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Background: Hepatocellular carcinoma (HCC) seriously affects human health, especially, it easily develops multi-drug resistance (MDR) which results in treatment failure. There is an urgent need to develop highly effective and low-toxicity therapeutic agents to treat HCC and to overcome its MDR. Targeted drug delivery systems (DDS) for cancer therapy, including nanoparticles, lipids, micelles and liposomes, have been studied for decades. Recently, more attention has been paid to multifunctional DDS containing various ligands such as polymer moieties, targeting moieties, and acid-labile linkages. The polymer moieties such as poly(ethylene glycol) (PEG), chitosan (CTS), hyaluronic acid, pullulan, poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) protect DDS from degradation. Asialoglycoprotein receptor (ASGPR) and glycyrrhetinic acid receptor (GAR) are most often used as the targeting moieties, which are overexpressed on hepatocytes. Acid-labile linkage, catering for the pH difference between tumor cells and normal tissue, has been utilized to release drugs at tumor tissue. Objectives: This review provides a summary of the recent progress in ASGPR and GAR-mediated and/or pH-responsive HCC-targeted drug delivery. Conclusion: The multifunctional DDS may prolong systemic circulation, continuously release drugs, increase the accumulation of drugs at the targeted site, enhance the anticancer effect, and reduce side effects both in vitro and in vivo. But it is rarely used to investigate MDR of HCC; therefore, it needs to be further studied before going into clinical trials.

AIM: To confirm whether exosome-mediated delivery of aptamer S58 (Exo-S58) has a better antifibrotic effect than naked S58 in human conjunctival fibroblasts (HConFs) and a rat glaucoma filtration surgery (GFS) model. METHODS: To enhance the effective reaction time of aptamer S58 in vivo, we loaded aptamer S58 into exosomes derived from HEK293T cells by PEI transfection to determine the effect of Exo-S58 in HConFs and a rat GFS model. RESULTS: Exo-S58 can significantly reduce cell proliferation, migration and fibrosis in TGF-β2-induced HConFs. In an in vivo experiment, Exo-S58 treatment prolonged filtering bleb retention and reduced fibrosis compared with naked S58 treatment in GFS rats. CONCLUSION: The exosomes are safe and valid carriers to deliver aptamers. Furthermore, Exo-S58 exhibited superior antifibrotic effect than naked S58 both in HConFs cells and rat GFS models.

Persons with mental disorders (PwMDs) are a priority group for COVID-19 vaccination, but empirical data on PwMDs' vaccine uptake and attitudes toward COVID-19 vaccines are lacking. This study examined the uptake, acceptance, and hesitancy associated with COVID-19 vaccines among Chinese PwMDs during China's nationwide vaccine rollout. In total, 906 adult PwMDs were consecutively recruited from a large psychiatric hospital in Wuhan, China, and administered a self-report questionnaire, which comprised standardized questions regarding sociodemographics, COVID-19 vaccination status, attitudes toward COVID-19 vaccines, and psychopathology. Vaccine-recipients were additionally asked to report adverse events that occurred following vaccination. PwMDs had a much lower rate of vaccination than Wuhan residents (10.8 vs. 40.0%). The rates of vaccine acceptance and hesitancy were 58.1 and 31.1%, respectively. Factors associated with vaccine uptake included having other mental disorders [odds ratio (OR) = 3.63], believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 3.27), being not worried about the side effects (OR = 2.59), and being an outpatient (OR = 2.24). Factors associated with vaccine acceptance included perceiving a good preventive effect of vaccines (OR = 12.92), believing that vaccines are safe (OR = 4.08), believing that ≥50% of vaccine-recipients would be immune to COVID-19 (OR = 2.20), and good insight into the mental illness (OR = 1.71). Adverse events occurred in 21.4% of vaccine-recipients and exacerbated pre-existing psychiatric symptoms in 2.0% of vaccine-recipients. Nevertheless, 95.2% of vaccine-recipients rated adverse events as acceptable. Compared to the 58.1% vaccine acceptance rate and the 40.0% vaccination rate in the general population, the 10.8% vaccine coverage rate suggested a large unmet need for COVID-19 vaccination in Chinese PwMDs. Strategies to increase vaccination coverage among PwMDs may include provision of reliable sources of information on vaccines, health education to foster positive attitudes toward vaccines, a practical guideline to facilitate clinical decision-making for vaccination, and the involvement of psychiatrists in vaccine consultation and post-vaccination follow-up services.

Purpose: To evaluate the optical quality and tear-film dynamics in patients with aqueous-deficient or evaporative subtype of dry eye disease (DED). Methods: Twenty-five aqueous-deficient dry eye (ADDE) patients, 25 DED patients with meibomian gland dysfunction (MGD), and 25 healthy subjects were included in this study. Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Dynamic recording with a double-pass system (Optical Quality Analysis System [OQAS]) was performed in right eyes. Scattered light was measured as the objective scatter index (OSI) at 0.5-second intervals over 20 seconds without blinking. Then, we recorded OSI every 0.5 seconds within a 20-second period with the subjects asked to blink freely. Several parameters were established to evaluate the dynamic alterations of optical quality and the effects of blinks: OSI, OSI standard deviation (SD), ΔOSI, ΔOSI/time, blinking change (BC), and blinking frequency (BF). Additional clinical examination included tear film break-up time (BUT), Schirmer I test (SIT), fluorescein staining grade (FL), meibomian gland quality, meibomian gland expressibility, and meibomian gland drop-out. Results: The OSI, SD, ΔOSI, ΔOSI/time, BC, and BF were significantly higher in DED patients than controls (P < 0.01, respectively). The OSI, SD, ΔOSI, ΔOSI/time, BC, and BF were significantly higher in patients with MGD than patients with ADDE (P < 0.01). In the MGD group, BUT, FL staining score, lid abnormality, meibomian gland expressibility, and meibomian gland drop-out were correlated with Δ OSI and Δ OSI/time. Conclusion: Dry eye patients with MGD had significant alterations of optical quality compared with ADDE patients. The double-pass system has potential to be a useful quantitative method to evaluate the optical quality and tear-film dynamics in patients with dry eye.

Herein, a dual-response fluorescent sensor, L, based on pyrazolopyrimidine was designed and developed for the simultaneous detection of Ni2+ and Cu2+ ions in the presence of other metal ions; the structural characterization of L was carried out by FTIR spectroscopy, NMR spectroscopy, HRMS and X-ray diffraction analysis. The sensor L effectively displayed fluorescence quenching towards the Ni2+ and Cu2+ ions with high sensitivity without interference from other metal ions. The results reveal that L binds to Ni2+ and Cu2+ in a 2 : 1 pattern, which matches well with the result of the Job's plot. The association constants of L with Ni2+ and Cu2+ were 3.2 × 104 M−1 and 7.57 × 104 M−1, respectively. The detection limits (DLs) are down to 8.9 nM for Ni2+ and 8.7 nM for Cu2+. The fluorescence imaging of L in T-24 cells was investigated because of the low cytotoxicity of L, indicating that L could be used to detect Ni2+ and Cu2+ in living cells.

To study the antitumor activity and action mechanism of Ru(II) polypyridyl plumbagin (PLN) complexes, four complexes [Ru(PLN)(DMSO)

The rare earth metal Gd(III), Yb(III), Lu(III), Eu(III), Tb(III) and Ho(III) complexes 1-6 with 2-((2-(pyridin-2-yl)hydrazono)methyl)quinolin-8-ol (H-L) as ligands were synthesized. The in vitro cytotoxicity assay indicated that the cytotoxicity of 1 was equivalent to cisplatin and higher than that of H-L and other complexes towards T24 tumor cells. The mechanism study indicated that 1 caused significant up-regulation of the proteins p27, p21 and p53 in T24 cells and cell cycle arrest in G2 phase. In addition, 1 induced effective T24 cells apoptosis via mitochondrial dysfunction pathway, which was indicated by changes in mitochondrial membrane potential (Δψ), reactive oxygen species (ROS), intracellular Ca2+ and the mitochondria-related proteins (including cytochrome C (Cyt C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated x (Bax) and apoptotic protease activating factor-1 (Apaf-1)). Moreover, 1 could activate caspase-3/8/9 in T24 cells. Therefore, complex 1 is a promising and potent anticancer drug candidate.

Objective To explore the potential mechanism which miR-527 targeting the heparan sulfate 6-O-endosulfatase (SULF2) regulates TGF-β/SMAD signaling pathway induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC). Methods 38 pairs of lung tumor biopsies and corresponding paracancerous biopsies were obtained from NSCLC patients with surgical resection, normal human bronchial epithelial BEAS-2B cells and five NSCLS cell lines were applied for our study. miR-527 and SULF2 expression were determined by qRT-PCR and immunohistochemistry. MiR-527 and SULF2 biological link were predicted by Targetscan.org and tested by dual luciferase. Cells proliferation and apoptosis were respectively detected by EDU staining and flow cytometry. Cells migration was examined by transwell and scratch-wound assay. Expression of proteins related to EMT and TGF-β/SMAD signaling pathway, such as E-cadherin, N-cadherin, p-Samd3 and p-Smad2, was detected by western blot. ResultsmiR-527 expression was decreased in lung tumor tissues and NSCLS cell lines, conversely, SULF2 expression was significantly increased. In addition, we found that miR-527 targeted 3'-untranslated regions (3'-UTR) of SULF2 and mediated its expression. Overexpression of miR-527 evidently suppressed NSCLC proliferation, invasion and EMT via TGF-β/SMAD signaling pathway. Moreover, the silence of SULF2 exhibited a similar effect. Conclusion miR-527 targeting SULF2 down-regulated SULF2 expression, concurrently, suppressed NSCLC epithelial-mesenchymal transition and invasion via inhibiting TGF-β/SMAD signaling pathway.

AimsSuicide attempt is an important indicator of suicide and potential future mortality. However, the prevalence of suicide attempts has been inconsistent across studies. This meta-analysis aimed to examine the prevalence of suicide attempts in individuals with schizophrenia and associated correlates.MethodsRelevant publications in Embase, PsycINFO, PubMed, Web of science and Cochrane were systematically searched. Data on the prevalence of suicide attempts in individuals with schizophrenia were pooled using a random-effects model.ResultsThirty-five studies with 16 747 individuals with schizophrenia were included. The pooled lifetime prevalence of suicide attempts was 26.8% (95% CI 22.1–31.9%;I2= 97.0%), while the 1-year prevalence, 1-month prevalence and the prevalence of suicide attempts from illness onset were 3.0% (95% CI 2.3–3.7%;I2= 95.6%), 2.7% (95% CI 2.1–3.4%;I2= 78.5%) and 45.9% (95% CI 42.1–49.9%;I2= 0), respectively. Earlier age of onset (Q= 4.38,p= 0.04), high-income countries (Q= 53.29,p< 0.001), North America and Europe and Central Asia (Q= 32.83,p< 0.001) were significantly associated with a higher prevalence of suicide attempts.ConclusionsSuicide attempts are common in individuals with schizophrenia, especially those with an early age of onset and living in high-income countries and regions. Regular screening and effective preventive measures should be implemented as part of the clinical care.

Wideband electromagnetic scattering from multiple objects partially buried beneath rough earth soil surfaces is an important topic during recent years due to its extensive applications in several fields, such as ground remote sensing, ground penetrating radar applications, and target identification. Due to the advantages of finite-difference time-domain (FDTD) method in calculating the wideband electromagnetic scattering from rough surface in the presence of multiple objects, the FDTD method under ultrawideband (UWB) Gaussian pulse wave incidence is utilized in the present study for analyzing the frequency response of rough soil surfaces with periodically distributed multiple rectangular cross-section columns buried partially. In this paper, the dielectric property of the actual land surface is expressed using the four-component model, and the actual rough land surface is simulated utilizing Monte Carlo method with exponential correlation function. The emphasis of the present study is on analyzing the wideband response signatures of composite backscattering coefficient varying with frequency on the basis of extensive numerical simulations, in particular for calculating and discussing in detail the influence of the root-mean-square height and the correlation length of rough soil surface, soil moisture, the length and the width of the rectangular cross-section column, separation distance, burial depth, and tilt angle on the composite backscattering coefficient.

Eukaryotic initiation factor 5A2 (eIF5A2), as one of the two isoforms in the family, is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer. Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers. Accumulated evidence shows that eIF5A2 initiates tumor formation, enhances cancer cell growth, increases cancer cell metastasis, and promotes treatment resistance through multiple means, including inducing epithelial-mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Expression of eIF5A2 in cancer correlates with poor survival, advanced disease stage, as well as metastasis, suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target. This review focuses on the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in cancer, especially in human digestive system neoplasms.

Objective As a non-competitive N-methyl- d -aspartate receptor antagonist, memantine has been used to treat major mental disorders including schizophrenia, bipolar disorder, and major depressive disorder (MDD). This meta-analysis systematically investigated the effectiveness and tolerability of adjunctive memantine for patients with schizophrenia, bipolar disorder, and MDD. Methods Only randomized controlled trials (RCTs) were identified and included in the study. Data of the three disorders were separately synthesized using the RevMan 5.3 software. Results Fifteen RCTs (n = 988) examining memantine (5–20 mg/day) as an adjunct treatment for schizophrenia (9 trials with 512 patients), bipolar disorder (3 trials with 319 patients), and MDD (3 trials with 157 patients) were analyzed. Memantine outperformed the comparator regarding total psychopathology with a standardized mean difference (SMD) of −0.56 [95% confidence interval (CI): −1.01, −0.11; I2 = 76%, P = 0.01] and negative symptoms with an SMD of −0.71 (95% CI: −1.09, −0.33; I2 = 74%, P = 0.0003) in schizophrenia, but no significant effects were found with regard to positive symptoms and general psychopathology in schizophrenia, or depressive and manic symptoms in bipolar disorder or depressive symptoms in MDD. Memantine outperformed the comparator in improving cognitive performance in schizophrenia with an SMD of 1.07 (95% CI: 0.53, 1.61; P Conclusions Memantine as an adjunct treatment appears to have significant efficacy in improving negative symptoms in schizophrenia. The efficacy and safety of adjunctive memantine for bipolar disorder or MDD needs to be further examined. Review registration PROSPERO: 42018099045.

Objective Findings on the efficacy of intranasal oxytocin (IN-OT) in schizophrenia have been inconsistent. This meta-analysis of double-blind randomized controlled trials (RCTs) examined the efficacy and tolerability of adjunctive IN-OT in the treatment of schizophrenia. Methods Standardized mean differences or risk ratios (SMDs or RRs) with their 95% confidence intervals (CIs) were used to synthesize the results of studies included in the meta-analysis. Results Ten RCTs (n = 344) with 172 schizophrenia subjects on adjunctive IN-OT [range = 40–80 International Units (IU)/day] and 172 schizophrenia subjects on adjunctive placebo over 2–16 weeks were included. No significant differences regarding total psychopathology measured with the total Positive and Negative Syndrome Scale (PANSS) or the Brief Psychiatric Rating Scale (BPRS) [8 RCTs, n = 203; SMD: −0.08 (95%CI: −0.53, 0.37), P = 0.74, I 2 = 59%] and the positive, negative and general symptom scores [SMD: −0.20 to −0.04 (95%CI: −0.75, 0.36), P = 0.28 to 0.78; I 2 = 0% to 72%] were found between the IN-OT and placebo groups. Similarly, subgroup analyses for total psychopathology found no group differences. Dose-response effect analyses showed that only 80 IU/day IN-OT had superiority over placebo in improving total psychopathology (P = 0.02) and positive symptom score (P = 0.01). No group differences between adjunctive IN-OT and placebo regarding discontinuation due to any reason [RR: 1.12 (95%CI: 0.67, 1.88), P = 0.67, I 2 = 0%] and adverse drug reactions were found. Conclusions Although the meta-analysis did not show a positive effect in general, the higher dose of adjunctive IN-OT (80 IU/day) appears to be efficacious and safe in improving total psychopathology and positive symptoms in schizophrenia. Review registration CRD42017080856

In order to fast and accurately calculate the composite scattering from time-varying sea surfaces with a Low-flying small target above it, a hybrid algorithm of Kirchhoff approximation (KA) and method method-of-moments (MoM) is utilized in this paper for analyzing the Doppler spectrum signatures of Low-flying small target located above rough sea surfaces. The effect of sea state parameters, incidence angles, the speed of flying target, the distance between the target and the sea surfaces, the shape of the target’ cross-section on Doppler spectrum signatures of a low-flying small target above time-varying sea surface is investigated in detail in this paper.

IL-6 and IL-23 are both pleiotropic cytokines involved in the regulation of the immune response, inflammation, and hematopoeisis. They also could mediate effector cells and tolerance mediated by cells with regulatory function. Inflammatory bowel disease (IBD) is associated with a reduced ratio of Treg cells ato Th17 effector cells in peripheral blood and is characterised by a pro-inflammatory cytokine microenvironment which supports the continued generation of Th17 cells. It is well described in adults but little is known in a pediatric population. This study was aimed to investigate the role of IL-6, IL-23 and its association with Treg and Th17 subsets in pediatric IBD patients. Peripheral blood mononuclear cells from patients and controls were stimulated with PMA, ionomycin, and brefeldin A. The frequencies of CD4+Foxp3+ cells, and CD4+IL17a+ cells were analyzed by flow cytometry. The serum level of IL-6 and IL-23 was determined by Elisa kit. The mRNA expression of Foxp3, IL-17a, IL-6 and IL-23 was detected by real-time quantitative PCR. The ratio of Treg/Th17 decreased in pediatric IBD patients, and it strongly correlated with IL-6 and IL-23. The present study provides a quantitative analysis regarding the Th17/Treg cell balance in peripheral blood of children with IBD and its association with serum IL-6 and IL-23 level.

Background Electroconvulsive therapy (ECT) has been widely used in treating older adult patients with major depressive disorder. The results of randomized controlled trials (RCT) are mixed. This study systematically examined the efficacy and safety of ECT versus antidepressants (AD) in older adult patients with major depressive disorder. Methods A literature search was conducted independently by two reviewers using the PubMed, Embase, PsycINFO, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases from their inceptions until 17 May 2017. The Cochrane risk of bias and Jadad scale were used to assess the quality of RCT included in the systematic review. Results Five RCT (n = 374; mean age: 66.0-66.4 years; men: 36.4-58.3%) all conducted in China were identified, including three RCT (n = 203) with ECT alone and two RCT (n = 171) with ECT-AD co-treatment. In two of the three RCT, ECT alone was superior to AD monotherapy in improving depressive symptoms as assessed by the Hamilton Depression Scale and by clinical judgement at the conclusion of the course of ECT. Both RCT of AD-ECT co-treatment showed a significant reduction in the Hamilton Depression Scale total score after ECT compared with AD monotherapy. The response rate ranged from 80% to 97.5% in the ECT groups and from 63.4% to 73.3% in the AD groups. Rates of adverse reactions were similar between ECT and AD groups in studies with available data. Only one RCT reported the discontinuation rate without a significant group difference. Conclusions This systematic review showed that ECT appears to be an effective and safe treatment for older adult patients with major depressive disorder. Further high-quality studies with extended follow-up are warranted.

Objective Raloxifene, a selective estrogen receptor modulator, has been used in treating postmenopausal women with schizophrenia with inconsistent results. This meta-analysis of randomized, double-blind, placebo-controlled trials (RCTs) examined its efficacy and safety for postmenopausal women with schizophrenia. Method Standardized mean differences (SMDs) and risk ratio (RR) together with their 95% confidence intervals (CIs) were calculated using the random effects model. Results The meta-analysis included 5 RCTs (n = 240) comparing raloxifene (n = 125, 60 or 120 mg/day) with placebo (n = 115). Adjunctive raloxifene outperformed placebo with regard to the Positive and Negative Syndrome Scale (PANSS) total psychopathology [n = 240, SMD:-0.64 (95%CI:-0.90, −0.37), P Conclusion Adjunctive raloxifene appears to be effective and safe in improving psychotic symptoms for postmenopausal women with schizophrenia. Review registration: CRD 42017059946

Interest in the stimuli-responsive polymers has been going on for decades, and a lot of work has been dedicated to the development of environmentally sensitive macromolecules that can be crafted into novel responsive carrier materials. This article reviews the state-of-the art in smart responsive carriers for controlled drug delivery applications. And the preparation methods of different responsive materials, sustained and controlled release performance are summarized. The significance and future of smart responsive materials are also commented.

1D band-limited weierstrass fractal rough surface is used to simulate the natural rough land surface, the composite electromagnetic scattering from 1D band-limited weierstrass fractal land surface with buried target is studied using FDTD, the angle distribution curves of the composite bistatic scattering coefficient is obtained by numerical calculation, the variation of the composite bistatic scattering coefficient with fractal Dimension, the root-mean-square of height fluctuation, the target size, the slope angle of target, the buried depth of target is calculated, which is analyzed and discussed in detail at the same time, the characteristics of the composite electromagnetic scattering from fractal land surface with buried plate shape target is obtained

In the present study, organic-inorganic hybrid mesoporous material (HMC) were used to optimize the removal rate for Cr (VI) by applying Response Surface Methodological approach. Batch mode experiments were also carried out to assess the adsorption equilibrium in aqueous solution. The effect of three parameters, that is pH of the solution (1.52.5), initial concentration (100500 mg/L) and adsorbent dose (0.050.15 g/ 50 mL) was studied for the removal of Cr (VI) by HMC. BoxBehnken model was used as an experimental design. The optimum pH, adsorbent dose and initial Cr (VI) concentration were found to be 2.0, 0.05 g/L and 500 mg/L, respectively. Under these conditions removal adsorption capacity of Cr (VI) was found to be 337..

Hetaoyuan formation of Palaeogene in Biyang sag experienced the process of sedimentation during the main depressing period. Lithological traps were formed by the Sandstone-conglomerate bodies as favorite targets for oil and gas exploration in the southeast of Biyang sag. In this study, seismic profile, cores and well loggings as main data are used to analyze the micro-facies of subaqueous fan complex system. Methods such as Phasing concertion, spectrum decomposition, and strata slice play important roles in the study of facies evolution and distribution in high-resolution sequence framework of the upper member of the third Hetaoyuan formation. Subsequently, All of the coarse-grained turbid sandstone and the distributary channels sediments are potential reservoirs for oil and gas storage.

Purpose Physical restraint (PR) is a highly controversal topic in psychiatry. Little is known about PR among psychiatric inpatients in China. This study examined the frequency of PR and its relationships with demographic and clinical characteristics among a large psychiatric institution in the Hunan Province, China. Design and Methods The study included a consecutively assessed sample of 160 psychiatric inpatients. Sociodemographic and clinical data including use of PR were collected from the medical records using a form designed for this study and confirmed via interview. Findings The frequency of PR was 51.3% in the whole sample; 63.2% among female and 39.2% among male patients. In multiple logistic regression analysis PR was independently associated with male gender (p = 0.001, odds ratio [OR] = 0.2, 95% confidence interval [CI] 0.1–0.6), less outpatient treatment prior to admission (p = 0.03, OR = 0.3, 95% CI 0.1–0.9), more frequent use of mood stabilizers (p = 0.002, OR = 5.6, 95% CI 1.9–16.7), more aggressive behavior prior to admission (p = 0.002, OR = 1.1, 95% CI 1.04–1.2), and younger age (p = 0.04, OR = 0.97, 95% CI 0.93–0.99). Practice Implications PR is very common in clinical practice in China. Its demographic and clinical correlates are similar to findings in Western settings.