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Purpose: As a new category proposed in the International Classification of Diseases (11th Revision) (ICD-11), the reliability and clinical utility of ICD diagnostic guidelines for gaming disorder (GD) in the Chinese population have not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and cultural applicability of ICD diagnostic guidelines for GD in China and its comparability with Internet GD (IGD) in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5). Methods: Participants included 21 paired clinical raters consisting of seven psychiatrists and 200 gaming players aged from 15 to 18 years with different risk levels of Internet addiction based on the scores of Young's Internet Addiction Test. Each participant received a semi-structured face-to-face interview by paired clinical raters at the same time. Then clinical raters made the diagnosis and filled the clinical utility questionnaire independently according to the diagnostic guidelines for GD in both ICD-11 and DSM-5. Results: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0.545 (0.490-0.600, p < 0.001) and 0.622 (0.553-0.691, p < 0.001) for ICD-11 and DSM-5 diagnostic guidelines, respectively, for GD. The diagnostic consistency was 0.847 (0.814-0.880, p < 0.001) between GD in ICD-11 and IGD in DSM-5. Meanwhile, 86.7% of responses that agreed with the ICD-11 diagnostic guidelines for GD provided enough detailed implementation characteristics and showed good overall clinical applicability (86.0%), specificity (94.4%), usefulness (84.1%), and acceptable cultural adaptation (74.8%). GD in ICD-11 was slightly more accepted than IGD in DSM-5 ( p < 0.001), while the clinical efficiency of ICD-11 was inferior to that of DSM-5 ( p < 0.001). Conclusion: This study indicates that the ICD-11 diagnostic guidelines for GD have acceptable clinical reliability and high consistency with IGD in DSM-5. Their clinical applicability and cultural adaption are comparable with those of DSM-5. Although the guidelines still need to be adjusted for better implementation in China, this is already a great step committed to reducing the serious consequences caused by excessive gaming behaviors through effective identification and normative diagnosis, especially for adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ma, Wang, Li, Lu, Long, Li, Wu, Jiang, Du, Li, Wang, Ma, Li, Hui, Zhao, Zhong and Zhao.)

Second near-infrared (NIR-II) absorbing organic photothermal agents (PTAs) usually suffer from laborious and time-consuming synthesis; therefore, it is of importance to develop a simple and easy-to-handle method for the preparation of NIR-II PTAs. Charge-transfer complexes (CTCs) can be easily used to construct NIR-II absorbing PTAs, although the relationship between their molecular structure and photophysical properties is yet to be uncovered. Herein, three kinds of electron donors with different substitutions (chloroethyl, ethyl, and methyl) were synthesized and assembled with electron-deficient F4TCNQ to afford corresponding CTC nanoparticles (Cl-F4, Et-F4, and Me-F4 NPs). The large energy gap (>0.61 eV) between HOMO of the donor and LUMO of the acceptor made the CTCs exhibit high charge transfer (>0.93) and dramatic differences in photophysical properties. Additionally, Et-F4 NPs possess the highest NIR-II absorption ability and best photothermal effect because of different packing modes (mass extinction coefficient of 11.0 L g -1 cm -1 and photothermal conversion efficiency of 40.2% at 1060 nm). The mixed stacking mode formed strong charge-transfer absorption bands, indicating that the photophysical properties of CTCs can be tailored by changing the molecular structure and aggregate behaviors. Furthermore, Et-F4 NPs with cyano groups could specifically react with cysteine to block the intracellular biosynthesis of GSH and result in ROS accumulation and ferroptosis. Et-F4 NPs possess outstanding antitumor efficacy for the combined actions of NIR-II triggered photothermal killing effect and ferroptosis in vivo .

Female moths use sex pheromones to attract males, and corresponding regulatory mechanism underlying sex pheromone biosynthesis is species-dependent. However, the detailed mechanism involved in sex pheromone biosynthesis in Ostrinia furnacalis has not yet been fully addressed. In the present study, transcriptome sequencing of O. furnacalis pheromone glands screened a serials of candidate genes involved in sex pheromone biosynthesis. Our analysis showed that sex pheromone release in O. furnacalis females arrives its peak at the 2 nd scotophase, consistent with its mating behavior. Pheromone biosynthesis-activating neuropeptide (PBAN) was confirmed to regulate sex pheromone biosynthesis, and Ca 2+ is the secondary messenger of PBAN signaling in O. furnacalis . The functional analysis of candidate genes demonstrated that the decreased mRNA levels or activities of calcineurin (CaN) and acetyl-CoA carboxylase (ACC) led to significant decrease in sex pheromone production and female capability to attract males, as demonstrated by RNAi-mediated knockdown and pharmacological inhibitor assay. Most importantly, the activities of CaN and ACC depend on the activation of PBAN/PBANR/Ca 2+ . Furthermore, fatty-acyl reductase 14 was involved in PBAN-mediated sex pheromone biosynthesis. Altogether, our results demonstrated that PBAN regulates sex pheromone biosynthesis through PBANR/Ca 2+ /CaN/ACC pathway to promote sex pheromone biosynthesis in O. furnacalis and provided a reference for non-model organism to study neuropeptide signal transduction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Zhou, Li, Liu, Zhao, Wei, Du and An.)

Semiconductor-based photocatalytic technology, as a green and promising avenue in response to the abuse of antibiotic pollution and human health crisis, is restricted by the limited photo-absorption and fast recombination of photogenerated carriers. In this paper, all these challenges were settled by AgBr particles incorporated into oxygen-deficient BiOBr nanosheets, forming novel oxygen vacancy (OV)-rich 2D/0D Z-scheme heterojunctions. Z-scheme photocatalytic system has an effective separation rate of photogenerated carriers and an ability to maintain original redox capacity. Moreover, introducing OVs in the Z-scheme can not only improve the visible light absorption ability, but also serve as recombination centers, thus promoting the separation of electrons and holes. Notably, the photocatalytic activity of 2D/0D BiO 1-X Br/AgBr (2:1) was significantly improved under the irradiation of visible light, removing 81% of tetracycline after 25 min, which was about 2.62 times and 2.03 times as high as those of BiO 1-X Br and AgBr, respectively. In addition, the 2D/0D BiO 1-X Br/AgBr (2:1) indicated high photocatalytic stability and reusability, and its tetracycline degradation efficiency remained stable after five cycles. In summary, this work suggests that the photocatalysts have a great potential to remove TC and provides a possible strategy for purifying water., (© 2021 IOP Publishing Ltd.)

Pyruvate kinase (PYK) is a speed-limited enzyme of glycolysis that catalyzes the formation of pyruvate, and plays an important role in acetyl-CoA synthesis. The acetyl-CoA is the precursor of sex pheromone biosynthesis in Helicoverpa armigera . However, the role of PYK in sex pheromone biosynthesis remains elusive. Here, PYK in H. armigera ( HaPYK ) was found to be highly expressed in the pheromone glands (PGs). The developmental expression profile of HaPYK was consistent with the fluctuation of sex pheromone release. Function analysis revealed that the knockdown of HaPYK led to a decrease in the levels of pyruvic acid and acetyl-CoA in PGs, which in turn caused a significant decrease in cis-11-hexadecenal (Z11-16: Ald) production, female capability to attract males, and mating frequency. Further study demonstrated that sugar feeding (5% sugar) increased the transcription and enzyme activity of HaPYK, thereby facilitating sex pheromone biosynthesis. Moreover, pheromone biosynthesis activating neuropeptide (PBAN) upregulated HaPYK activity through protein kinase C (PKC), as shown by PKC-specific inhibitor analysis. Altogether, our results revealed that PBAN activated HaPYK by Ca 2+ /PKC, thereby regulating the synthesis of pyruvate and subsequent acetyl-CoA, ensuring the supply of sex pheromone precursor, and finally facilitating sex pheromone biosynthesis and mating behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yao, Zhang, Chang, Li, Zhao and An.)

Objective: This study aimed to evaluate whether ultrasound-guided techniques are superior compared to traditional palpation techniques in patients undergoing radial artery catheterization (RAC)., Methods: Electronic databases of PubMed, Embase, and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs). The relative risks (RRs) or weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were used to calculate the pooled effect estimates using the random effects model for categories and continuous data, respectively., Results: A total of 19 RCTs comprising a total of 3220 individuals were selected for final analysis. The pooled RR suggested that ultrasound-guided techniques were associated with higher incidence of first attempt success than traditional palpation techniques (RR, 1.39; 95% CI, 1.21-1.59; P < 0.001). Moreover, we noted that ultrasound-guided techniques were associated with fewer mean attempts to success (WMD, -0.80 s; 95% CI, -1.35 to -0.25; P = 0.004) and a shorter mean time to success (WMD, -41.18 s; 95% CI, -75.43 to -6.93; P = 0.018) than traditional palpation techniques. Furthermore, individuals using ultrasound-guided techniques had a reduced risk of hematoma (RR, 0.40; 95% CI, 0.22-0.72; P = 0.003)., Conclusions: This study indicated that ultrasound-guided techniques were superior compared to traditional palpation techniques for RAC in terms of efficacy and complications., (Copyright © 2020. Published by Elsevier Inc.)

COVID-19 infection can affect the cardiovascular system. We sought to determine if left ventricular global longitudinal strain (LVGLS) is affected by COVID-19 and if this has prognostic implications. Materials & methods: Retrospective study, with LVGLS was measured in 58 COVID-19 patients. Patients discharged were compared with those who died. Results: The mean LV ejection fraction (LVEF) and LVGLS for the cohort was 52.1 and -12.9 ± 4.0%, respectively. Among 30 patients with preserved LVEF (>50%), LVGLS was -15.7 ± 2.8%, which is lower than the reference mean LVGLS for a normal, healthy population. There was no significant difference in LVGLS or LVEF when comparing patients who survived to discharge or died. Conclusion: LVGLS was reduced in COVID-19 patients, although not significantly lower in those who died compared with survivors.

The COVID-19 infection adversely affects the cardiovascular system. Transthoracic echocardiography has demonstrated diagnostic, prognostic and therapeutic utility. We report biventricular myocardial strain in COVID-19. Methods: Biventricular strain measurements were performed for 12 patients. Patients who were discharged were compared with those who needed intubation and/or died. Results: Seven patients were discharged and five died or needed intubation. Right ventricular strain parameters were decreased in patients with poor outcomes compared with those discharged. Left ventricular strain was decreased in both groups but was not statistically significant. Conclusion: Right ventricular strain was decreased in patients with poor outcomes and left ventricular strain was decreased regardless of outcome. Right ventricular strain measurements may be important for risk stratification and prognosis. Further studies are needed to confirm these findings.

The proportion of Fe2+ and Fe3+ in Fe-based nanozymes is a key point in determining their catalytic activity. However, it is hard to adjust the Fe2+/Fe3+ ratio in nanozyme systems to achieve the best catalytic performance. In this work, we successfully regulate Fe2+/Fe3+ ratios in a wide range of 0.81-1.45 based on a novel porous platform of Fe doped silica hollow spheres. The homogeneous distribution and stable fixation of Fe components in Fe doped silica hollow spheres facilitate the valence regulation of Fe in the reduction heating in H2/Ar. When the Fe doped spheres (FeOx@SHSs) were used as nanozymes, different Fe2+/Fe3+ ratios have shown to influence the peroxidase-like catalytic activity greatly. The highest activity at the ratio of 1.41 should be due to the combined effects of the accelerated reaction rate by Fe2+ and the enhanced catalytic cycle efficiency by Fe3+. The FeOx@SHSs-based nanozyme is further applied to construct a facile colorimetric biosensing system, which exhibited extremely sensitive determination of glucose. This work presents an effective platform for controlling Fe valences and optimizing the peroxidase-like activity for catalytic processes or sensing systems.

Burn injury leads to mitochondrial dysfunction and autophagy, also known as mitophagy. The alleviation of mitochondrial damage may be a potential method for the treatment of burn injury and complications. In this animal study, we analyzed the expression of mitochondrial damage- and mitophagy-related factors, specifically PINK1 and PRKN. The results showed mitochondria damage in the skin; compared with the normal control group, genes involved in the mitochondrial damage, such as Nrf-1, UQCRC2, CYC1, and NDUFA9, as well as in the mitophagy, including PINK1, PRKN, MFN1, and USP30, were differentially expressed. Furthermore, PINK1 interacted with PRKN and participated in mitophagy in the skin. In conclusion, our data reveal more about the mechanism underlying mitophagy in burns, providing a potential clinical treatment., (Copyright © 2020 Elsevier Ltd and ISBI. All rights reserved.)

The human neuropeptide Y (NPY) Y 2 receptor (Y 2 R) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y 2 R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y 2 R bound to a selective antagonist JNJ-31020028 at 2.8 Å resolution. The structure reveals molecular details of the ligand-binding mode of Y 2 R. Combined with mutagenesis studies, the Y 2 R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y 1 R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design.

This study aims to show our institute's experience in the treatment of HH and its associated facial deformities in adults and growing adolescents and to investigate condylar remodeling and volumetric changes and long-term stability of orthognathic surgery in adults. The study included consecutive patients with clinical and radiological features of HH who underwent high condylectomy with or without simultaneous orthognathic surgery from 2013 to 2018. The clinical outcomes were assessed based on functional activities, TMJ pain, and recurrence. Postoperative 3D condylar remodeling and orthognathic stability were evaluated with the use of ITK-Snap and 3D Slicer. Thirteen patients (8 females and 5 males) with a mean age of 26.3 ± 5.79 years (range; 13-34 years) were included with facial asymmetry as the chief complaint. The patients were followed up for a minimum of 12 months and a maximum of 4 years (mean; 16.85 ± 10.04). There were no postoperative complications, and all patients achieved a satisfactory functional and aesthetic outcome using a one-stage surgical procedure. There was no incidence of recurrence or further asymmetries, with long-term stability at the selected points showing a mean difference of less than ±1 mm. The affected condylar volume was significantly reduced following high condylectomy, with mean changes between T1 and T2 of -144. 80 mm 3 (p = .012). However, the contralateral condylar volume remained stable, with a mean change of 2.54 mm 3 (p = .881). One-stage high condylectomy and orthognathic surgery is a viable measure for the treatment of HH and associated deformities in adults. High condylectomy in early adolescence could result in termination of the disease, and aesthetic improvement with further constant orthodontist-surgeon follow-up is required., Competing Interests: Declaration of competing interest None., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Aim: To investigate whether vitamin C performs well as a supplemental treatment for common cold., Method: After systematically searching through the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and Wanfang databases, 10 randomized controlled trials were selected for our meta-analysis with RevMan 5.3 software. Published in China, all 10 studies evaluated the effect of combined vitamin C and antiviral therapy for the treatment of common cold., Results: The total efficacy (RR = 1.27, 95% CI (1.08, 1.48), P = 0.003), the time for symptom amelioration (MD = -15.84, 95% CI (-17.02, -14.66), P < 0.00001), and the time for healing ( I , 95% CI (-14.98, -4.22), P = 0.0005) were better with vitamin C supplementation than with antiviral therapy alone., Conclusions: Vitamin C could be used as a supplementary therapy along with antiviral regimens to relieve patients from the symptoms of common cold., Competing Interests: The authors declare no conflict of interests regarding the publication of this paper., (Copyright © 2020 Li Ran et al.)

The GH (growth hormone)/IGFs (insulin-like growth factors) system has an important function in the regulation of growth. In this system, IGFBPs play a crucial regulatory role in IGF functions. As a member of the IGFBP family, IGFBP2 can bind to IGF and regulate IGF functions to regulate development and growth. In addition, IGFBP2 shows key regulatory functions in cell proliferation and metabolism. In this study, the igfbp2 gene was cloned from grass carp (Ctenopharyngodon idellus) liver. The ORF of grass carp igfbp2 is 834 bp long and encodes 277 amino acids. The tissue distribution results showed that igfbp2 is expressed in multiple tissues in grass carp and has a high expression level in the liver. In the OGTT, igfbp2 expression was significantly decreased in the liver and brain after 6 h of treatment with glucose. In vitro, igfbp2 expression in grass carp's primary hepatocytes was significantly suppressed by insulin after treatment for 6 and 12 h. Moreover, igfbp2 expression was markedly increased in a dose-dependent manner with glucagon incubation in grass carp's primary hepatocytes. To the best of our knowledge, this is the first report about Igfbp2 in grass carp. These results will provide a basis for the in-depth study of grass carp Igfbp2.

Glucose transporter 2 (glut2) has been studied in mammals, aves, and several fish, while the comparative studies of glut2 in common carp are still lacking. In this study, glut2 was firstly isolated and characterized from the liver of common carp. The full-length cDNA of glut2 was 2351 bp with an open reading frame (ORF) of 1512 bp, encoding 503 amino acids. Alignment of glut2 amino acid sequences from different species revealed that common carp glut2 showed higher sequence identity with teleosts, and lower homology with mammals and amphibians. Tissue distribution demonstrated that glut2 mRNA level was mainly expressed in liver, foregut, and midgut. To investigate the actions of glut2 on glucose metabolism, the level of glut2 mRNA was detected after intraperitoneal injection of glucose, human insulin and glucagon (100 ng/g), respectively. Following glucose administration, glut2 gene expression was significantly upregulated at 3 h in the foregut. However, no change was found in hepatic glut2 mRNA level, indicating that glut2 may have a role in intestinal glucose uptake rather than in the liver. Following insulin treatment, the expression of glut2 was markedly downregulated at 3 h and 6 h in the liver, and at 3 h in the foregut, respectively. Furthermore, glut2 mRNA expression was unaffected by glucagon injection in the liver and foregut. These results suggested that the expression of glut2 regulated by pancreatic hormones was different. Taken together, our studies firstly revealed the structure of the glut2 gene and its potential functions in glucose metabolism of common carp.

Background: The relationship between cancer with body mass index has been extensively reported. However, association between urinary cancers with these risk factors remains unclear, with existing reports showing conflicting findings. The current review, therefore, sought to clarify the latter association by assessing the methodological and reporting quality of existing systematic reviews on the subject., Methods: We will screen PubMed, EMBASE, and Cochrane Library databases for relevant literature and subjected the resulting articles to meta-analysis. We will adopt the AMSTAR and PRISMA checklists for assessing methodological, and reporting quality, respectively. The association between BMI and different urinary cancers will be estimated by computing the pooled relative risk (RR) and its 95% confidence interval (CI), which will be calculated from the adjusted RR, odds ratio, or hazard ratio, and 95% CI offered in the studies. Heterogeneity between studies will be assessed with the I statistic as a measure of the proportion of total variation in estimates that is due to heterogeneity, where I values of 25%, 50%, and 75% correspond to cut-off points for low, moderate, and high degrees of heterogeneity. The random effects model will be used as the pooling method when significant heterogeneity existed and the fixed effect model will be used when no heterogeneity was observed. Possible publication bias will be tested by Begg and Egger test., Conclusion: Our evidence synthesis will provide a new commentary on the current systematic review evidence for the association between BMI and the risk of different urinary cancers., Prospero Registration Number: CRD42019119459.

Imidazolium-based poly(ionic liquid)s were synthesized and used as sensing film for the adsorption of volatile organic compounds. Based on a quartz crystal microbalance system, the sensing properties of the imidazolium-based poly(ionic liquid)s on volatile organic compounds was assessed according to the position of imidazolium cation in the polymer chain (the main-chain or side-chain type) and the varied counterions. The results indicated that the imidazolium-based poly(ionic liquid)s films have much higher adsorption capability on volatile organic acids than other volatile organic compounds, which is due to the strong affinity between imidazolium group and the carboxyl group. The position of imidazolium cation in the polymer chain and counterions of the imidazolium-based poly(ionic liquid)s was found to be able to influence the selectivity and sensitivity of volatile organic acids. The main-chain imidazolium-based poly(ionic liquid)s were shown strengthen the adsorption of propionic acid vapor, while the counter ion of dicyanamide showed the highest selectivity on volatile organic acids. Based on the quartz crystal microbalance sensing system, the imidazoliumbased poly(ionic liquid)s film was shown capable of detecting volatile organic acids with a theoretical detection limit of about 3.1 ppb and a quick recovery time less than 40 seconds. The sensing performance is also stable for repeated usage and after long-time storage.

Background: Hypertension is regarded as a major and independent risk factor of cardiovascular diseases, and numerous studies observed an inverse correlation between vitamin C intake and blood pressure., Aim: Our aim is to investigate the relationship between serum vitamin C and blood pressure, including the concentration differences and the correlation strength., Method: Two independent researchers searched and screened articles from the National Library of Medicine, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP databases, and WANFANG databases. A total of 18 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 14 English articles and 4 Chinese articles., Results: In the evaluation of serum vitamin C levels, the concentration in hypertensive subjects is 15.13  μ mol/L lower than the normotensive ones (mean difference = -15.13, 95% CI [-24.19, -6.06], and P = 0.001). Serum vitamin C has a significant inverse relation with both systolic blood pressure (Fisher's  Z = -0.17, 95% CI [-0.20, -0.15], P < 0.00001) and diastolic blood pressure (Fisher's  Z = -0.15, 95% CI [-0.20, -0.10], P < 0.00001)., Conclusions: People with hypertension have a relatively low serum vitamin C, and vitamin C is inversely associated with both systolic blood pressure and diastolic blood pressure., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this paper., (Copyright © 2020 Li Ran et al.)

We report the production of fullerene microtubes (FMTs), having solid cores bisecting their tubular cavities, from solutions of mixtures of fullerene C 60 and C 70 and have demonstrated the structural transformation of FMTs to fullerene microhorns (FMHs) upon their exposure to alcohol/mesitylene mixtures at 25 °C. The conically shaped microhorns have hollow interiors and exhibit preferential recognition of silica particles over fullerene C 70 , polystyrene (PS) latex, PS hydroxylate, or PS carboxylate particles of similar dimensions due to strong electrostatic interactions between negatively charged FMHs and positively charged silica particles.

Background: Vitamin D is a fat-soluble vitamin that is related to the health of the human body and is an indispensable nutrient for human beings. Some studies indicated that type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) may be associated with vitamin D deficiency, but the current understanding of this point of view remains controversial. This study aimed to evaluate the correlation between serum 25-hydroxyl vitamin D (25 [OH] D) concentration and DPN in patients with T2DM by a meta-analysis, and to provide a reference for doctors., Methods: Relevant studies were selected from the PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP databases, and Wanfang Data Knowledge Service Platform databases dating from 2000 to December 2017. A total of 75 articles related to serum 25 (OH) D and DPN were selected from 2000 to December 2017. Based on the inclusion and exclusion criteria of the literature, a quality assessment was conducted using the Newcastle-Ottawa scale, and a meta-analysis was performed by RevMan5.3 statistical software., Results: Thirteen studies that involved a total of 2814 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis results, heterogeneity test showed that, P < .000 01, I = 92%, calculation by random effect model revealed that, the serum concentration of 25 (OH) D in T2DM combined with DPN group was lower than that in the group without DPN (weighted mean difference = -0.74, 95% confidence interval: -1.03 to -0.46) CONCLUSIONS:: Vitamin D is associated with type 2 DPN (DPN), and vitamin D deficiency can lead to an increased risk of type 2 DPN. However, more high-quality research is needed.

This study aims to explore the potential benefits of antidepressant drugs related to metabolic enzyme and drug-targeted genes, identify the optimal treatment of major depression, and provide a reference for individualized medication selection. A prospective randomized single-blind investigation was conducted for 8 weeks. A pharmacogenomic-based interpretive report was provided to the treating physician in the guided group. Patients in this group were informed that their medication selection was directed by DNA testing. In the unguided group, treatment was provided based on the clinical experience of the physician without the guidance of pharmacogenomic testing. Pharmacogenomic-based interpretive report was not provided to these patients until treatment completion. The 17-item Hamilton depression scale (HAMD-17), Hamilton anxiety scale, and treatment emergent symptom scale were used to assess the clinical efficacy and side effects at baseline and after 2, 4, and 8 weeks of treatment. Among the 80 initially enrolled patients with depression, 71 participated in the full data analysis sets and were designated into guided (31) and unguided (40) groups, respectively. No significant difference ( P > 0.05) in HAMD-17 total scores, response and remission rates was found between the guided and unguided groups at the end of the treatment. The incidence rate of adverse reaction was 55.56% in guided group and 57.89% in the unguided group. Our study suggested that pharmacogenomic testing might not considerably improve the clinical efficiency and safety for the guided group., (Copyright © 2019 Shan, Zhao, Qiu, Wu, Chen, Fang, Guo and Li.)

Objective: To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms., Methods: Data from 22 patients with complex aneurysms, diagnosed at an interventional center for blood flow diverter implantation between February 2015 and February 2016, treated in the Henan Provincial People's Hospital (Zhengzhou, China), were retrospectively analyzed. Nursing methods, including preoperative, intraoperative, and postoperative care, were analyzed., Results: All 22 patients underwent successful surgery, with no related complications or hospital mortality, and were cured in hospital., Conclusion: Interventional flow diverter therapy for patients with complex intracranial aneurysms is a new technology, and involves intensive care by nursing staff and appears to be a promising new treatment method., (© 2019 Shanghai Journal of Interventional Medicine Press. Production and hosting by Elsevier B.V. on behalf of KeAi.)

A 38-year-old man with a history of resistant hypertension for more than 10 years underwent laparoscopic-based perivascular unilateral renal sympathetic nerve denervation in 2012. After the operation, the patient's blood pressure has been controllable while the antihypertensive drug intake has decreased over 6 years. Laparoscopic-based perivascular unilateral renal sympathetic nerve denervation may be a potentially feasible and effective option in treating patients with resistant hypertension.

Cysteine-rich intestinal protein 1 (CRIP1) is overexpressed in colorectal cancer (CRC) tissues and functions as an oncogene in regulating the migration and invasion of CRC cells. However, the underlying mechanism is unclear. CRIP1 has a role in zinc absorption and functions as an intracellular zinc transport protein. Here, we aimed to focus on the function of zinc and its underlying mechanism in CRC and determine whether CRIP1 promotes invasion and CRC metastasis through excessive zinc-induced epithelial-mesenchymal transition (EMT) by affecting the phosphorylated glycogen synthase kinase (GSK)-3beta. The results showed that ZnSO 4 (Zn 2+ ) supplementation in medium increased the labile intracellular zinc content. Furthermore, excessive Zn 2+ supplementation activated the GSK3/mTOR signaling pathway in both SW620 and LoVo cells, and excessive Zn 2+ supplementation promoted migration, invasion, and EMT of SW620 and LoVo cells. This migration promotion was alleviated by the specific mTOR inhibitor rapamycin, indicating that the GSK3/mTOR signaling pathway was involved in this process. CRIP1 silencing increased the labile intracellular zinc content and inhibited EMT and GSK3/mTOR signaling pathway. CRIP1 silencing alleviated the zinc supplementation effects on migration, invasion, EMT, and GSK3/mTOR signaling pathway. In conclusion, excessive Zn 2+ promotes migration and invasion capabilities of SW620 and LoVo cells through GSK3/mTOR signaling pathway-induced EMT., Competing Interests: None.

With the many-body expansion method, an accurate global potential energy surface (PES) is constructed for SiH 2 + (X 2 A 1 ) by mapping 4762 ab initio energy points calculated on the multireference configuration interaction level including Davidson corrections with aug-cc-pV6Z Dunning's basis set. The dissociation energies and equilibrium geometries of SiH + (X 1 Σ + ) and H 2 (X 1 Σ g + ) agree well with the experimental results. The topographical characteristics of all stationary points for the SiH 2 + (X 2 A 1 ) PES are discussed in detail and compared with other theoretical and experimental results. In order to verify the validity and usability of the present PES, the dynamics calculations based on the Chebyshev quantum wave packet method are performed for the H(S2)+SiH + (X 1 Σ + )→Si + (P2)+H 2 (X 1 Σ g + ) reaction. The probabilities, the total integral cross sections, and the rate constants are computed, and the analogies with the corresponding ones of reaction H(S2) + CH + (X 1 Σ + )→C + (P2) + H 2 (X 1 Σ g + ) are also made. The reasonable dynamical behavior throughout the entire configuration space indicates that the PES is suitable for relevant dynamics investigations and serves as a building block for constructing the PES of larger molecular systems containing Si + /H.

Objective: To comprehensively compare the effects of conventional therapy combined with intravenous vitamin C and conventional therapy on viral myocarditis in children through a meta-analysis., Methods: Relevant articles including clinical trials of normal treatment combined with intravenous vitamin C and conventional therapy for viral myocarditis in children that were published between January 2000 and February 2018 were selected from PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and WANFANG database. The quality of the included studies was assessed using the Cochrane systematic review method (version 5.1.0); data quality was evaluated by two independent researchers. The total effective rate; LDH, CK, and CK-MB levels; and other indicators were analyzed using Rev Man 5.3 software., Results: Eight studies were eligible for this meta-analysis, which included a total of 426 patients in the treatment group and 363 patients in the control group. The meta-analysis results of six studies showed that the total effective rate of intravenous vitamin C combined with conventional therapy was higher than that of conventional therapy alone [Z = 5.46, 95% confidence interval (CI): 1.21 (1.13 to 1.30), P < 0.00001]; that of five studies showed that LDH levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 3.70, 95% CI: -1.88 (-2.88 to -0.88), P = 0.0002]; that of three studies showed that CK levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 4.21, 95% CI: -0.55 (-0.81 to -0.30), P < 0.0001]; that of four studies showed that CK-MB levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 13.64, 95% CI: -1.44 (-1.65 to -1.24), P < 0.00001]; that of two studies showed that CD3 levels were higher in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 2.45, 95% CI: 0.41 (0.08-0.73), P = 0.01]; that of two studies showed no significant difference in changes in CD4 levels between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.28, 95% CI: -0.21 (-1.69 to 1.28), P = 0.78]; and that of two studies showed no significant difference in changes in CD4/CD8 between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.07, 95% CI: -0.03 (-0.73 to 0.67), P = 0.94]., Conclusion: The meta-analysis results showed that intravenous vitamin C combined with conventional therapy is better than the simple, conventional therapy for the treatment of viral myocarditis in children in terms of the total effective rate and LDH, CK, and CK-MB levels.

Objective To investigate the role of CD161 + regulatory T cells (Treg) in reducing valve injury in rheumatic heart disease rats and the underlying mechanism. Methods CD161 - and CD161 + regulatory T cells (Tregs) were separated by flow cytometry and then cultured. The concentrations of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in the supernates were detected by ELISA. Rat models of rheumatic heart disease were established by mixing A type hemolytic streptococcus suspension with Freund's complete adjuvant. They were divided into control group, CD161 - Treg group and CD161 + Treg group. One week later, heart blood and mitral valve were taken from the model rats. The proportion of follicular helper T (Tfh) cells, B cells and plasma cells was detected by flow cytometry. Histopathological changes were detected by HE staining and the number of B cells and plasma cells by immunohistochemical staining. ELISA was used to detect the level of IL-21 in serum. Results The ability of CD161 + Tregs to secrete IL-10 and TGF-β was significantly higher than that of CD161 - Tregs. Compared with the rats injected with CD161 - Tregs, CD161 + Tregs could significantly reduce the damage of valve tissue and the proportion of B cells and plasma cells in valve tissue. Moreover, CD161 + Tregs injection could reduce the proportion of Tfh cells, B cells and plasma cells in rat blood and decrease the content of IL-21 in serum. Conclusion CD161 + Tregs can reduce the valve injury of rheumatic heart disease by inhibiting the proliferation and differentiation of Tfh cells and B cells.

Chiral molecules can generally exhibit different physiological and biological activities, thus triggering wide interest in chiral discrimination. Herein, we demonstrate a sensitive homoleptic cyclometalated iridium(III) complexes nanowires (Ir(piq) 3 NWs) electrogenerated chemiluminescence (ECL) sensor for high-performance discrimination of chiral molecules based on the difference in electron-transfer ability between different radicals. The developed Ir(piq) 3 NWs/ITO sensor exhibits high ECL signal and satisfying stability without the presence of co-reactant based on hot electron-induced ECL, which would spur its further application in detecting proline enantiomers. Obvious difference on the ECL intensity towards L-Pro and D-Pro is observed under the presence of high concentration of proline enantiomers, which attributes to the different electron-transfer capability between Ir + (piq) 3 and L-pro • /D-pro • . In order to attain high-performance discrimination, we construct the Ir(piq) 3 NWs/TPrA sensor to achieve chiral discrimination for trace amounts of proline enantiomers (1.0 × 10 -9 M), which attributes to the strong molecular interactions enhanced by introduction of active radical TPrA • ., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Self-assembly allows structures to organize themselves into regular patterns by using local forces to find the lowest-energy configuration. However, assembling organic and inorganic building blocks in an ordered framework remains challenging due to  difficulties in rationally interfacing two dissimilar materials. Herein, the ensemble of polyoxometalates (POMs) and cyclodextrins (CDs) as molecular building blocks (MBBs) has yielded two unprecedented POM-CD-MOFs, namely [PW 12 O 40 ] 3- and α-CD MOF (POT-CD) as well as [P 10 Pd 15.5 O 50 ] 19- and γ-CD MOF (POP-CD), with distinct properties not shared by their isolated parent MBBs. Markedly, the POT-CD features a nontraditional enhanced Li storage behavior by virtue of a unique "amorphization and pulverization" process. This opens the door to a new generation of hybrid materials with tuned structures and customized functionalities.

Purpose: Immune suppression is common in patients with advanced breast cancer but the mechanisms underlying this phenomenon have not been sufficiently studied. In this study, we aimed to identify B7 family members that were able to predict the immune status of patients, and which may serve as potential targets for the treatment of breast cancer. We also aimed to identify microRNAs that may regulate the expression of B7 family members., Methods: The Cancer Genome Atlas data from 1,092 patients with breast cancer, including gene expression, microRNA expression and survival data, were used for statistical and survival analyses. Polymerase chain reaction and Western blot were used to measure messenger RNA and protein expression, respectively. Luciferase assay was used to investigate direct microRNA target., Results: Bioinformatic analysis predicted that microRNA (miR)-93, miR-195, miR-497, and miR-340 are potential regulators of the immune evasion of breast cancer cells, and that they exert this function by targeting CD274 , PDCD1LG2 , and NCR3LG1 . We chose CD274 for further investigations. We found that miR-195, miR-497, and CD274 expression levels were inversely correlated in MDA-MB-231 cells, and miR-195 and miR-497 expressions mimic inhibited CD274 expression in vitro . Mechanistic investigations demonstrated that miR-195 and miR-497 directly target CD274 3' untranslated region., Conclusion: Our data indicated that the level of B7 family members can predict the prognosis of breast cancer patients, and miR-195/miR-497 regulate CD274 expression in triple negative breast cancer. This regulation may further influence tumor progression and the immune tolerance mechanism in breast cancer and may be able to predict the effect of immunotherapy on patients., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests.

Aim: To investigate whether vitamin C is effective in the treatment of the common cold., Method: After systematically searching the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and WANFANG databases, 9 randomized placebo-controlled trials were included in our meta-analysis in RevMan 5.3 software, all of which were in English., Results: In the evaluation of vitamin C, administration of extra therapeutic doses at the onset of cold despite routine supplementation was found to help reduce its duration (mean difference (MD) = -0.56, 95% confidence interval (CI) [-1.03, -0.10], and P = 0.02), shorten the time of confinement indoors (MD = -0.41, 95% CI [-0.62, -0.19], and P = 0.0002), and relieve the symptoms associated with it, including chest pain (MD = -0.40, 95% CI [-0.77, -0.03], and P = 0.03), fever (MD = -0.45, 95% CI [-0.78, -0.11], and P = 0.009), and chills (MD = -0.36, 95% CI [-0.65, -0.07], and P = 0.01)., Conclusions: Extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements.

Within 11-dimensional supergravity we compute the logarithmic correction to the entropy of magnetically charged asymptotically AdS&#95;{4} black holes with arbitrary horizon topology. We find perfect agreement with the expected microscopic result arising from the dual field theory computation of the topologically twisted index. Our result relies crucially on a particular limit to the extremal black hole case and clarifies some aspects of quantum corrections in asymptotically AdS spacetimes.

An efficient titania supported Au nanocluster (NC) has been prepared for the direct synthesis of useful EtOH from CO 2 and H 2 . The unique creation of an excellent synergistic effect between Au NCs and the underlying TiO 2 support, especially the anatase crystal phase with abundant oxygen vacancies, can achieve the high performance for EtOH synthesis under moderate and practical conditions.

Objective: To evaluate the recanalization efficacy and safety of a novel stent retriever in a swine model of acute arterial occlusion., Methods: The JRecan thrombectomy device, a stent retriever with a weaving stent design, was evaluated in 18 occluded cervicocerebral vessels of swine. The flow restoration effect immediately upon deployment, the reperfusion rate after retrieval, thromboembolic events, and complications were assessed. The histologic structure of the renal arteries after retriever passage was measured to further assess the safety of JRecan., Results: Immediate flow restoration was achieved in 66.7% of occlusions (12/18). The reperfusion rate was 94.4% (two Thrombolysis in Cerebral Infarction (TICI) 2b and 15 TICI 3). Distal thromboembolic events did not occur. Microscopic examination of the arteries after retrieval showed mild degrees of endothelial loss in 96.6% (29/30), fibrin or platelet deposition in 53.3% (16/30), and disruption of the internal elastic lamina in 10% (3/30), without severe pathologic lesions., Conclusions: The JRecan is highly effective at clot removal with a favorable safety profile and merits further development as a stent retriever for the treatment of acute ischemic stroke., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Black TiO2, with enhanced solar absorption and photocatalytic activity, has gained extensive attention, inspiring us to investigate the reduction of other wide-bandgap semiconductors for improved performance. Herein, we report the preparation of gray Ta2O5 nanowires with disordered shells and abundant defects via aluminum reduction. Its water decontamination is 2.5 times faster and hydrogen production is 2.3-fold higher over pristine Ta2O5. The reduced Ta2O5 also delivers significantly enhanced photoelectrochemical performance compared with the pristine Ta2O5 nanowires, including much higher carrier concentration, easier electron-hole separation and 11 times larger photocurrent. Our results demonstrate that Ta2O5 will have great potentials in photocatalysis and solar energy utilization after proper modification.

Quick non-destructive assessment of leaf chlorophyll content (LCC) is important for studying phenotypes related to plant growth and stress resistance. This study was undertaken to investigate the quantitative relationship between LCC and different vegetation indices (VIs) on both adaxial and abaxial surfaces of white poplar (Populus alba), which has dense tubular hairs on its abaxial surface, and Chinese elm (Ulmus pumila var. pendula), which does not show obvious superficial differences except for lighter colour on the abaxial surface. Some published and newly developed VIs were tested to relate them to LCC. The results showed that most of the published VIs had strong relationships with LCC on the one-surface dataset, but did not show a clear relationship with LCC when both adaxial and abaxial surface reflectance data were included. Among the reflectance indices tested, the modified Datt index, (R719-R726)/(R719-R743), performed best and is proposed as a new index for remote estimation of chlorophyll content in plants with varying leaf surface structures. It explained 92% of LCC variation in this research, and the root mean square error of the LCC prediction was 5.23 μg/cm(2). This new index is insensitive to the effects of adaxial and abaxial leaf surface structures and is strongly related to the variation in reflectance caused by chlorophyll content., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

B-cell acute lymphoblastic leukemia is the most common type of pediatric leukemia. Despite improved remission rates, current treatment regimens for pediatric B-cell acute lymphoblastic leukemia are often associated with adverse effects and central nervous system relapse, necessitating more effective and safer agents. Bafilomycin A1 is an inhibitor of vacuolar H(+)-ATPase that is frequently used at high concentration to block late-phase autophagy. Here, we show that bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibited and killed pediatric B-cell acute lymphoblastic leukemia cells. It targeted both early and late stages of the autophagy pathway by activating mammalian target of rapamycin signaling and by disassociating the Beclin 1-Vps34 complex, as well as by inhibiting the formation of autolysosomes, all of which attenuated functional autophagy. Bafilomycin A1 also targeted mitochondria and induced caspase-independent apoptosis by inducing the translocation of apoptosis-inducing factor from mitochondria to the nucleus. Moreover, bafilomycin A1 induced the binding of Beclin 1 to Bcl-2, which further inhibited autophagy and promoted apoptotic cell death. In primary cells from pediatric patients with B-cell acute lymphoblastic leukemia and a xenograft model, bafilomycin A1 specifically targeted leukemia cells while sparing normal cells. An in vivo mouse toxicity assay confirmed that bafilomycin A1 is safe. Our data thus suggest that bafilomycin A1 is a promising candidate drug for the treatment of pediatric B-cell acute lymphoblastic leukemia., (Copyright© Ferrata Storti Foundation.)

Mixed phenotype acute leukemia (MPAL) is a rare type of acute leukemia with a poor clinical outcome which lacks specific therapy. To evaluate the therapeutic efficiency of CCLG-2008 protocol used for acute lymphoblastic leukemia (ALL) in China on MPAL children who were initially diagnosed as ALL by morphology, we reviewed patients' database diagnosed as ALL and MPAL according to WHO classification and compared their outcomes from July 2008 to June 2012. Total newly enrolled ALL in this study were 309 cases by morphology, in which ten cases were identified as MPAL mainly by immunophenotyping: B+ myeloid (3/10), T+ myeloid (2/10), B + T (4/10), trilineage (1/10). Two cases were classified as intermediate risk (IR) and 8 cases were high risk (HR) according to the CCLG-2008 criteria. Only one case of IR survived and others died due to primary resistance of chemotherapy and relapse. Compared with MPAL, ALL children in IR and HR had a longer survival (28.1 vs 9.5 months, p < 0.0001) and lower relapse (16.3 vs 85.7 %, p = 0.0002). In a summary, our result indicated that MPAL in children is a poor-risk disease which needs personalized therapy to improve outcome.

Objective: To study the expression level and CpG island methylation status of miR-34b in leukemia cell lines and to research the effect of DNA methylation on the proliferation of leukemia cells regulated by miR-34b., Method: Taqman real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was carried out to detect the relative expression of miR-34b in control group (bone marrow cells of 20 children without blood disease) and 8 leukemia cell lines (U937, HL-60, MV4-11, M2R, K562, Raji, CCRF, DAMI). Methylation-specific polymerase chain reaction (MSP) was carried out to detect the methylation differences of miR-34b in control group (Bone marrow cells of 23 children without blood disease), 8 leukemia cell lines. HL-60 and K562 were treated with methyltransferase inhibitor (5-aza-2-dC) for further detection of its methylation status and expression of miR-34b. Hsa-miR-34b mimics was transfected into K562 cell by liposome, the transfection efficiency was detected by flow cytometry. The cell proliferation of hsa-miR-34b transfected group in each stage was measured with CCK-8 assay, and then compared with non-transfected group and negative control group., Result: The relative expression level of miR-34b in the group of children without blood disease and the group of leukemia cell lines were 5.22 ± 1.15, 0.03 ± 0.03. The results showed that, the group of leukemia cell lines was significantly different from the control group (t = 4.538, P < 0.01) . Eight leukemia cell lines showed methylation, the positive rate of the methyl was 100%. There was no methylation in the 23 cases of control group. After leukemia cell lines HL-60 and K562 were treated with 5-aza-2-dC, the methylated bands became obviously weakened, and the relative expression levels of miR-34b substantially increased 49.5 times and 18.8 times respectively. After hsa-miR-34b mimics was transfected into K562 cell by liposome, its transfection efficiency detected by flow cytometry was 61% and the cell proliferation was measured with CCK-8 assay from which it was found that the cell proliferation was significantly suppressed compared with the control group at 48 h (t = 9.303, P < 0.01), 72 h (t = 65.617, P < 0.01), 96 h (t = 36.878, P < 0.01) and 120 h (t = 18.748, P < 0.01) in hsa-miR-34b transfected group, with the inhibition rate of 12.2% (48 h), 45.7% (72 h), 32.5% (96 h) and 22.9% (120 h)., Conclusion: The hypermethylation of promoter leads to decrease in the expression levels of miR-34b in leukemia cell lines, which attenuate mechanism of proliferative inhibition may be one of the reasons of occurrence or development of childhood leukemia.

Rapamycin has been shown to inhibit the growth of leukemic cells via an unknown mechanism. In our current study, we show that rapamycin activates autophagy in pediatric t(1;19) pre-B acute lymphoblastic leukemia (pre-B ALL) cells and thereby inhibits proliferation and induces growth arrest in these cells. Rapamycin was found to downregulate an extensive array of positive cell cycle regulators, reduce the total DNA and RNA levels, and specifically downregulate the gene transcription of DNA pol δ1 and RNA pol II. Furthermore, we show that both rapamycin and starvation caused a downregulation of the DNA pol δ1 and RNA pol II proteins which was reversed by the autophagy inhibitor 3-MA. Consistent with the results of our autophagic flux analysis, confocal microscopy indicated that both rapamycin and starvation cause the colocalization of DNA pol δ1 and RNA pol II with GFP-LC3 at autophagosomes. This colocalization was blocked by the autophagy inhibitor bafilomycin A1 which inhibits the fusion between autophagosomes and lysosomes. These data suggest that rapamycin inhibits the growth of pediatric t(1;19) pre-B ALL cells through both transcriptional inhibition and autophagic degradation of DNA pol δ1 and RNA pol II., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: The sexual dimorphism of hepatitis B virus (HBV) -related liver diseases is related with estrogen and its receptors. Recent reports indicate that abnormal expression of estrogen receptor alpha (ESR1) may be a hallmark for the progression of liver disease and HBV carriers presenting variant ESR1 have an extremely aggressive clinical course. Here we examine whether the ESR1 polymorphisms or its haplotypes are related to HBV-related acute liver failure (ALF) risk among chronic HBV carriers in a Chinese population., Methods: A total of 1216 unrelated Han Chinese HBV carriers were recruited in this hospital-based case-control study, including 359 HBV surface antigen (HBsAg) carriers affected with ALF and 857 asymptomatic HBsAg carriers. Two ESR1 haplotype tagging polymorphisms, c.30 T > C (rs2077647) and c.453-397 T > C (rs2234693), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay., Results: We observed a significantly increased susceptibility to HBV-ALF associated with the c.30 C allele (P = 8.65 × 10-4), c.453-397 C allele (5.37 × 10-4) and [c.30 C; c.453-397 C] haplotype (Dominant model, P =0.0004, odds ratio = 1.53, 95% CI 1.23 ~ 1.96) compared with the T alleles and [c.30 T; c.453-397 T] haplotype of c.30 T > C and c.453-397 T > C polymorphisms, respectively., Conclusions: Our study suggests that [c.30 C; c.453-397 C] haplotype may be a risk factor for genetic susceptibility to HBV-related ALF in the Chinese population. It also emphasizes the importance of ESR1 in the pathophysiology of HBV-related ALF on the population level.

Aim: Transcription factor T-bet is responsible for the differentiation of naive T lymphocytes, and its expression level is linked with different responses to some viral infections, including hepatitis B virus (HBV) infection. In this report we examine whether promoter polymorphisms of the TBX21 gene (encoding T-bet) are associated with susceptibility to HBV persistence or disease progression in chronic HBV carriers., Methods: Three previously reported promoter polymorphisms, T-1993C, T-1514C and G-1499A, were analyzed by polymerase chain reaction restriction fragment length polymorphism analysis. Two common polymorphisms, T-1993C and T-1514C, were selected for genotyping in 1074 chronic HBV carriers, 310 spontaneously recovered controls and 374 HBV naive controls. Of 1074 HBV carriers, 234 were considered to be asymptomatic carriers and 840 were found to have chronic progressive liver disease including cirrhosis and hepatocellular carcinoma. Haplotypes were constructed for each subject and associations with the susceptibility to persistent HBV infection were estimated by logistic regression., Results: The -1993C allele in the TBX21 promoter was significantly more common among chronic HBV carriers compared with recovered controls (chi(2) = 6.65, P = 0.01). In contrast, the frequency of TT haplotype at positions -1993/-1514, was significantly higher in recovered controls than chronic HBV carriers (P = 0.0027, odds ratio = 1.57; 95% confidence interval, 1.16-2.12). In HBV carriers, the TBX21 promoter polymorphisms were not linked to disease progression., Conclusion: The TBX21 promoter polymorphisms do not appear to be determinant of disease progression in Chinese HBV carriers. The T-1993C polymorphism in the TBX21 promoter influences susceptibility to persistent HBV infection.

Objective: To investigate the effective dose and the possible mechanism of the anti-fatigue effect of ginsenosides and then deduce to the recommended intake of human body., Methods: Healthy adult male SD rats intook ginsenosides solution every day through stomach at doses of 50, 150, 250 mg/kg per day, other rats were divided into untreated group and model control group, given equal amount of distilled water for 30 days. Conducted exhaustive swimming experiment for rats except untreated group on the last day of gavage after 30 minutes. Determine the time of the exhaustive swimming, organ coefficient, liver glycogen, muscle glycogen, malonaldehyde (MDA) of liver cells, superoxide dismutase (SOD) of liver cells, Na+ -K+ adenosine triphosphatase (Na+ -K+-ATPase) and Ca2+ -Mg2+ adenosine triphosphatase (Ca2+ -Mg2+-ATPase) of erythrocyte, blood lactate, fumaric reductase., Results: The body weight of rats middle, high dose group were higher than that in model control group after exhaustive swimming (P < 0.05). The time of the exhaustive swimming of high dose group were longer than model control group (P < 0.05). Some organ coefficient of model control group have statistically significant compared with other groups (such as brain, kidney, adrenal, thymus coefficient) (P < 0.05). The activity of SOD of liver cells of untreated group, middle dose group and high dose group were higher than model control group and low dose group (P < 0.05), but the level of MDA of liver cells of them were lower than model control group and low dose group (P < 0.01), the activity of Na+ -K+-ATPase of erythrocyte of untreated group and high dose group were higher than model control group (P < 0.05), but the activity of Ca2+ -Mg2+-ATPase of erythrocyte of each group had no statistical significance (P > 0.05). The level of liver glycogen, muscle glycogen and fumaric reductase of model control group were lower than untreated group and high dose group (P < 0.05)., Conclusion: At the experimental conditions, ginsenosides solution of 250 mg/kg can improve the tolerance of rats in fatigue campaign and have the function of anti-fatigue.

Mammalian type I IFNs (IFN-Is) mediate their potent biological activities through an evolutionarily conserved IFN-alpha receptor (IFNAR), consisting of IFNAR1 and IFNAR2. These two chains direct the rapid activation of two founding members of the STAT family of transcription factors, STAT1 and STAT2. To understand how IFN-Is direct the recruitment and activation of STATs, a series of mutant murine IFNAR1 and IFNAR2 receptors were generated and evaluated in IFNAR1 and IFNAR2 knockout cells. These studies reveal that a single conserved IFNAR2 tyrosine, Y(510), plays a critical role in directing the IFN-I-dependent activation of STAT1 and STAT2, both in murine fibroblasts and macrophages. A second IFNAR2 tyrosine, Y(335), plays a more minor role. Likewise, Y(510) > Y(335) play a critical role in the induction of genes and antiviral activity traditionally associated with IFN-Is.

In recent years, adenoviruses that selectively replicate in tumor cells have been developed. However, there is a tremendous need to improve their anticancer efficacy. We wish to investigate whether a strategy that combines the oncolytic effects of an adenoviral vector with simultaneous expression of soluble form of transforming growth factor-beta type II receptor (sTGFbetaRII) offers a therapeutic advantage. We chose to target TGF-betas because they play a pivotal role in late-stage tumorigenesis by enhancing tumor invasion and metastasis. A sTGFbetaRII cDNA was cloned in conditionally replicating adenoviral vector rAd-sTRII and in a replication-deficient adenovirus Ad-sTRII. Infection of MDA-MB-231 breast cancer cells with rAd-sTRII or Ad-sTRII followed by Western blot analysis indicated the expression of diffused glycosylated forms of sTGFbetaRII that were also secreted into the extracellular medium. The secreted proteins were shown to bind with TGF-beta and antagonize TGF-beta-induced p38 mitogen-activated protein kinase activity. However, marked differences in the replication potential of rAd-sTRII and Ad-sTRII were observed in breast tumor cells. Infection of MDA-MB-231 cells with rAd-sTRII resulted in cytotoxicity and significant increase in the adenoviral titers that were comparable with a wild-type adenovirus dl309. However, Ad-sTRII was much less toxic to the tumor cells, and the viral titers of Ad-sTRII remained relatively unchanged. These results suggest that the infection of breast tumor cells with conditionally replicating adenoviral vector rAd-sTRII produced sTGFbetaRII that can abrogate TGF-beta signaling while maintaining the replication potential of the virus, indicating that rAd-sTRII could be a potential anticancer agent.

As most solid tumors are hypoxic, dendritic cells (DC) in solid tumors are also exposed to hypoxia. While many adaptation responses of tumor cells to hypoxia are known, it is yet to be determined how hypoxia affects the functions of DC. To explore the effects of hypoxia on the functions of DC, we compared the expression of surface markers, cytokines, chemokine receptors and matrix metalloproteinases (MMP) of human monocyte-derived DC (hmDC) differentiated under hypoxia to those differentiated under normoxia. Both groups of hmDC expressed similar levels of surface markers and cytokines. However, expression of MMP-9 and membrane type-1-MMP, as well as migrating activity, was significantly suppressed in hmDC differentiated under hypoxia compared with their normoxia counterparts. We also demonstrated that trichostatin A restored the production of MMP-9 in hmDC, under hypoxia. Collectively, our findings show that a hypoxic microenvironment suppresses the production of MMP in hmDC, most probably through the deacetylation of promoter regions of MMP, thus suppressing the migrating activity of hmDC. Our results suggest that the hypoxic microenvironment in solid tumor tissues may suppress the function of DC.

Transforming growth factor (TGF) betas are multifunctional polypeptides that regulate several cellular functions, including cell growth and differentiation, extra cellular matrix production, motility and immunosuppression. The growth-inhibiting properties of TGFbeta have gained much attention into its role as a tumor suppressor. There is, however, now increasing evidence that TGFbeta switches roles, from tumor suppressor to tumor promoter, as the tumor progresses. Given the integral role of TGFbeta in the tumor progression, it follows that TGFbeta signaling offers an attractive target for cancer therapy. Several strategies including the use of antisense oligonucleotides for TGFbeta, TGFbeta antibodies, dominant negative TGFbeta receptor II, and small drug-molecules to inhibit TGFbeta receptor I kinase have shown great promise in the preclinical studies. These new findings, coupled with progressing clinical trials indicate that inhibition of TGFbeta signaling may, indeed, be a viable option to cancer therapy. This review summarizes the TGFbeta signaling, the dual role of TGFbeta--as a tumor suppressor and tumor promoter, and various strategies targeted against TGFbeta signaling for cancer therapy. The next few years promise to better our understanding of approaching cancer therapy with an eye to the inhibition of TGFbeta signaling.

We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors.

Objective: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future., Methods: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T-cell cytotoxicity was measured by (MTT) assay., Results: CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic-phase CML. Group A of serum-free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum-free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class II antigen on the surface of DCs was notable (> 50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10% - 50%). Although CD1a(+)/CD14(-) DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27.2 fold at DCs: T cells ratio of 1:10). At day 12, CD1a(+) cells from three patients were studied by displaying G banding and Ph(+) cells in these populations were 100%, 98% and 60%, respectively. At an effector: target ratio of 40:1, 32% to 45% cytotoxicity was noted with DC-stimulated T cells against autologous leukemia cells., Conclusions: A stable serum-free culture system of CML-DCs was established. The expression of CD83 and CD86 on the surface of CML-DCs and DCs' potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti-leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.