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Fluorescence imaging is a noninvasive and dynamic real-time imaging technique; however, it exhibits poor spatial resolution in centimeter-deep tissues because biological tissues are highly scattering media for optical radiation. The recently developed ultrasound-controlled fluorescence (UCF) imaging is a novel imaging technique that can overcome this bottleneck. Previous studies suggested that the effective contrast agent and sensitive imaging system are the two pivotal factors for generating high-resolution UCF images ex vivo and/or in vivo. Here, this review highlights the recent advances (2015–2020) in the design and synthesis of contrast agents and the improvement of imaging systems to realize high-resolution UCF imaging of deep tissues. The imaging performances of various UCF systems, including the signal-to-noise ratio, imaging resolution, and imaging depth, are specifically discussed. In addition, the challenges and prospects are highlighted. With continuously increasing research interest in this field and emerging multidisciplinary applications, UCF imaging with higher spatial resolution and larger imaging depth may be developed shortly, which is expected to have a far-reaching impact on disease surveillance and/or therapy.

Silicosis is an occupational disease caused by inhalation of silica dust, which is hallmarked by progressive pulmonary fibrosis associated with poor prognosis. Wnt/β-catenin signaling is implicated in the development of fibrosis and is a therapeutic target for fibrotic diseases. Previous clinical studies of patients with pneumoconiosis, including silicosis, revealed an increased concentration of circulating WNT3A and DKK1 proteins and inflammatory cells in bronchoalveolar lavage compared with healthy subjects. The present study evaluated the effects of adenovirus-mediated transduction of Dickkopf-1 (Dkk1), a Wnt/β-catenin signaling inhibitor, on the development of pulmonary silicosis in mice. Consistent with previous human clinical studies, our experimental studies in mice demonstrated an aberrant Wnt/β-catenin signaling activity coinciding with increased Wnt3a and Dkk1 proteins and inflammation in lungs of silica-induced silicosis mice compared with controls. Intratracheal delivery of adenovirus expressing murine Dkk1 (AdDkk1) inhibited Wnt/β-catenin activity in mouse lungs. The adenovirus-mediated Dkk1 gene transduction demonstrated the potential to prevent silicosis development and ameliorate silica-induced lung fibrogenesis in mice, accompanied by the reduced expression of epithelia--mesenchymal transition markers and deposition of extracellular matrix proteins compared with mice treated with "null" adenoviral vector. Mechanistically, AdDkk1 is able to attenuate the lung silicosis by inhibiting a silica-induced spike in TGF-β/Smad signaling. In addition, the forced expression of Dkk1 suppressed silica-induced epithelial cell proliferation in polarized human bronchial epithelial cells. This study provides insight into the underlying role of Wnt/β-catenin signaling in promoting the pathogenesis of silicosis and is proof-of-concept that targeting Wnt/β-catenin signaling by Dkk1 gene transduction may be an alternative approach in the prevention and treatment of silicosis lung disease.

Background Posterior hypopharyngeal carcinoma indicates a poor prognosis. Previous treatments predicted negative influence to the pronunciation and swallowing function. The present study focuses on improving survival rate while improving quality of life. Aim To investigate on the surgical techniques of the preservation of laryngeal function of posterior hypopharyngeal carcinoma. Methods Eighteen patients with posterior hypopharyngeal carcinoma of T2-T3 were studied. All primary lesions were removed and the defects were repaired with the radial forearm free flap (RFFF). Results The 3-year overall survival rate was 51.9%. All patients could maintain daily caloric intake by feeding orally, and remove the gastric tube 28-61 days after operation. Assessed swallowing function by Fiberoptic endoscopic evaluations of swallowing. When eating solid food, 66.67% patients had food residue; no food entered airway, and all patients had Penetration-Aspiration Scale of level 1. As for liquid, 11.11% patients had level 5, 16.67% level 4, 27.78% level 2 and 44.44% level 1. Conclusions By preserving the integrity of larynx and superior laryngeal nerve with repairing the defects of posterior wall of hypopharynx with RFFF, patients with T2 and T3 stage posterior hypopharyngeal carcinoma could live a better quality of life.

The advantages of urgent-start peritoneal dialysis (PD) vis-a-vis urgent-start hemodialysis (HD) are not clear. We performed a systematic review and meta-analysis of studies comparing the two modalities. Databases of PubMed, Embase, Ovoid, and Google Scholar were searched up to November 1, 2020. The primary outcome was mortality, and secondary outcomes were dialysis-related infectious complications and mechanical complications. Risk ratios (RRs) were calculated for all outcomes. Seven studies were included. The pooled analysis revealed a statistically significant reduced risk of all-cause mortality in patients undergoing urgent-start PD as compared to urgent-start HD (RR: 0.61, 95% confidence interval [CI] [0.40, 0.94], I2 = 56.34%). A meta-analysis of dialysis-related infectious complications indicated no statistically significant difference between the two modalities (RR: 0.66, 95% CI [0.29, 1.50], I2 = 69.62%). Our analysis revealed a statistically significant reduced risk of mechanical complications in patients undergoing urgent-start PD (RR: 0.54, 95% CI [0.40, 0.73], I2 = 0%). To conclude, unadjusted data from observational studies are indicative of lower mortality and lower risk of mechanical complications with urgent-start PD versus urgent-start HD. The risk of infectious complications was not different between the two groups. Further studies with a larger sample size using propensity-matched cohorts are needed to strengthen current evidence.

Background The histological grade of bladder cancer (BCa) is an important factor associated with the treatment and prognosis. However, accurate determination of the preoperative histological grade of BCa remains a challenge. Purpose To investigate the diagnostic potential of synthetic MRI (SyMRI) in evaluating the histological grade of BCa. Study type Prospective. Subjects Sixty patients (48 men and 12 women; mean age, 65 ± 11 years) with pathologically confirmed BCa (33 with high-grade BCa and 27 with low-grade BCa) were enrolled. Field strength/sequence Diffusion-weighted imaging (DWI) acquired by a single-shot echo-planar sequence and SyMRI acquired by a multidynamic multiecho (MDME) sequence at 3.0 T. Assessment Preoperative quantitative longitudinal relaxation time (T1 ), transverse relaxation time (T2 ), proton density (PD), and apparent diffusion coefficient (ADC) values of BCa were independently measured by two radiologists. Statistical tests Interclass correlation coefficient (ICC), independent sample t-test, Mann-Whitney U test, Delong test, and receiver operating characteristic curve (ROC) analysis were used. Results Significant differences were found in the mean of all the T1 , T2 , PD, and ADC values between high- and low-grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T1 , and T2 values were 0.755, 0.740, and 0.723, respectively. Data conclusion SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI-derived parameters was inferior to the ADC value. Levels of evidence 2. Technical efficacy stage 2.

Introduction This study compared treatment persistence and adherence among psoriatic arthritis (PsA) patients in the US who initiated an interleukin-12/23 inhibitor (IL-12/23i) versus those who initiated tumor necrosis factor inhibitors (TNFis), targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), or interleukin-17 inhibitors (IL-17is). Methods Adults diagnosed with PsA with ≥ 1 claim for a targeted immune modulator were selected from the IBM MarketScan® Commercial and Medicare Supplemental databases (October 1, 2013–October 31, 2018). The date of the first claim was the index date. Patients had continuous health plan enrollment for ≥ 12 months pre-index and ≥ 12-month post-index period. Pairwise propensity score matching with nearest-neighbor technique was performed. Persistence duration, discontinuation rate, and the proportion of days covered (PDC) were evaluated in biologic/tsDMARD naïve patients who initiated TNFis, IL-17is, tsDMARDs, or IL-12/23i (reference group). Results There were 238 matched patient pairs for TNFi versus IL-12/23i, 238 pairs for tsDMARD versus IL-12/23i, and 189 pairs for IL-17is versus IL-12/23i. Duration of persistence was longer for the IL-12/23i cohort than for the TNFi (269 vs. 215 days, p

Hypothyroidism is a systemic metabolic deficiency syndrome caused by a deficiency in thyroid hormone or a decrease in the action of thyroid hormones. It has a high incidence among women of child-bearing age, and pregnant women with hypothyroidism may have a higher risk of birth defects.To explore the specific biological mechanism affecting the occurrence of hypothyroidism.This study determined key molecules by comparing and analyzing the difference in methylation levels between pre-pregnancy women and normal controls using the Illumina Infinium MethylationEPIC BeadChip.3493 Differential methylation positions (DMPs) related genes and 47 differentially methylated regions (DMRs) related genes were found between the Hypothyroidism group and the control group. Among them, miR-21 has been found to be closely related to thyroid hormone regulation. The results of enrichment analysis showed that the DMPs or DMRs-related genes are both significantly enriched in human T-cell leukemia virus 1 infection, osteoclast differentiation and sphingolipid signaling pathway, which were also closely related to the occurrence and development of hypothyroidism. In addition, the combined analysis of CNVs and DMRs showed that significant differences occurred near the regions of 16 M bp in chromosome 1 between the two groups, and the genes involved in these regions included NDUFS2, FCER1G and SHC1.This work screened molecular markers and key signaling pathways that are involved in the development of hypothyroidism in pre-pregnancy women, which may provide new targets for the research and diagnosis of hypothyroidism in the future.

To evaluate the diagnostic accuracy of preoperative contrast-enhanced ultrasound (CEUS) to detect extracapsular extension (ECE) and identify the relationship between ECE and nodule enhancement patterns in patients with papillary thyroid cancer (PTC). Patients with suspected thyroid cancer underwent ultrasound (US) and CEUS examinations. The US and CEUS features of the PTC nodules and thyroid capsule were recorded and classified individually. The accuracy of US and CEUS in detecting ECE was compared individually, and its relationship with various tumour enhancement patterns was analysed. The presence or absence of ECE and cervical lymph node metastasis (LNM) was confirmed pathologically. The final dataset included 119 patients with 124 PTC nodules. Seventy-two (60.5%) of these patients with PTC had no ECE (including 38 patients with single capsule invasion), while the remaining 52 had ECE. A significant difference was found in nodules with non-capsule invasion, single capsule invasion, and ECE between the cervical LNM and non-LNM groups (p < 0.01). Receiver operating characteristic curve analysis demonstrated that area under the curve (AUC) of ECE for cervical LNM was higher than that of capsule invasion (71.9% vs. 49.6%). Moreover, the CEUS images acquired to detect ECE showed higher AUC values than those of US images (79.4% vs. 65.8%) (p = 0.02). Among the PTC nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%). Compared with conventional US, CEUS is a more valuable and non-invasive imaging modality to detect ECE. • Single capsular invasion was a poor predictor of cervical lymph node metastasis, while extracapsular extension assessments were clinically significant for predicting cervical lymph node metastasis. • CEUS is better than conventional US in detecting extracapsular extension in papillary thyroid carcinoma (AUC: 79.4% vs. 65.8%) (p = 0.02). • Among the thyroid papillary carcinoma nodules with differential enhancement, hyper-enhanced nodules had the highest incidence of single capsule invasion (41.9%), while hypo-enhanced ones had a higher incidence of ECE (47.4%).

To investigate the therapeutic mechanism of action of transplanted stem cells and develop exosome-based nanotherapeutics for ischemic stroke, we assessed the effect of exosomes (Exos) produced by human umbilical cord mesenchymal stem cells (hUMSCs) on microglia-mediated neuroinflammation after ischemic stroke. Our results found that injected hUMSC-Exos were able to access the site of ischemic damage and could be internalized by cells both in vivo and in vitro. In vitro, treatment with hUMSC-Exos attenuated microglia-mediated inflammation after oxygen-glucose deprivation (OGD). In vivo results demonstrated that treatment with hUMSC-Exos significantly reduced infarct volume, attenuated behavioral deficits, and ameliorated microglia activation, as measured three days post-transient brain ischemia. Furthermore, miR-146a-5p knockdown (miR-146a-5p k/d Exos) partially reversed the neuroprotective effect of hUMSC-Exos. Our mechanistic study demonstrated that miR-146a-5p in hUMSC-Exos reduces microglial-mediated neuroinflammatory response through IRAK1/TRAF6 pathway. We conclude that miR-146a-5p derived from hUMSC-Exos can attenuate microglia-mediated neuroinflammation and consequent neural deficits following ischemic stroke. These results elucidate a potential therapeutic mechanism of action of mesenchymal stem cells and provide evidence that hUMSC-Exos represent a potential cell-free therapeutic option for ischemic stroke.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Dangerous driving, e.g., using mobile phone while driving, can result in serious traffic problem and threat to safely. To efficiently alleviate such problem, in this paper, we design a intelligent monitoring system to detect the dangerous behavior in driving. The monitoring system is combined by camera, terminal server, target detection algorithm and voice reminder. Furthermore, we applied an efficiently deep learning model, namely mobilenet combined with single shot multi-box detector (mobilenet-SSD), to identify the behavior of driver. To evaluate the performance of proposed system, we construct a dangerous driving dataset which consists of 6796 images. The experimental results show that the proposed system can achieve accuracy of 99% in 100 testing images. It can be used for real-time monitoring of the driver’s status.

To investigate the clinicopathological and molecular features of colorectal cancer (CRC) with synchronous adenoma and to describe features of synchronous adenomas in CRC patients.Single-centre retrospective cohort of 180 patients were included. The clinicopathological and endoscopic data were collected. The expression mismatch repair (MMR) proteins were detected by immunohistochemistry. The determination of microsatellite instability (MSI) was performed by multiple fluorescence PCR, and the mutations of genes were detected by real-time PCR.Among all cases, 49 were diagnosed as CRC with synchronous adenoma, and 131 were diagnosed as solitary CRC. Some of the differences between the groups are: higher incidence was found in male (71.4 vs. 52.6%,Gender, a habit of drinking and other neoplastic diseases are risk factors for the development of a synchronous adenoma. With a low rate of BRAF mutations, the responses to monoclonal antibody and prognosis of patients with synchronous adenomas may be better than that of solitary CRC.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.

The platysma skin flap was used for laryngeal reconstruction after vertical partial laryngectomy to improve the postoperative voice quality of patients with T2 and T3 glottic laryngeal carcinoma. Sixty-nine patients with unilateral T2 and T3 glottic laryngeal carcinoma were included. Forty-six patients received vertical partial laryngectomy, and a platysma skin flap was used for laryngeal reconstruction. The other 23 patients underwent transoral laser microsurgery. Subjective and objective examinations were performed to evaluate laryngeal morphology after the surgery. Acceptable voice quality was achieved for 46 patients who underwent vertical partial laryngectomy. Flap vibrational waves occurred in 19 cases (41.3%). The platysma skin flap is an ideal tissue for the reconstruction of articulation structure in open surgery of T2 and T3 unilateral glottic laryngeal carcinoma.

Objectives: To assess long-term (2-year) biologic treatment patterns of psoriatic arthritis (PsA) patients who initiated adalimumab, certolizumab pegol, etanercept, golimumab, or ustekinumab.Method...

Aim and Objective: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. Materials and Methods: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. Results: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. Conclusions: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Although there has been increasing interest in aesthetical approaches for treating patients with papillary thyroid carcinoma (PTC), there have been no studies comparing the safety and effectiveness of gasless endoscopic selective lateral neck dissection (SLND) via the anterior chest approach (ACA) with that of conventional open surgery (OPEN) for papillary thyroid carcinoma. A total of 91 patients with PTC who underwent either gasless endoscopic thyroidectomy, central compartment neck dissection and SLND via the ACA or conventional open surgery between Nov. 2008 to Dec. 2018 were included. Primary outcomes and demographic data were compared between the two groups. Thirty-one patients were in the ACA group and 60 were in the OPEN group. The ACA group was younger and had a longer operative time but less intraoperative hemorrhage (P

Acute kidney injury (AKI) is a common clinical complication associated with high mortality in patients. Immune cells and cytokines have recently been described to play essential roles in AKI pathogenesis. Plasmacytoid dendritic cells (pDCs) are a unique DC subset that specializes in type I interferon (IFN) production. Here, we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α. Deletion of pDCs using DTR(BDCA2) transgenic (Tg) mice suppressed cisplatin-induced AKI, accompanied by marked reductions in proinflammatory cytokine production, immune cell infiltration and apoptosis in the kidney. In contrast, adoptive transfer of pDCs during AKI exacerbated kidney damage. We further identified IFN-α as the key factor that mediated the functions of pDCs during AKI, as IFN-α neutralization significantly attenuated kidney injury. Furthermore, IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells (TECs) in vitro. In addition, our data demonstrated that apoptotic TECs induced the activation of pDCs, which was inhibited in the presence of an apoptosis inhibitor. Furthermore, similar deleterious effects of pDCs were observed in an ischemia reperfusion (IR)-induced AKI model. Clinically, increased expression of IFN-α in kidney biopsies was observed in kidney transplants with AKI. Taken together, the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.

Despite the increasing number of inflammatory bowel disease (IBD) patients using traditional Chinese medicine (TCM), relatively few studies have examined their experiences with TCM in the Chinese healthcare context. The aim of this study was to explore these experiences from the perspective of IBD patients. Adopting a qualitative descriptive method, IBD patients from several comprehensive hospitals in Hangzhou, Zhejiang were recruited through purposive sampling. Data were collected using semistructured interviews and analyzed by a conventional content analysis method. The results are presented thematically. Fourteen IBD patients participated in the study. They often used TCM, such as Chinese herbal medicine, retention enemas of Chinese medicine, and acupuncture, as a complementary therapy instead of as an alternative to conventional therapies. Three themes emerged from the analysis: triggers for initiating TCM, the experienced efficacies of TCM, and disturbances caused by TCM use. The IBD patients initiate TCM treatment due to the unsatisfactory effects of conventional therapies and TCM culture. However, the efficacies of TCM are subjective and slow acting and vary across individuals. There are communication gaps between physicians and patients concerning TCM. Thus, healthcare professionals are encouraged to gain more knowledge on these therapies and employ a participatory decision-making style based on this understanding.

Background To explore the therapeutic effect of topical 5-Aminolevulinic Acid photodynamic therapy (ALA-PDT) on laryngeal papillomatosis (LP) treatment. Methods 13 patients with LP underwent topical ALA-PDT after tumor resection (CO2laser or/and microdebrider resection). All patients were irradiated 3–4 times. After ALA-PDT treatment, the laryngoscopic examination was performed every 1–2 months to observe the therapeutic effect. Results All 13 patients were followed up for more than 1 year. Eleven cases (84.6%) showed no recurrence; two cases (15.4%) had relapses. One child developed III° inspiratory dyspnea caused by laryngeal mucosal edema and need endotracheal intubation again. Four patients had adhesion of the anterior commissure of the vocal cord. The detection rate of HPV infections was 76.9% and two patients had multiple HPV subtype co-infection. Conclusions The preliminary effect of topical ALA-PDT significantly reduces recurrence and improves the cure rate of LP. Further research on this treatment is still required.

Objective: To examine the incremental mental health care resource utilization (MHRU) and barriers to receiving mental health services among adults with a major depressive episode (MDE) and suicidal ideation or behavior with intent. Methods: Data from adult participants in the 2017 National Survey on Drug Use and Health were used to identify 3 cohorts: MDE (determined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) with suicidal ideation or behavior with intent (MDSI), MDE, and non-MDE. MHRU and barriers to receiving mental health services were compared among cohorts using logistic regression models. Results: The MDSI cohort had significantly higher odds (adjusted odds ratio [95% confidence interval]) of receiving mental health-related inpatient care, outpatient care, prescription medications, and any treatment versus the MDE cohort (10.2 [7.1-14.6], 2.4 [1.7-3.4], 2.4 [1.8-3.3], and 2.6 [1.8-3.7], respectively) and the non-MDE cohort (40.3 [27.3-59.5], 20.0 [14.5-27.7], 17.2 [12.9-22.9], and 19.6 [14.1-27.1], respectively). Compared to the MDE cohort, the MDSI cohort was significantly more likely to report barriers to receiving mental health services (2.6 [2.0-3.4]), with the largest differences between cohorts related to fear of negative impact (3.9 [2.8-5.4]). Additionally, 30.6% of the MDSI cohort and 47.0% of the MDE cohort did not receive any mental health treatment in the past year. Conclusions: Although respondents in the MDSI cohort reported substantially higher MHRU across all categories, they also reported greater barriers to receiving care than those in the MDE cohort. This study documents the extensive burden and unmet need in the MDSI population.

Thalassemia is one of the most common genetic diseases in southern China. Accurate population frequency data regarding the occurrence and distribution of thalassemia is important for designing appropriate prevention strategies of thalassemia.The aim of this study is to reveal the prevalence and the mutation spectrum of thalassemia in neonates in the Wuhan region of central China.About 3796 neonates in Wuhan area of China were analyzed by hematological and genetic analysis.About 2174 subjects were genetically diagnosed as thalassemia carriers or patients, including 1415 cases of α-thalassemia (65.89%), 731 cases of β-thalassemia (33.62%), and 28 cases of α-composite β-thalassemia (1.29%). A total of 11 genotypes and 6 gene mutations were identified in α-thalassemia anomalies, with -There was high heterogeneity and extensive spectrum of thalassemia in the neonates in Wuhan populations. The findings will be useful for genetic counseling and prenatal diagnosis of thalassemia in the Wuhan region.

Brain metastasis (BM) is associated with poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to identify microRNAs (miRNAs) that could serve as biomarkers to differentiate NSCLC patients with and without BM. Logistic regression was conducted with 122 NSCLC patients (60 without BM, 62 with BM) to assess the association between miRNAs and BM. We confirmed several risk factors for BM and revealed that serum miR-330-3p levels are higher in NSCLC patients with BM than that without BM. Overexpression of miR-330-3p promoted proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of NSCLC cells in vitro and NSCLC tumorigenesis in vivo. Knocking down miR-330-3p suppressed this metastatic phenotype. We identified putative miR-330-3p target genes by comparing mRNA microarray analysis data from A549 cells after miR-330-3p knockdown with candidate miR-330-3p target genes predicted by public bioinformatic tools and luciferase reporter assays. We found that GRIA3 is a target of miR-330-3p and that miR-330-3p stimulates EMT progress by mediating GRIA3-TGF-β1 interaction. Our results provide novel insight into the role of miR-330-3p in NSCLC metastasis, and suggest miR-330-3p may be a useful biomarker for identifying NSCLC with metastatic potential.

Background To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC., Similar imaging features such as regional enlargement of the pancreas and delayed enhancement became a big challenge to differentiate focal‐type autoimmune pancreatitis (fAIP) from PDAC. In this study, we found that the pancreatic parenchyma of fAIP presented severe inflammation. Moreover, the mean relative computed tomography values of the pancreatic parenchyma were lower in fAIP than that in PDAC in all phases.

Objective: To describe the prevalence and costs of anxiety and depression among moderate-to-severe psoriasis (PsO) patients in a commercially-insured US population. Methods: The IBM MarketScan Commercial database was used to select adults with moderate-to-severe PsO (≥1 PsO diagnosis and ≥1 systemic or biologic medication) within each calendar year from 2014 to 2016. Adults with no diagnosis of PsO or similar disorders were randomly selected (2014–2016) and matched 1:1 to PsO patients to compare the prevalence of anxiety and depression each year. Moderate-to-severe PsO patients identified in 2014 with continuous enrollment through 2015 were stratified into those with treated anxiety and/or depression (≥1 anxiety or depression diagnosis plus any anxiolytics, antidepressants, or antipsychotics within 30 days) vs those without anxiety/depression, and then matched 1:1 to determine the incremental burden of treated anxiety/depression among PsO patients. All-cause and PsO-related healthcare costs were compared between the matched cohorts using generalized linear models. Results: In total, 69,644 matched PsO and non-PsO patients were identified in 2014, 61,478 in 2015, and 66,880 in 2016. The prevalence of anxiety/depression among PsO patients increased more than for matched controls, from 18.2% vs 12.2% in 2014 (p p p p p p Conclusions: The prevalence of psychiatric disorders is higher among PsO patients than the general population, and the incremental burden of treated anxiety/depression is substantial. Further research is needed, but PsO treatments that improve psychiatric symptoms such as anxiety/depression may benefit patients and reduce their economic burden.

An early diagnosis of interstitial lung disease (ILD) is important for guiding treatments of rheumatoid arthritis (RA)-associated ILD (RA-ILD) in clinical settings. The non-canonical Wnt signaling representative ligand Wnt5a was recently found to involve in idiopathic pulmonary fibrosis (IPF) and pathogenesis of RA. The goal of this study was to examine the clinical relevance of Wnt5a in RA-ILD. In this report, the clinical relevance of plasma Wnt5a protein was evaluated in 40 RA-ILD patients and 41 non-ILD RA cohorts. The results showed an elevated Wnt5a protein in plasmas of RA-ILD patients compared with non-ILD RA patients (p 0.01), which was positively correlated with the plasma level of rheumatoid factor (RF). Of note, more abundant Wnt5a was also found in patients with usual interstitial pneumonia (UIP) than those with nonspecific interstitial pneumonia (NSIP) and other ILD patterns. More importantly, the disease severity was correlated with the circulating Wnt5a as ascertained by high-resolution computed tomography (HRCT)-UIP scores. The multiple-factor non-conditional logistic regression analysis further revealed that the age, RA duration, smoking and plasma Wnt5a were risk factors with clinical significance for RA-ILD. Interestingly, more Wnt5a-positive patients were identified in RA-ILD smokers relative to RA-ILD never-smokers, and longer smoking duration was strongly correlated with Wnt5a in RA-ILD patients. In consistence, ROC curve also suggested that the Wnt5a was a potential candidate biomarker for identifying patients with RA-UIP. These results demonstrate that the circulating Wnt5a may be a risk factor and potential biomarker for identifying UIP and accessing the severity and progression of ILD in RA patients.

Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia. Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12 months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP. Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p

Bone marrow-derived mesenchymal stem cells (BMSCs) exhibit potential regenerative effects on the injured brain. However, these effects are constrained by their limited ability to migrate to the injured site. Oncostatin M (OSM) has been shown to affect the proliferation and migration of mesenchymal stem cells. Therefore, in the present study, we explored whether OSM improves BMSC migration and secretion of growth factors and cytokines in a rat middle cerebral artery occlusion (MCAO) stroke model. The effect of OSM on the proliferation and apoptosis of rat BMSCs was first assessed in vitro, and the gene and secretion levels of factors related to cell nutrition and migration, such as SDF-1 and VEGF, were detected. To further explore underlying pathways triggered by OSM, BMSCs were treated with OSM in the presence or absence of inhibitors of the STAT3 and ERK pathways. Effects of OSM on SDF-1 expression in astrocytes and BMSC migration were also evaluated. In the rat MCAO model, OSM secretion levels were detected in the brain for up to 72 h after model establishment. Ventricle injection of OSM alone or OSM combined with caudal vein graft of BMSCs was then performed in MCAO stroke rats. After 72 h, production of SDF-1 and grafted BMSCs was detected in the lesion areas of the brain, and the nerve function score was evaluated. We found that the production of OSM continually increased in the brains of MCAO rats from 12 h to 72 h. OSM significantly upregulated SDF-1 in BMSCs via the STAT3 and ERK pathways and significantly promoted the expression of VEGF and MMP-2. OSM also promoted the secretion of SDF-1 in astrocytes through the STAT3 and ERK pathways to in turn enhance BMSC migration. Combination treatment with OSM and BMSCs in MCAO rats increased the migration efficiency of BMSCs in the brain, which significantly improved neurofunctional recovery while reducing the expression of inflammatory mediators and promoting the secretion of nutrition factors. Overall, these results show that OSM is highly expressed in the brains of MCAO stroke rats and can upregulate SDF-1 to promote BMSC migration. Thus, combination treatment with OSM and BMSCs improves the graft efficiency of BMSCs and neurofunctional recovery.

BACKGROUND In traditional Chinese medicine, acupuncture has been used to treat angina due to coronary artery disease (CAD). The aim of this systematic review of the literature and meta-analysis was to identify published randomized controlled trials (RCTs) that quantified the effectiveness of adjunctive acupuncture treatment in patients with angina due to CAD who were also treated with Western or Chinese medicine. MATERIAL AND METHODS A systematic review of the literature included a search of the PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) databases, from their inception to September 2018. Published findings from RCTs were included that investigated the effectiveness of acupuncture as an adjunctive treatment for angina due to CAD in combination with Western or traditional Chinese medicine. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the random-effects model to determine the outcomes of markedly and moderately effective rates for the use of acupuncture. RESULTS Twenty-four published RCTs were identified that included 1,916 patients with CAD. Patients who received adjunctive acupuncture treatment had a significantly increased markedly effective rate. However, the moderately effective rate between adjunctive acupuncture combined with standard treatment for angina and standard treatment alone was not statistically significant. Sensitivity analysis showed that the pooled results for the markedly and moderately effective rates were robust. Subgroup analysis in most subsets supported the main findings. CONCLUSIONS Meta-analysis supported a positive treatment effect for the use of acupuncture when used as adjunctive therapy in patients with angina due to CAD.

BACKGROUND This study assessed the effects and underlying molecular mechanisms of ß-asarone on ischemic stroke model rats. MATERIAL AND METHODS Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) in rats. Before and after modeling, cognitive function was evaluated via fear conditioning test and neurological deficit was determined via Longa and Bederson scores. Following treatment with ß-asarone or nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor for 20 consecutive days, the cerebral infarction was detected via TTC staining and Cresyl Violet staining in brain tissues. TUNEL staining and western blot analysis for apoptosis-related proteins were performed to assess the apoptosis of neurons. Nrf2-antioxidant response elements (ARE) pathway-related proteins were examined by RT-qPCR or western blot. RESULTS The cognitive and neurological function was defective in MCAO rats. The infarction volumes and the apoptosis of cortical neurons were significantly increased in brain tissues of model rats, which were ameliorated after treatment with ß-asarone. Meanwhile, the increase in pro-apoptotic proteins and decrease in anti-apoptotic proteins were found in brain tissues of model rats, which were markedly ameliorated by ß-asarone treatment. However, Nrf2 inhibitor worsened the cerebral infarction and the apoptosis of neurons. Western blot results showed that ß-asarone treatment activated the Nrf2-ARE pathway-related proteins in model rats, which was inhibited by Nrf2 inhibitor. CONCLUSIONS Our findings suggest that ß-asarone treatment ameliorated the cerebral infarction in MCAO rats, which could be related to activation of the Nrf2-ARE pathway.

Background Airway management, including noninvasive endotracheal intubation or invasive tracheostomy, is an essential treatment strategy for patients with deep neck space abscess (DNSA) to reverse acute hypoxia, which aids in avoiding acute cerebral hypoxia and cardiac arrest. This study aimed to develop and validate a novel risk score to predict the need for airway management in patients with DNSA. Methods Patients with DNSA admitted to 9 hospitals in Guangdong Province between January 1, 2015, and December 31, 2020, were included. The cohort was divided into the training and validation cohorts. The risk score was developed using the least absolute shrinkage and selection operator (LASSO) and logistic regression models in the training cohort. The external validity and diagnostic ability were assessed in the validation cohort. Results A total of 440 DNSA patients were included, of which 363 (60 required airway management) entered into the training cohort and 77 (13 required airway management) entered into the validation cohort. The risk score included 7 independent predictors (p < 0.05): multispace involvement (odd ratio [OR] 6.42, 95% confidence interval [CI] 1.79–23.07, p < 0.001), gas formation (OR 4.95, 95% CI 2.04–12.00, p < 0.001), dyspnea (OR 10.35, 95% CI 3.47–30.89, p < 0.001), primary region of infection, neutrophil percentage (OR 1.10, 95% CI 1.02–1.18, p = 0.015), platelet count to lymphocyte count ratio (OR 1.01, 95% CI 1.00–1.01, p = 0.010), and albumin level (OR 0.86, 95% CI 0.80–0.92, p < 0.001). Internal validation showed good discrimination, with an area under the curve (AUC) of 0.951 (95% CI 0.924–0.971), and good calibration (Hosmer–Lemeshow [HL] test, p = 0.821). Application of the clinical risk score in the validation cohort also revealed good discrimination (AUC 0.947, 95% CI 0.871–0.985) and calibration (HL test, p = 0.618). Decision curve analyses in both cohorts demonstrated that patients could benefit from this risk score. The score has been transformed into an online calculator that is freely available to the public. Conclusions The risk score may help predict a patient’s risk of requiring airway management, thus advancing patient safety and supporting appropriate treatment.

Si-Wen Tan,1,2,* Guo-Qian Cai,3,* Qiu-Yu Li,1,* Yu Guo,3 Yi-Cong Pan,1 Li-Juan Zhang,1 Qian-Min Ge,1 Hui-Ye Shu,1 Xian-Jun Zeng,3 Yi Shao1 1Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yi ShaoDepartment of Ophthalmology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88692520Email freebee99@163.comXian-Jun ZengDepartment of Radiology, The First Affiliated Hospital of Nanchang University, No. 17, YongWaiZheng Street, DongHu District, Nanchang, 330006, Jiangxi, People’s Republic of ChinaTel/Fax +86 791-88694639Email 375135747@qq.comPurpose: Previous research suggests that diabetic optic neuropathy (DON) can cause marked anatomical and functional variations in the brain, but to date altered functional synchronization between two functional hemispheres remains uncharacterized in DON patients. Voxel mirrored homotopic connectivity (VMHC) is a voxel-based method to evaluate the synchronism between two mirrored hemispheric by determining the functional connectivity between each voxel in one hemisphere and its counterpart. In this study, we aim to assess abnormal changes in interhemispheric functional connectivity in DON patients via the VMHC method.Methods: The study included 28 adult DON patients (12 male, 16 female) and 28 healthy controls (12 male, 16 female) who were closely matched for sex and age. Participants were examined using resting-state functional magnetic resonance imaging. The VMHC method was applied to investigate the abnormal state in bilateral hemispheres in DON patients and the same regions in healthy controls, as well as the receiver operating characteristic (ROC) curves were used to evaluate characteristics. Associations between altered VMHC values in distinct cerebral regions and clinical features were assessed via correlational analysis.Results: Markedly lower VMHC values were evident in the right temporal inferior, the left temporal inferior, the right mid-cingulum, the left mid-cingulum, the right supplementary motor region, and the left supplementary motor region in DON patients compared with healthy controls. ROC curve analysis suggested that the application of VMHC is reliable for the diagnosis of DON.Conclusion: Anomalous interhemispheric functional connectivity in specific brain areas caused by DON may indicate neuropathologic mechanisms of vision loss and blurry vision in patients with DON.Keywords: diabetes, diabetic optic neuropathy, magnetic resonance imaging, resting-state functional MRI

Background To evaluate functional connection density (FCD) in patients with diabetic optic neuropathy (DON) using the resting functional connectivity (FC) method, and to determine the abnormal areas of brain activity. Methods Patients with DON (n=22; 10 male, 12 female) and healthy controls (HCs; n=22; 10 male, 12 female) were included in the study. The basic characteristics of the groups were matched. Functional magnetic resonance imaging (fMRI) was conducted with participants at rest, and long- and short-range FCD (long FCD and IFCD, respectively) were measured. Receiver operating characteristic (ROC) curve analysis was also conducted to determine whether DON and HC participants could be distinguished using fMRI indicators. Results Compared with HCs, the long FCD values of the left lingual gyrus, right lingual gyrus, right fusiform gyrus, and medial and lateral cingulate gyri were decreased in patients with DON. Further, the IFCD values of the left superior temporal gyrus, left inferior temporal gyrus, right inferior temporal gyrus, left cerebellar area 8, and right cerebellar Crus2 area were higher in patients with DON than in the HCs. Conclusions DON is associated with abnormal spontaneous brain activity. Our findings contribute to elucidating the mechanisms underlying the neuropathology of DON, and provide direction for further clinical research.

The discriminative spatial patterns (DSP) approach is a classical and effective feature extraction technique for single-trial EEG classification in movement task. However, it utilizes only the spatial information of EEG signals. On the other hand, the temporal information plays an important role in EEG sequences with high temporal resolution. In this paper, we propose a novel method which uses DSP to simultaneously filter the temporal and spatial dimensions to extract spatiotemporal information. Experimental results of single-trial EEG classification demonstrate that the proposed 2DDSP method obtains better classification accuracy than DSP, while the dimension of the feature matrix produced by 2DDSP is less than that of DSP.

The discriminative spatial patterns (DSP) algorithm is a classical and effective feature extraction technique for decoding of voluntary finger premovements from electroencephalography (EEG). As a purely data-driven subspace learning algorithm, DSP essentially is a spatial-domain filter and does not make full use of the information in frequency domain. The paper presents multilinear discriminative spatial patterns (MDSP) to derive multiple interrelated lower dimensional discriminative subspaces of low frequency movement-related cortical potential (MRCP). Experimental results on two finger movement tasks’ EEG datasets demonstrate the effectiveness of the proposed MDSP method.

Background: Oncolytic virotherapy is a new and safe therapeutic strategy for cancer treatment. In our previous study, a new type of oncolytic herpes simplex virus type 2 (oHSV2) was constructed. Following the completion of a preclinical study, oHSV2 has now entered into clinical trials for the treatment of melanoma and other solid tumors (NCT03866525). Oncolytic viruses (OVs) are generally able to directly destroy tumor cells and stimulate the immune system to fight tumors. Natural killer (NK) cells are important components of the innate immune system and critical players against tumor cells. But the detailed interactions between oncolytic viruses and NK cells and these interaction effects on the antitumor immune response remain to be elucidated. In particular, the functions of activating surface receptors and checkpoint inhibitors on oHSV2-treated NK cells and tumor cells are still unknown. Methods: UV-inactivated oncolytic herpes simplex virus type 2 (UV-oHSV2) was used to stimulate immune cells (especially NK cells), and the NK cell-induced antitumor effects and their mechanisms were further investigated. In addition, the effect of UV-oHSV2 stimulation with or without checkpoint (NKG2A/HLA-E) antibody treatment on NK cell antitumor activity was explored in vitro and in vivo. Findings: We found that UV-oHSV2 potently activates human peripheral blood mononuclear cells, leading to increased antitumor activity in vitro and in vivo. Further investigation indicated that UV-oHSV2-stimulated NK cells release IFN-γ via Toll-like receptor 2 (TLR2)/NF-κB signaling pathway and exert antitumor activity via TLR2. We found for the first time that the expression of a pair of checkpoint molecules, NKG2A (on NK cells) and HLA-E (on tumor cells), is upregulated by UV-oHSV2 stimulation. Anti-NKG2A and anti-HLA-E treatment could further enhance the antitumor effects of UV-oHSV2-stimulated NK92 cells in vitro and in vivo. Interpretation: Our results indicate that UV-oHSV2-stimulated NK cells have enhanced antitumor activity. The activating surface receptor (TLR2), checkpoint inhibitor (NKG2A) on NK cells and checkpoint inhibitor (HLA-E) on tumor cells were relative to UV-oHSV2-stimulated NK cells antitumor effects. Funding: National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2018ZX09733002). Declaration of Interests: Z. Fang is employed by Wuhan Binhui Biopharmaceutical Co., Ltd. He would like to state clearly that there are no commercial conflicts with this work. There are no patents, products in development or marketed products to declare. The interpretation of the results was completely independent from any company's opinion. This affiliation does not alter the authors’ adherence to all policies on sharing data and materials. The authors declare no potential conflict of interest. Ethics Approval Statement: Peripheral blood from healthy donors and lymphocytes from patient pleural effusion were collected according to the protocols (2018-059-007) approved by the Ethics Committee of the Hubei Cancer hospital. All animal experiments were conducted under protocol approved by the Hubei Province, PR China, Biological Studies Animal Care and Use Committee (HBUT No. 2018010).

Purpose: The aim of this study was to assess the effect of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and understand its underlying mechanisms. Methods: Mice were separated into four different groups at random, including LPS, LPS+ PHI (5 mg/kg), LPS + PHI (50 mg/kg) and control group. The two LPS + PHI groups were intraperitoneally administered with PHI after LPS intratracheal administered for 1 h. Subsequently, the lung tissues of different groups were collected and evaluated by H&E staining and W/D (W/D) ratio. The inflammatory cytokines in BALF or lung tissue were also assessed. Western blot assay was applied to examine the expressions of TLR4, MyD88, and NF-κB. Results: The ameliorated pathological changes and lung W/D ratio demonstrated that PHI dramatically suppressed the lung injury levels. PHI strikingly reduced the number of inflammatory cell counts and total protein concentration in BALF. In addition, PHI attenuated expression of IL-1β and TNF-α in BALF and lung tissue. Furthermore, it was confirmed that PHI alleviated LPS-induced ALI via TLR4/MyD88/NF-κB pathway. Conclusions: Together the above results show that PHI attenuates LPS-induced ALI via inactivation of TLR4/MyD88/NF-κB pathway in newborn mice.

As a multichannel spatial filtering technique, common spatial patterns (CSP) have been successfully applied in brain-computer interfaces (BCI) community based on electroencephalogram (EEG). However, it is sensitive to outliers because of the employment of the L2-norm in its formulation. It is beneficial to perform robust modelling for CSP. In this paper, we propose a robust framework, called CSP-Lp/q, by formulating the variances of two EEG classes with Lp- and Lq-norms ( 0 < p and q < 2 ) separately. The method CSP-Lp/q with mixed Lp- and Lq-norms takes the class-wise difference into account in formulating the sample dispersion. We develop an iterative algorithm to optimize the objective function of CSP-Lp/q and show its monotonity theoretically. The superiority of the proposed CSP-Lp/q technique is experimentally demonstrated on three real EEG datasets of BCI competitions.

OBJECTIVE. The purpose of our study was to retrospectively characterize the CT and MRI features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). MATERIALS AND METHODS. Eleven patients (10 women and one man; age range, 30-63 years) with 11 pathologically proven LELCCs were enrolled retrospectively from April 2016 to December 2018. Triphasic enhanced images were obtained of all patients: MR images of five patients, CT images of five patients, and both CT and MR images of one patient. The clinical data and CT and MRI findings were reviewed. RESULTS. All LELCC cases were associated with Epstein-Barr virus (EBV) infection. Eight of the 11 patients had hepatitis B virus (HBV) infection. The tumor diameter ranged from 1.1 to 8.7 cm. All tumors were well defined with a smooth or lobulated margin. A cystic area was noted in two of the 11 tumors. After the administration of contrast material, the tumors showed homogeneous (n = 7) or heterogeneous (n = 4) hypervascular arterial enhancement and gradual washout, delayed central scar or irregular enhancement (n = 9), delayed circular thin or incomplete pseudocapsule enhancement (n = 7), and homogeneous hypointensity in the hepatobiliary phase (n = 2). No cirrhosis, focal dilatation of intrahepatic ducts, or satellite nodules were detected. Lymphadenopathy were detected in four patients, appearing as hypervascular enhancement and no necrosis (even in multiple nodes > 3 cm) or as moderate peripheral enhancement and necrosis. CONCLUSION. A liver mass in a middle-aged woman with EBV and HBV infection that appears on CT and MRI to have a well-defined boundary and a combination of hypervascularity, washout, delayed intratumoral enhancement, or pseudocapsule enhancement may suggest an imaging diagnosis of primary LELCC. More cases are needed to better understand this disease.

Objectives This study aimed to explore the dignity and related factors among older adults in long-term care facilities. Methods Cross-sectional data were obtained from a sample of 253 Chinese older adults dwelling in long-term care facilities. Dignity among older adults was measured using the Dignity Scale, and its potential correlates were explored using multiple linear regressions. Results Results showed that the total score of the Dignity Scale is 151.95 ± 11.75. From high to low, the different factors of dignity among older adults in long-term care facilities were as follows: caring factors (4.83 ± 0.33), social factors (4.73 ± 0.41), psychological factors (4.66 ± 0.71), value factors (4.56 ± 0.53), autonomous factors (4.50 ± 0.57), and physical factors (4.38 ± 0.55). A higher score of the Dignity Scale was associated with higher economic status, fewer chronic diseases, less medication, better daily living ability and long-time lived in cities. Conclusion Older adults with low economic status, more chronic diseases, and poor daily living ability, taking more medications, or the previous residence in rural areas seem to be most at low-level dignity in long-term care facilities and thus require more attention than their peers.

Targeting the common molecular mechanism of type 2 diabetes mellitus and Alzheimer's disease (AD), including dysregulation of glucose metabolism, insulin resistance, and neuroinflammation, might be an efficient treatment strategy for AD. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous PPARγ agonist, has anti-inflammatory, insulin sensitizing and anti-diabetic effects. However, whether 15d-PGJ2 has beneficial effects on AD remains to be elucidated. In the present study, we found that intranasal administration of 15d-PGJ2 (300 ng/30 μL/day) for 3 months significantly inhibited Aβ plaques, suppressed neuroinflammation, and attenuated cognitive deficits in APP/PS1 transgenic mice. Interestingly, 15d-PGJ2 treatment could increase brain glucose uptake, as detected by 18F-FDG microPET imaging, and co-localization of GLUT4 and NeuN in the hippocampus of APP/PS1 mice. Furthermore, 15d-PGJ2 markedly increased the expression of PPARγ and PGC-1α, upregulated GLUT4, and decreased the phosphorylation of IRS-1 (Ser616) in the hippocampus of APP/PS1 mice. Importantly, co-administration of a PPARγ antagonist GW9662 abrogated these protective effects of 15d-PGJ2. Collectively, intranasal 15d-PGJ2 conferred protective effects against AD by activating PPARγ-dependent PGC-1α/GLUT4 signalling. The PPARγ agonist 15d-PGJ2 might be a potential therapeutic drug for AD.

Background Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was P P P = 0.12). Conclusion Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.

The sudden pandemic of SARS-Cov-2 (also known as novel coronavirus disease 2019, COVID-19) poses a severe threat to hundreds of millions of lives in the world. The complete cure of the virus largely relies on the immune system, which becomes particularly a challenge for the cancer subjects, whose immunity is generally compromised. However, in a constant evolving situation, the clinical data on the prevalence of SARS-Cov-2 for cancer patients is still limited. On top of a wide range of medical references and interim guidelines including CDC, NCI, ASCO, ESMO, NCCN, AACR, ESMO, and the National Health Commission of China, etc., we formed into a guideline based on our experience in our specialized cancer hospital in Wuhan, the originally endemic center of the virus. Furthermore, we formulated an expert consensus which was developed by all contributors from different disciplines after fully discussion based on our understanding and analysis of limited information of COVID-19. The consensus highlighted a multidisciplinary team diagnostic model with assessment of the balance between risks and benefits prior to treatment, individualizing satisfaction of patients’ medical needs, and acceptability in ethics and patients’ socio-economic conditions.

The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) contribute to an increased response rate, compared with chemotherapy, in patients with inhibitor-sensitive EGFR mutations. The present study evaluated the association between the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT), as well as serum carcinoembryonic antigen (CEA) levels and EGFR mutations prior to treatment, in patients with non-small cell lung cancer (NSCLC). Patients with histologically confirmed NSCLC (n=167), who underwent an 18F-FDG PET/CT scan, EGFR mutation analysis and a serum CEA test participated in the present study. Multivariate logistic regression analysis was used to analyze predictors of EGFR mutations. Receiver-operating characteristic (ROC) curve analysis was performed to determine the efficient cut-off value. Survival rate analysis was evaluated according to SUVmax and EGFR mutation status. A decreased SUVmax and an increased CEA level was observed in patients with EGFR-mutations, compared with patients with wild-type primary lesions and metastatic lymph nodes. The exon 19 EGFR mutation was associated with increased SUVmax, compared with the exon 21 L858R mutation. The ROC analysis indicated that an 18F-FDG PET/CT uptake SUVmax >11.5 may be a predictor of the wild-type EGFR genotype and increased CEA levels (CEA >9.4 ng/ml) were associated with EGFR mutations. Furthermore, patients with no smoking history, low SUVmax of the primary tumor, metastatic lymph nodes and a high CEA level were significantly associated with EGFR mutation status. The results of the present study indicated that patients with advanced NSCLC, particularly Chinese patients, with decreased SUVmax and increased CEA levels are associated with EGFR mutations, which may serve as predictors for the EGFR-TKI therapeutic response.

Purpose: The aim was to investigate the associations between maternal thyroid parameters within the normal ranges during early pregnancy and birth outcomes, and further to examine whether the associations were modified by gestational weight gain (GWG). Methods: Maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations within the normal ranges during early pregnancy were measured from 8,107 pregnant women in Wuhan, China. The associations between maternal thyroid parameters and birth outcomes (birth weight, birth length, and low birth weight) were analyzed using multivariable adjusted regression models, and effect modification by pre-pregnancy body mass index (BMI) category and GWG were further evaluated. Results: Maternal TSH and FT4 concentrations were negatively associated with birth weight, and the latter only occurred in normal weigh women with inadequate and excessive GWG, as well as in both underweight and overweight women with excessive GWG (e.g., β = -359.33 g, 95% CI: -700.95, -17.72 in underweight women with excessive GWG for per unit increase of FT4 concentrations). Moreover, maternal FT4 and FT3 concentrations were associated with increased risk for low birth weight, and the latter only occurred in normal weigh women with inadequate GWG (OR = 2.52, 95% CI: 1.00, 6.36 for per unit increase of FT3 concentrations). These associations still persist when maternal thyroid parameters were modeled as quintiles. Main conclusion: Maternal normal thyroid function during early pregnancy with excessive and inadequate GWG may adversely influence fetal growth.

Rationale and Objectives We aimed to assess the prevalence of significant computed tomographic(CT) manifestations and describe some notable features based on chest CT images, as well as the main clinical features of patients with coronavirus disease 2019(COVID-19). Materials and Methods A systematic literature search of PubMed, EMBASE, the Cochrane Library, and Web of Science was performed to identify studies assessing CT features, clinical, and laboratory results of COVID-19 patients. A single-arm meta-analysis was conducted to obtain the pooled prevalence and 95% confidence interval (95% CI). Results A total of 14 articles (including 1115 patients) based on chest CT images were retrieved. In the lesion patterns on chest CTs, we found that pure ground-glass opacities (GGO) (69%, 95% CI 58–80%), consolidation (47%, 35–60%) and “air bronchogram sign” (46%, 25–66%) were more common than the atypical lesion of “crazy-paving pattern” (15%, 8–22%). With regard to disease extent and involvement, 70% (95% CI 46–95%) of cases showed a location preference for the right lower lobe, 65% (58–73%) of patients presented with ≥3 lobes involvement, and meanwhile, 42% (32–53%) of patients had involvement of all five lobes, while 67% (55–78%) of patients showed a predominant peripheral distribution. An understanding of some important CT features might be helpful for medical surveillance and management. In terms of clinical features, muscle soreness (21%, 95% CI 15–26%) and diarrhea (7%, 4–10%) were minor symptoms compared to fever (80%, 74–87%) and cough (53%, 33–72%). Conclusion Chest CT manifestations in patients with COVID-19, as well as its main clinical characteristics, might be helpful in disease evolution and management.

Perioperative neurocognitive disorders (PND) are highly prevalent after surgery, especially in aged patients. PND results in long-term morbidity and mortality with unclear pathophysiologic mechanisms. As a key hallmark of PND, surgery-induced neuroinflammation resulted from the invading of exogenous tracers into the cerebral parenchyma, causing hippocampal neuroinflammation and cognitive impairment. IL-32, with different isoforms, played a significant regulatory role in various inflammatory diseases. Its prevalence in peripheral circulating blood was closely associated with the central nervous system (CNS) diseases. Beyond that, specific subtype of IL-32 was reported to involve in the neuroinflammation regulation in cerebral ischemia impairment, multiple sclerosis, Alzheimer's Disease, and so on. Thus, we speculate that IL-32 may participate in the regulation of the surgery-induced neuroinflammation during the parthenogenesis of PND. The isoforms, spatio-temporal regulation of IL-32 may determine its pro- or anti-inflammation properties in parthenogenesis of PND. Therefore, IL-32 could be a putative therapeutic target for the prevention and reversal of PND in the future.

Leukotriene B4 (LTB4) is a major type of lipid mediator that is rapidly generated from arachidonic acid through sequential action of 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTA4 hydrolase (LTA4H) in response to various stimuli. LTB4 is well known to be a chemoattractant for leukocytes, particularly neutrophils, via interaction with its high-affinity receptor BLT1. Extensive attention has been paid to the role of the LTB4-BLT1 axis in acute and chronic inflammatory diseases, such as infectious diseases, allergy, autoimmune diseases, and metabolic disease via mediating recruitment and/or activation of different types of inflammatory cells depending on different stages or the nature of inflammatory response. Recent studies also demonstrated that LTB4 acts on non-immune cells via BLT1 to initiate and/or amplify pathological inflammation in various tissues. In addition, emerging evidence reveals a complex role of the LTB4-BLT1 axis in cancer, either tumor-inhibitory or tumor-promoting, depending on the different target cells. In this review, we summarize both established understanding and the most recent progress in our knowledge about the LTB4-BLT1 axis in host defense, inflammatory diseases and cancer.