats, relative to untreated rats (p < 0.05). Dexmedetomidine also down-regulated the expressions of these proteins (p < 0.05). Conclusion: Pretreatment with dexmedetomidine alleviates IRI-induced inflammatory reaction via suppression of TLR-4/NF-ΚB signaling pathway. This finding provides a basis for large-scale clinical trials with dexmedetomidine.

Study design Clinical case series. Objective The aim of this study was to propose a novel posterior ligament-bone injury classification and severity (PLICS) score system that can be used to reflect the severity of subaxial cervical fracture dislocations (SCFDs) and predict the failure of anterior-only surgery; and to measure the intraobserver and interobserver reliability of this system. Summary of background data The approach selection for SCFDs is controversial. Although the anterior approach is familiar for most surgeons, postoperative hardware failure and/or delayed cervical deformity is a nonnegligible complication. Methods Ten patients were randomly selected for intraobserver reliability evaluation on two separate occasions, one month apart. Another 30 patients were randomly selected, and the interobserver reliability was measured by comparing results of each case between each reviewer and averaging. To analyze the difference in the PLICS score, 354 patients fulfilled the follow-up were divided into stable and unstable groups according to whether radiologically stable was observed during follow-up. Results For the intraobserver reliability, the mean intraclass correlation coefficient for the 10 reviewers was 0.931. For the interobserver reliability, the mean interobserver correlation coefficient for the three elements was 0.863. Among 16 patients with PLICS score ≥7, two patients in the stable group manifested with severe injury of the posterior ligamentous complex (PLC); extremely unstable lateral mass fractures with or without severe injury of PLC were detected in the 14 patients of the unstable group. Conclusion The proposed PLICS score system showed excellent intraobserver and interobserver reliability. When a PLICS score is >7 or 7 accompanied by extremely unstable lateral mass fractures, the risk of postoperative failure after an anterior-only reconstruction is high and supplemental posterior strengthening can be considered.Level of Evidence: 4.

This study aims to investigate the effect of lymph node examination on overall survival (OS) and lung cancer-specific survival (LCSS) in stage I second primary lung cancer (SPLC) patients who underwent second pulmonary resection. We conducted a retrospective study with the Surveillance, Epidemiology, and End Results (SEER) database to identify stage I SPLC patients who received surgery from 1998 to 2015. The Kaplan–Meier method with landmark analysis and multivariable Cox regression analysis were performed to evaluate the prognostic value of lymph node examination. A total of 842 patients from the SEER database with stage I SPLC who underwent a second surgical treatment were included. The 5-year survival rate was 54.8% for the whole cohort. Multivariable analysis revealed that the number of lymph nodes examined (LNE) was associated with better OS and LCSS in SPLC patients after 12 months postoperatively. Patients with contralateral SPLC had significantly more nodes removed than those with ipsilateral SPLC. For contralateral SPLC, more than 10 LNE was correlated with improved long-term survival outcomes. Ipsilateral SPLC patients benefited from 4 or more LNE. However, the current analysis did not show a significant survival benefit from lymph node examination within 12 months after surgery. For stage I SPLC patients who received surgical treatment after initial resection, an adequate number of LNE would improve both OS and LCSS. We recommend more than 10 LNE for contralateral SPLC and at least 4 LNE for ipsilateral SPLC.

Background The ProCore 25‐gauge needle is a novel specifically designed puncture needle for endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), which may improve the puncture efficiency of the procedure while ensuring the diagnostic rate. The aim of the present study was to evaluate the diagnostic accuracy, mRNA yield, and complication rate of 25‐gauge needles compared to those of 22‐gauge needles in the evaluation of mediastinal and hilar lymphadenopathy. Methods A total of 39 patients undergoing EBUS‐TBNA at our institution were evaluated. All the procedures were performed by an experienced endoscopist formally trained in interventional pulmonology. Both the traditional 22‐gauge and ProCore 25‐gauge needles were used at each lymph node station. For all specimens obtained via EBUS‐TBNA, 50 μL was used to extract mRNA and detect the RNA concentration, whereas the other part was sent to the pathological evaluation. χ2 test and t‐test were performed to determine the differences between the two types of the needles. A P‐value of 0.05). No serious procedure‐related complications were reported. In addition, the mRNA concentration did not differ between the two types of needles (P > 0.05). Conclusion The ProCore 25‐gauge needle gained a similar diagnostic yield with less puncture time and frequency compared with the 22‐gauge needle.

OBJECTIVES The purpose of this study was to evaluate whether quantitative analysis of lower leg muscle enhancement measured from dynamic computed tomographic angiography (dyn-CTA) could be used for diagnosis of peripheral arterial occlusive disease. METHODS Patients (N = 35) with known peripheral arterial occlusive disease underwent the dyn-CTA of calves first. Five minutes later, standard CTA of the peripheral runoff from the diaphragm to the toes was performed. A runoff score was assigned by radiologists as a reference standard for each of 4 lower leg artery segments. The lower leg muscle enhancement measured from the dyn-CTA was analyzed by using quantitative kinetic parameters, including initial enhancement (E1), peak enhancement (Epeak), and enhancement ratio (ER) calculated from average time attenuation curves. In addition, histogram of lower leg muscle enhancement was evaluated by using the first enhanced phase images. RESULTS Lower extremities were diagnosed as a normal group (n = 22) with each vessel segment score equals to 1 or lower and runoff score, 7 or lower, and otherwise as an ischemia group (n = 48). Average ± SD E1 is 91.4% ± 8.5% and 82.3% ± 10.7%, Epeak is 122.7% ± 10.4% and 115.6% ± 11.1%, and ER is 0.75 ± 0.05 and 0.72 ± 0.09 for normal and ischemia group, respectively. Statistical analysis showed that average E1 and Epeak for the ischemia group were significantly lower (P < 0.05) than the normal group. The histogram analysis demonstrated that mean and median of muscle enhancement in the ischemia group were significantly smaller (P < 0.05), and coefficient of variation (CV) was significantly larger (P < 0.05) than the normal group. There were weak negative correlations (r = -0.42, P < 0.05) between runoff scores and E1 and Epeak, and weak positive correlation (r = 0.40, P < 0.05) between runoff scores and CV. The receiver operating characteristics analysis between the 2 groups had area under the curve of 0.77 and 0.76 for E1 and CV, respectively. CONCLUSIONS Lower leg muscle enhancement measured from the dyn-CTA could be assessed quantitatively to assist diagnosis of ischemia in clinical practice.

Phenolic acid glycerols (PAGs) are a group of rare phytochemicals found from potato periderm, which show great potential in the food, cosmetic and pharmaceutical industries. In this study, seven PAGs were enzymatically synthesized via transesterification of ethyl phenates (EPs) with glycerol by ultrasonic promotion. The conversions of 88.1–98.5% could be obtained in 1–9 h. Compared with the conventional stirring methods, the catalytic efficiency was significantly increased 11.0–44.0 folds by ultrasound assistance. The lipid peroxidation inhibition activity increased 8.1-fold and 14.4-fold compared to the parent phenolic acids (PAs). Furthermore, caffeoyl glycerol and feruloyl glycerol exhibited excellent antimicrobial activity against Escherichia coli compared to the corresponding PAs with minimum inhibitory concentration (MIC) decreasing 4–16-fold. The PAGs can also absorb a much wider and higher amount of the harmful UV-B rays than the corresponding PAs. The present strategy for facile synthesis of multifunctional PAGs paves the way for the development and application of natural phytochemicals and novel ingredients.

Background To evaluate the association of physical activity (PA) intensity with cognitive performance at baseline and during follow-up. Methods A total of 4039 participants aged 45 years or above from the China Health and Retirement Longitudinal Study were enrolled in visit 1 (2011–2012) and followed for cognitive function in visit 2 (2013–2014), visit 3 (2015–2016), and visit 4 (2017–2018). We analyzed the association of PA intensity with global cognition, episodic memory, and mental intactness at baseline using adjusted regression methods and evaluated the long-term effect of PA intensity using multiple measures of cognition scores by mixed effect model. Results In cross-sectional analysis, mild and moderate PA, rather than vigorous PA, was associated with better cognitive performance. The results remained consistent in multiple sensitivity analyses. During the follow-up, participant with mild PA had a 0.56 (95% CI 0.12–0.99) higher global cognition, 0.23 (95% CI 0.01–0.46) higher episodic memory, and 0.33 (95% CI 0.01–0.64) higher mental intactness, while those with moderate PA had a 0.74 (95% CI 0.32–1.17) higher global score, 0.32 (95% CI 0.09–0.54) higher episodic memory, and 0.43 (95% CI 0.12–0.74) higher mental intactness, compared with individuals without PA. Vigorous PA was not beneficial to the long-term cognitive performance. Conclusions Our study indicates that mild and moderate PA could improve cognitive performance, rather than the vigorous activity. The targeted intensity of PA might be more effective to achieve the greatest cognition improvement considering age and depressive status.

Background: Vogt-Koyanagi-Harada (VKH) disease is a multisystem autoimmune disorder which could induce bilateral panuveitis involving the posterior pole and peripheral fundus. Optical coherence tomography angiography (OCTA) provides several advantages over traditional fluorescence angiography for revealing pathological abnormalities of the retinal vasculature. Until recently, however, the OCTA field of view (FOV) was limited to 6 × 6 mm2 scans.Purpose: This study examined retinal vasculature and choriocapillaris abnormalities across multiple regions of the retina (15 × 9 mm2 wide field, macular, peripapillary regions) among acute and convalescent VKH patients using a novel widefield swept-source OCTA (WSS-OCTA) device and assessed correlations between imaging features and best-corrected visual acuity (BCVA).Methods: Twenty eyes of 13 VHK disease patients in the acute phase, 30 eyes of 17 patients in the convalescent phase, and 30 eyes of 15 healthy controls (HCs) were included in this study. Vascular length density (VLD) in superficial and deep vascular plexuses (SVP, DVP), vascular perfusion density (VPD) in SVP, DVP, and choriocapillaris (CC), and flow voids (FV) in CC were measured across multiple retinal regions via WSS-OCTA (PLEX Elite 9000, Carl Zeiss Meditec Inc., USA) using the 15 × 9 mm2 scan pattern centered on the fovea and quantified by ImageJ.Results: Compared to HCs, acute phase VKH patients exhibited significantly reduced SVP-VLD, SVP-VPD, and CC-VPD across multiple retinal regions (all p < 0.01). Notably, the FV area was more extensive in VKH patients, especially those in the acute phase (p < 0.01). These changes were reversed in the convalescent phase. Stepwise multiple linear regression analysis demonstrated that macular DVP-VLD and macular CC-VPD were the best predictive factors for BCVA in the acute and convalescent VKH groups.Conclusion: The wider field of SS-OCAT provides more comprehensive and detailed images of the microvasculature abnormalities characterizing VKH disease. The quantifiable and layer-specific information from OCTA allows for the identification of sensitive and specific imaging markers for prognosis and treatment guidance, highlighting WSS-OCTA as a promising modality for the clinical management of VKH disease.

Background Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. Methods We performed an endoscopic examination of 44,857 individuals aged 40–69 years from five high incidence regions of China in 2017–2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. Results We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52–3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03–3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05–1.37) was essential risk factor of LGIN. Conclusions Among individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Objective This study investigated the relationship between pain location and fracture type in patients with acute osteoporotic vertebral fracture (OVF). Design A prospective observational study. Subject A total of 306 patients with acute OVF were included. Methods The site of pain of each patient was recorded, and the patients were divided into a group with pain at the fracture site (group 1) and a group with pain at a non-fracture site (group 2). Fractures were classified into four types: type I, upper endplate type; type II, central type; type III, lower endplate type; and type IV, burst type. Results There were 146 patients in group 1, of whom 20.55% (30/146) had type I fractures, 33.56% (49/146) had type II fractures, 15.75% (23/146) had type III fractures, and 30.14% (44/146) had type IV fractures. There were 227 patients in group 2, of whom 57.27% (130/227) had type I fractures, 5.29% (12/227) had type II fractures, 35.24% (80/227) had type III fractures, and 2.20% (5/227) had type IV fractures. There was a statistical difference in the fracture type distribution between the two groups (P Conclusions For patients with acute OVF, the site of pain is related to the type of fracture. The pain at the fracture site is more often observed in the central type and burst type of fractures, whereas pain at a non-fracture site is more often observed in the upper and lower endplate types of fractures. Additionally, when OVF is suspected, radiological assessment of the thoracic and lumbar spine is recommended to better detect fractures that could cause pain distal to the site of the fracture.

Background: Fusion with a titanium mesh cage (TMC) has become popular as a conventional method after cervical anterior corpectomy, but postoperative TMC subsidence has often been reported in the literature. We designed a novel anatomic cervical TMC to reduce the postoperative subsidence rate. This finite element study aims to investigate the anti-subsidence performance of a novel anatomic TMC and provide a theoretical basis for clinical application. Methods: According to the test process specified in the ASTM F2267 standard, three-dimensional finite element analysis was used to compare the anti-subsidence characteristics of a traditional TMC (TTMC) and novel TMC (NTMC). Abaqus software was used for the mesh, and the modulus of elasticity, Poisson's ratio and other material coefficients of each part were input into the model. Solidworks software was used to establish the TTMC and NTMC models and construct the two three-dimensional finite element models of TMC subsidence testing mentioned above. Through analysis, the relationships between the stiffness of the intervertebral body fusion device (Kd) and the stiffness of the polyurethane foam blocks (Ks) of the TTMC and NTMC were derived, respectively. Results: After fitting the linear segment, the Kd values of the TTMC and NTMC were 37314 N/mm and 89124 N/mm, respectively. After calculation, the Ks values of the TTMC and NTMC were 653.83 N/mm and 995.95 N/mm, respectively. The Kp values of the TTMC and NTMC were calculated to be 665.5 N/mm and 1007.2 N/mm according to the formula. Conclusion: The reported novel anatomic titanium mesh cage (NTMC) significantly improved the anti-subsidence performance after ACCF, which was approximately 51.3% higher than that of the traditional titanium mesh cage.

BACKGROUND Preoperative estimation of hepatocellular carcinoma (HCC) recurrence after conventional transcatheter arterial chemoembolization (c-TACE) is crucial for subsequent follow-up and therapy decisions. PURPOSE To evaluate the associations of radiomics models based on pretreatment contrast-enhanced MRI, a clinical-radiological model and a combined model with the recurrence-free survival (RFS) of patients with HCC after c-TACE, and to develop a radiomics nomogram for individual RFS estimations and risk stratification. STUDY TYPE Retrospective. POPULATION In all, 184 consecutive HCC patients. FIELD STRENGTH/SEQUENCE 1.5T or 3.0T, including T2 WI, T1 WI, and contrast-enhanced T1 WI. ASSESSMENT All HCC patients were randomly divided into the training (n = 110) and validation datasets (n = 74). Radiomics signatures capturing intratumoral and peritumoral expansion (1, 3, and 5 mm) were constructed, and the radiomics models were set up using least absolute shrinkage and selection operator (LASSO) Cox regression. Clinical-radiological features were identified by univariate and multivariate Cox regression. The clinical-radiological model and the combined model fusing the radiomics signature with the clinical-radiological risk factors were developed by a multivariate Cox proportional hazard model. A radiomics nomogram derived from the combined model was established. STATISTICAL TESTS LASSO Cox regression, univariate and multivariate Cox regression, Kaplan-Meier analysis were performed. The discrimination performance of each model was quantified by the C-index. RESULTS Among the different peritumoral expansion models, only the 3-mm peritumoral expansion model (C-index, 0.714) showed a comparable performance (P = 0.4087) to that of the portal venous phase intratumoral model (C-index, 0.727). The combined model showed the best performance and the C-index was 0.802. Kaplan-Meier analysis showed that the cutoff values of the combined model relative to a median value (1.7426) perfectly stratified these patients into high-risk and low-risk subgroups. DATA CONCLUSION The combined model is more valuable than the clinical-radiological model or radiomics model alone for evaluating the RFS of HCC patients after c-TACE, and the radiomics nomogram can be used to preoperatively and individually estimate RFS. LEVEL OF EVIDENCE 3 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;52:461-473.

Purpose This study aimed to evaluate Atorvastatin (ATO)-associated hepatotoxicity using prescription sequence symmetry analysis (PSSA), based on a health insurance database of a Chinese population living in Jiangsu Province, China. Methods Patients prescribed ATO and hepatoprotective drugs in 2017 were identified, and the run-in period was determined based on the "waiting-time" distribution. Adjusted sequence ratio (ASR) and 95% confidence interval (95% CI) were calculated to estimate the risk of ATO-associated hepatotoxicity under different time intervals or based on gender and age stratification. Results A total of 2,549 patients, with 1,518 filling the ATO prescription first and 1,031 filling the ATO prescription second, were analyzed. After setting the run-in period as 30 days and the time interval as 15, 30, 60, 90, 120, and 180 days, the ASRs were 1.492 (95% CI: 1.367-1.652), 1.399 (95% CI: 1.308-1.508), 1.280 (95% CI: 1.213-1.357), 1.292 (95% CI: 1.234-1.356), 1.278 (95% CI: 1.226-1.336), and 1.274 (95% CI: 1.229-1.323), respectively. No significant difference was observed between different genders and ages (χ2=0.161, P=0.688; χ2=1.565, P=0.211, respectively). Conclusion This is the first study conducted in a real-world setting to evaluate the relationship between ATO and hepatotoxicity using the PSSA in a Chinese population. We found a 1.3- to 1.5-fold increase in risk of hepatotoxicity following ATO, with the greater risk occurring within the first 30 days of treatment.

WHAT IS KNOWN AND OBJECTIVE Reactive metabolites from anti-tuberculosis (anti-TB) drugs can result in abnormal accumulation of reactive oxygen species (ROS), which plays an important role in anti-TB drug-induced liver injury (ATLI). Liver cells could keep the production of ROS in balance by antioxidant activities. The heme oxygenase 1, encoded by the HMOX1 gene and NADH:quinone oxidoreductase 1, encoded by the NQO1 gene are crucial mediators of cellular defense against ROS. The present study aimed to investigate the associations between HMOX1 and NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. METHODS A matched case-control study was conducted using 314 ATLI cases and 628 controls. Multivariate conditional logistic regression analysis was used to estimate the association between genotypes and risk of ATLI by the odds ratios (ORs) with 95% confidence intervals (CIs), with weight and use of hepatoprotectant as covariates. RESULTS AND DISCUSSION Patients carrying the GG genotype at rs2071748 in HMOX1 were at a higher risk of ATLI than those with the AA genotype (adjusted OR = 1.503, 95% CI: 1.005-2.249, P = 0.047), and significant differences were also found under the recessive (P = 0.015) and additive (P = 0.045) models. Subgroup analysis confirmed the relationship in mild hepatotoxicity cases under the recessive and additive models (adjusted OR = 1.714, 95% CI: 1.169-2.513, P = 0.006; adjusted OR = 1.287, 95% CI: 1.015-1.631, P = 0.037, respectively). WHAT IS NEW AND CONCLUSION This is the first study to explore the relationship between HMOX1, NQO1 polymorphisms and ATLI in Chinese anti-TB treatment population. Based on a matched case-control study, genetic polymorphisms of HMOX1 may be associated with susceptibility to ATLI in the Chinese population.

Background The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. Methods GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. Results We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. Conclusion In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

In this study, the degradation of sulfonamide antibiotics was investigated through persulfate-enhanced UV advanced oxidation process. Factors that may affect the degradation efficiency were analyzed. Results showed that the persulfate imposed a significant enhancement on the UV oxidation process during the sulfathiazole degradation. The combined process of UV/persulfate can effectively remove about 96% of sulfathiazole within 60 min. With the increase in the dosage of persulfate, the removal efficiency increased as well. Different water matrix almost had no effect on the removal efficiency. Two intermediates were found during the sulfathiazole degradation. It can be predicted that the combined process of UV/persulfate has a broad application prospect for removing sulfonamide antibiotics in water treatment.

Far less has been unveiled about the functions of lncRNAs on cancers yet. Here, we reported that lncRNA FAM87A, as a ceRNA of miR-424-5p, played a vital role in glioma development. qRT-PCR result indicated that FAM87A was abnormally downregulated in glioma tissue and cells. Survival analysis suggested that the FAM87A expression was negatively correlated with the survival rate. Effects of FAM87A on human glioma cell lines were also analyzed by MTT, Edu, and transwell assays. FAM87A hastened proliferation and migration of glioma cells. MiR-424-5p, predicted target of FAM87A, was fostered in glioma, which was examined by qRT-PCR. A negative correlation was indicated between FAM87A and miR-424-5p. Results of bioinformatics, dual luciferase, and RIP assays unveiled that FAM87A and miR-424-5p act upon each other. In addition, miR-424-5p targeted 3 ′ -UTR of PPM1H. Also, effects of miR-424-5p/FAM87A on glioma cells were identified via the cell function experiments. FAM87A suppressed PPM1H by binding to miR-424-5p competitively, thereby restraining cell proliferation, migration, and invasion. Collectively, these findings illuminated a new mechanism for glioma progression. Therefore, FAM87A may act as a feasible target for glioma treatment.

Coronavirus infectious disease (COVID-19), caused by deadly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared as a pandemic by the World Health Organization. This disease has become the world’s worst infectious disease, killing about 1.05 million lives as of September 2020. The absence of vaccines and effective drugs is a key trouble responsible for the ineffective management of this pandemic. Considering this emergency situation, several trials have been made to identify repurposing on-market drugs known for their antiviral behavior. Several modern technologies such as deep machine learning are used to combat this deadly disease with faster prediction and greater accuracy. More interestingly, these studies have provided clues for the antiviral properties and are believed to help in effective control of this pandemic. The drugs identified by deep learning-based virtual screening will help in unraveling molecular mechanisms of therapeutic and antiviral properties and will pave the way for designing artificial drugs. Hence we focus in this chapter on the integrated applications of deep learning models as a pipeline for drug and vaccine discovery which has implications in therapeutic drug targeting for COVID-19.

Identification of molecules specific to the retinal neovasculature will promote antiangiogenic therapy with enhanced targeting ability. The specificity of phage-displayed peptide GX1 (a cyclic 7-mer peptide motif CGNSNPKSC) to gastric cancer neovasculature has been extensively confirmed both in vitro and in vivo. To investigate the potential application of GX1 in antiangiogenic therapy targeting retinal angiogenesis-related diseases, we performed immunohistochemistry and immunofluorescence analyses. GX1 demonstrated positive staining in the retinal neovasculature in an oxygen-induced mouse model of retinopathy (OIR) as well as in rat retinal microvasculature endothelial cells (RMECs), confirming the major role of the GX1 receptor during retinal angiogenesis. Dimeric GX1 was synthesized to increase the binding affinity to the GX1 receptor, and the antiangiogenic effects were examined in RMECs in vitro and the retinal neovasculature in the OIR in vivo. Cell proliferation was evaluated using a Cell Counting Kit-8 (CCK-8) assay, revealing that compared with the GX1 monomer, dimeric GX1 significantly inhibited RMEC proliferation (P 0.05). This finding may be attributed to the enhanced (P 0.05) apoptosis induced by dimeric GX1 in RMECs based on results obtained from TUNEL, flow cytometric and cell cycle analyses. In RMECs, in vitro cell migration and tube formation were significantly inhibited following exposure to dimeric GX1. Intravitreal administration of dimeric GX1 resulted in a greater reduction in the retinal neovascularization in vivo than administration of the GX1 monomer (P 0.05). In conclusion, dimeric GX1 showed greater inhibition of angiogenesis than monomeric GX1 and could be a promising agent for antiangiogenic therapy in retinal angiogenesis-related diseases.

Background Orthodontic treatment is widely used to treat malocclusion. However, the influence of treatment on the oral microbiome remains unclear. In this study, we investigated salivary microbial changes in patients undergoing orthodontic treatment. Methods In total, 19 orthodontic patients participated in this study. Saliva samples were collected at the following three timepoints: before (T0) and 3 months (T1) and 6 months (T2) after the placement of orthodontic appliances. High-throughput sequencing was performed based on the 16S rRNA gene V4 region. Results The phyla of Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria and Fusobacteria were predominant. Observed Species, Chao1 and ACE, which represent α diversity, were significantly decreased at T1 and subsequently increased at T2. In addition, the β diversity at T1 based on the Bray-Curtis distances differed from T0 and T2. The relative abundances of Prevotella, Porphyromonas and Peptostreptococcus were decreased with treatment, whereas those of Capnocytophaga and Neisseria exhibited the opposite results. In total, 385 of 410 operational taxonomic units were shared at T0, T1 and T2. The co-occurrence networks with hub nodes at T1 were the most complex. Conclusion Orthodontic treatment temporarily affected the saliva microbial community. This dynamic alteration in species did not induce deterioration in oral health. Oral hygiene instructions were necessary and should be emphasized during each visit. Further studies with longer observation periods and more participants are required.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus poses serious threats to the global public health and leads to worldwide crisis. No effective drug or vaccine is readily available. The viral RNA-dependent RNA polymerase (RdRp) is a promising therapeutic target. A hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected market available drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008μM and 9.453 μM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of fast and accurate anti-viral drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19., Author summary Currently, a novel coronavirus called SARS-COV-2 is spreading across many parts of the world. Unfortunately, there is still a lack of effective drugs against the virus. Additionally, it usually takes much longer time to develop a new drug using traditional methods. Thus, it is now better to rely on some alternative methods to develop drugs that can treat such a disease effectively. In this paper, we have proposed a deep learning and molecular dynamics simulation based hybrid drug screening procedure for identifying potential drug candidates targeting RdRp from 1906 market available drugs. Our screening have successfully identified a FDA-approved drug called Pralatrexate that strongly inhibits the replication of 2019-nCoV in vitro with EC50 values of 0.008μM. This work demonstrated the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

To assess the knowledge, awareness, practice patterns, and attitudes of Chinese dermatologists toward psychocutaneous disorders and explore their interest in continuing medical education (CME) of psychodermatology. An online survey study was conducted from October to November 2019. The survey questionnaire link was sent to the members of the national and local association of dermatology through a social media App. After confirming the informed consent to enrol in the study, the participants filled out the online questionnaire anonymously. About 1047 dermatologists completed the survey. The most common diagnoses referred to the psychiatrist from Chinese dermatologists were venereal phobia (51.77%), delusion of parasitosis (44.03%), and trichotillomania (32.28%). Compared with dermatologists, Traditional Chinese Medicine (TCM) dermatologists had less training experience on psychodermatologic CME (4.21% vs 8.34% who had attending more than twice CME, P .05). Although TCM dermatologist experience more frequency with psychodermatology (24.21% TCM vs 15.71% dermatologists), they had lower comfort level in treating psychodermatologic patients (51.58% TCM vs 58.89% dermatologist) (P .05). While 818 (78.13%) dermatologists never received any training course, 84.53% of the dermatologists expressed interest in attending CME events on psychodermatology. The most popular CME themes of psychodermatology were emotional disorders related to skin diseases, delusion of parasitosis, and trichotillomania. Chinese dermatologists have insufficient knowledge and awareness toward psychodermatology. TCM dermatologists have higher awareness on psychocutaneous diseases compared with dermatologists. Psychodermatology continuing medical education programs should be carried out as soon as possible.

When vertebroplasty is used to treat Kummell disease with bone deficiency at the vertebral anterior border, bone cement displacement often occurs intraoperatively or postoperatively. We designed and used a new bone cement screw system to avoid this serious complication. The purpose of this study was to evaluate the safety and effectiveness of this novel operation method through more than 3 years of follow-up.From January 2014 to August 2016, 27 patients suffering from single-segment Kummell disease with bone deficiency at the vertebral anterior border were treated by vertebroplasty combined with a novel bone cement screw. Bone cement was released into the diseased vertebrae through the screw to fully fill the intravertebral vacuum cleft. Screw fixation of bone cement can avoid intraoperatively or postoperatively displacement. All patients received surgery involving a unilateral technique, and only one screw was implanted in each patient. The clinical efficacy was evaluated using Odom's criteria and statistical analysis of the vertebral body index (VBI), vertebral body angle (VBA), bisegmental Cobb angle (BCA), visual analogue scale (VAS), Oswestry disability index (ODI), and the results of the MOS 36-item short form health survey (SF-36).The operation was completed successfully in 27 cases. The average operation time was 49.63 ± 10.82 min, and the average volume of cement injected was 4.70 ± 0.87 mL. The patients' preoperative VBI, VBA, BCA, VAS and ODI scores were 43.11 ± 5.94, 21.04 ± 2.55, 45.00 ± 6.26, 7.59 ± 0.84, and 79.85 ± 7.58, respectively. The postoperative measurements were 78.70 ± 2.55, 12.70 ± 2.11, 26.11 ± 4.73, 3.22 ± 0.93 and 50.04 ± 9.28, respectively. At the last follow-up, the measurements were 78.04 ± 2.30, 13.15 ± 2.38, 27.07 ± 4.87, 2.04 ± 0.65, and 22.85 ± 5.06, respectively. There was a significant difference between the preoperative and postoperative data, as well as the preoperative and the last follow-up data (P 0.05). Comparing the results of SF-36 before operation and at the last follow-up revealed significant differences in physical function, role-physical, body pain, vitality, and social function (P 0.05). However, there were no significant differences in general health, emotional function and mental health. Finally, 26 patients (96.3 %) had good to excellent clinical outcomes according to Odom's criteria.This 3-year follow-up study shows that the novel bone cement screw system combined with vertebroplasty has a good short and medium-term therapeutic effect in patients with Kummell disease and bone deficiency at the vertebral anterior border, while its long-term efficacy is subject to further studies.

Background The purpose of this study is to evaluate a new method involving time maximum intensity projection (t-MIP) postprocessed from dynamic computed tomographic angiography (dyn-CTA) in diagnosing peripheral arterial disease (PAD). Methods A population of 34 patients with known PAD was examined with a combined CTA protocol consisting of a standard CTA (s-CTA) scan of the lower extremities and a dyn-CTA scan of the calves. For each lower leg, t-MIP images consisting of the MIP0 (sagittal MIP), MIP+θ (45° lateral MIP), and MIP−θ (− 45° lateral MIP) were automatically generated from dyn-CTA. An objective evaluation of the vascular CT attenuation of the best enhancement phase of dyn-CTA and t-MIP was measured; a subjective evaluation of vessel stenosis and occlusion was performed, assigning a score for t-MIP and s-CTA. The CT attenuation of t-MIP and dyn-CTA was compared, as were the runoff scores of t-MIP and s-CTA. Results The CT attenuation of t-MIP CTA of three vascular segments from 68 lower extremities was higher than that of the best enhancement phase of dyn-CTA and s-CTA, with statistically significant differences at the posterior tibial artery and fibular artery (all p Conclusions There is potential clinical applicability of t-MIP in assisting with the diagnosis of lower leg vascular stenosis in dyn-CTA with reliable diagnostic accuracy and convenient immediacy.

Purpose To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with different areas of right retroperitoneal space (rRPS) invasion and analyze the blood supply. Methods This retrospective study enrolled 41 patients with HCC with different areas of rRPS invasion treated with TACE, including 22 HCCs with superior aspect of the right perirenal space (SARPS) invasion and 19 HCCs with right anterior pararenal space (RAPS) invasion. The overall response rate (ORR) and disease control rate (DCR) were analyzed. The prognostic factors for overall survival (OS) after TACE were determined. The blood supply characteristics of HCC with different areas of rRPS invasion were analyzed with arteriograms. Results All patients underwent 2.8 ± 1.8 TACE sessions over 25.0 ± 21.9 months. The median OS was 29.0 months for patients with SARPS invasion and 12.0 months for patients with RAPS invasion (P = 0.004). Only the invaded area of the rRPS was an independent prognostic factor for OS [hazard ratio (HR), 2.833; 95% CI, 1.297-6.188; and P = 0.009). The ORR and DCR were significantly higher in the group with SARPS invasion than in the group with RAPS invasion (ORR: 63.6% vs 31.6%, P = 0.041; DCR: 77.3% vs 47.4%, P = 0.047). Initially, HCC with SARPS invasion were supplied by the hepatic artery (HA; n = 8) and both the HA and extrahepatic collateral vessels (EHCs; n = 14); HCC with RAPS invasion were supplied by the HA (n = 10) and both the HA and EHCs (n = 9); as the TACE sessions increased, the tumor-feeding vessels shifted from the HA to both the HA and EHCs, and even EHCs could be the only blood supply. Rare EHCs appeared earlier and more frequently in the RAPS group than in the SARPS group. Conclusion The efficacy of TACE differed for HCC with different areas of rRPS invasion, and the median OS, ORR and DCR were significantly better in the SARPS group than in the RAPS group. Different common EHCs supplied HCCs with different areas of rRPS invasion, while other rare EHCs appeared more frequently in the RAPS group.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses serious threats to the global public health and leads to an unprecedented worldwide crisis. Unfortunately, no effective drugs or vaccines are available till now. Since the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a promising therapeutic target, a deep learning and molecular simulation based hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected FDA-approved drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008µM and 9.453 µM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

Background A number of studies have reported hyperprogressive disease (HPD) in non-small cell lung cancer (NSCLC) after treatment with immune checkpoint inhibitor (ICI). This study aimed to summarize the incidence and survival outcome of HPD in NSCLC and identify the clinicopathological features associated with HPD based on available eligible studies. Methods Four databases (Medline/PubMed, Embase, Web of Science, and Cochrane Library) were searched for eligible studies on HPD published before January 23, 2020, to evaluate the incidence, outcome, and clinical features of HPD. Statistical analyses were performed using STATA 15.0. All meta-analyses were performed based on the random-effects model. Results This study included 6 studies involving 1389 patients. The incidence of HPD ranged from 8.02 to 30.43%. Compared with patients with non-HPD, those with HPD were associated with worse overall survival. We identified that Eastern Cooperative Oncology Group > 1, Royal Marsden Hospital score ≥ 2, serum lactate dehydrogenase > upper limit of normal, the number of metastasis sites > 2, and liver metastasis were associated with the risk of HPD. Conclusions This study summarized the clinical features of HPD in NSCLC patients. The meta-analysis showed that five pre-treatment clinicopathological features might be associated with HPD, which may help in selecting patients for ICIs.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses serious threats to the global public health and leads to an unprecedented worldwide crisis. Unfortunately, no effective drugs or vaccines are available till now. Since the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a promising therapeutic target, a deep learning and molecular simulation based hybrid drug screening procedure was proposed and applied to identify potential drug candidates targeting RdRp from 1906 approved drugs. Among the four selected FDA-approved drug candidates, Pralatrexate and Azithromycin were confirmed to effectively inhibit SARS-CoV-2 replication in vitro with EC50 values of 0.008µM and 9.453 µM, respectively. For the first time, our study discovered that Pralatrexate is able to potently inhibit SARS-CoV-2 replication with a stronger inhibitory activity than Remdesivir within the same experimental conditions. The paper demonstrates the feasibility of accurate virtual drug screening for inhibitors of SARS-CoV-2 and provides potential therapeutic agents against COVID-19.

A novel coronavirus, called 2019-nCoV, was recently found in Wuhan, Hubei Province of China, and now is spreading across China and other parts of the world. Although there are some drugs to treat 2019-nCoV, there is no proper scientific evidence about its activity on the virus. It is of high significance to develop a drug that can combat the virus effectively to save valuable human lives. It usually takes a much longer time to develop a drug using traditional methods. For 2019-nCoV, it is now better to rely on some alternative methods such as deep learning to develop drugs that can combat such a disease effectively since 2019-nCoV is highly homologous to SARS-CoV. In the present work, we first collected virus RNA sequences of 18 patients reported to have 2019-nCoV from the public domain database, translated the RNA into protein sequences, and performed multiple sequence alignment. After a careful literature survey and sequence analysis, 3C-like protease is considered to be a major therapeutic target and we built a protein 3D model of 3C-like protease using homology modeling. Relying on the structural model, we used a pipeline to perform large scale virtual screening by using a deep learning based method to accurately rank/identify protein–ligand interacting pairs developed recently in our group. Our model identified potential drugs for 2019-nCoV 3C-like protease by performing drug screening against four chemical compound databases (Chimdiv, Targetmol-Approved_Drug_Library, Targetmol-Natural_Compound_Library, and Targetmol-Bioactive_Compound_Library) and a database of tripeptides. Through this paper, we provided the list of possible chemical ligands (Meglumine, Vidarabine, Adenosine, d-Sorbitol, d-Mannitol, Sodium_gluconate, Ganciclovir and Chlorobutanol) and peptide drugs (combination of isoleucine, lysine and proline) from the databases to guide the experimental scientists and validate the molecules which can combat the virus in a shorter time. Electronic supplementary material The online version of this article (10.1007/s12539-020-00376-6) contains supplementary material, which is available to authorized users.

Background This article reports the effects of proenkephalin (PENK) on osteosarcoma (OS) cell migration. Methods A Gene Expression Omnibus (GEO) dataset was used to identify differentially expressed genes (DEGs) in OS tumor samples and normal human osteoblasts. Tumor tissue and adjacent normal tissue were collected from 40 OS patients. MG63 cells were transfected with si-PENK. Transwell migration assays and wound healing assays were performed to compare the effect of PENK on migration. Moreover, LY294002 was used to identify the potential mechanism. Gene expression was examined via qRT-PCR and Western blotting. Results Bioinformatic analysis revealed that PENK was downregulated in OS tumor samples compared with normal human osteoblasts. Moreover, PENK was identified as the hub gene of the DEGs. The PI3K/Akt signaling pathway was significantly enriched in the DEGs. Moreover, PENK was downregulated in OS and MG63 cells compared with the corresponding control cells. Silencing PENK promoted MG63 cell migration; however, treatment with LY294002 partially attenuated PENK silencing-induced OS cell migration. Conclusion PENK inhibits OS cell migration by activating the PI3K/Akt signaling pathway.