Publications by authors named "Li Qiu"

630 Publications

Alterations in Gut Vitamin and Amino Acid Metabolism are Associated with Symptoms and Neurodevelopment in Children with Autism Spectrum Disorder.

J Autism Dev Disord 2021 Jul 14. Epub 2021 Jul 14.

Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Childhood Nutrition and Health, Chongqing, 400014, China.

Metabolic disturbance may be implicated in the pathogenesis of autism. This study aimed to investigate the gut metabolomic profiles of autistic children and to analyze potential interaction between gut metabolites with autistic symptoms and neurodevelopment levels. We involved 120 autistic and 60 neurotypical children. Autistic symptoms and neurodevelopment levels were assessed. Fecal samples were analyzed using untargeted liquid chromatography-tandem mass spectrometry methods. Our results showed the metabolic disturbances of autistic children involved in multiple vitamin and amino acid metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine-methionine metabolism, and vitamin digestion and absorption. Differential gut metabolites were correlated to autistic symptoms and neurodevelopment levels. Our findings improved the understanding of the perturbations of metabolome networks in autism.
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http://dx.doi.org/10.1007/s10803-021-05066-wDOI Listing
July 2021

Homology and Immune Checkpoint Dual-Targeted Sonocatalytic Nanoagents for Enhancing Sonodynamic Tumor Therapy.

ACS Appl Mater Interfaces 2021 Jul 7;13(28):32810-32822. Epub 2021 Jul 7.

Department of Ultrasound, National Clinical Research Center for Geriatrics, West China Hospital, College of Polymer Science and Engineering, Sichuan University, Chengdu 610041, China.

Sonocatalytic nanoagents (SCNs), a kind of sonosensitizers, could catalyze oxygen to generate abundant reactive oxygen species (ROS) under stimulations of noninvasive and deep-penetrating ultrasound (US), which is commonly used for sonodynamic therapy (SDT) of tumors such as malignant melanoma. However, poor bioavailability of most SCNs and fast quenching of extracellular-generating ROS from SDT limit further applications of SCNs in the SDT of tumors. Herein, we synthesized a new kind of TiO-based SCN functionalized with the malignant melanoma cell membrane (B16F10M) and programmed cell death-ligand 1 antibody (aPD-L1) for homology and immune checkpoint dual-targeted and enhanced sonodynamic tumor therapy. Under US irradiation, the synthesized SCN can catalytically generate a large amount of O. In vitro experiments validate that functionalized SCNs exhibit precise targeting effects, high tumor cell uptake, and intracellular sonocatalytic killing of the B16F10 cells by a large amount of localized ROS. Utilizing the melanoma animal model, the functionalized SCN displays visible long-term retention in the tumor area, which assists the homology and immune checkpoint synergistically dual-targeted and enhanced in vivo SDT of the tumor. We suggest that this highly bioavailable and dual-functionalized SCN may provide a promising strategy and nanoplatform for enhancing sonodynamic tumor therapies.
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http://dx.doi.org/10.1021/acsami.1c08105DOI Listing
July 2021

4,7-Disubstituted 7-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus.

Molecules 2021 Jun 22;26(13). Epub 2021 Jun 22.

Center for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.

Discovery of compound as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9-purine or 1-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7-pyrrolo[2,3-d]pyrimidines and their analogs including compounds , and as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.
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http://dx.doi.org/10.3390/molecules26133779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270260PMC
June 2021

Relationship between Tumor Necrosis Factor-Alpha and Neuropeptide Y Expression and Neurological Function Score in Epileptic Children.

Iran J Public Health 2021 May;50(5):1056-1064

Department of Neurology (II), Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, 221006, P.R.China.

Background: To observe the relationship between Tumor Necrosis Factor-alpha (TNF-α) and Neuropeptide Y (NPY) expression and neurological function score in epileptic children.

Methods: Fifty-four epileptic children diagnosed and treated in Xuzhou Children's Hospital, China from Feb 2017 to Mar 2018 were collected and included in a research group (RG), while 30 healthy children who underwent physical examination at the same time were included in the control group (CG). ELISA was used to detect the expression of TNF-α and NPY in the serum of children in the two groups, and those before treatment were compared. The National Institute of Health stroke scale (NIHSS) and Hamilton Anxiety (HAMA) scores before and after treatment were observed, and Pearson correlation was used to analyze the relationship between the expression levels of TNF-α and NPY in the serum as well as NIHSS and HAMA scores.

Results: The expression levels of TNF-α and NPY in the serum of children in the RG were significantly higher than those in the CG (<0.001). The expression level of TNF-α was positively correlated with the NIHSS and HAMA scores (r=0.748, <0.001) (r=0.772, <0.001). The expression level of NPY was positively correlated with the NIHSS and HAMA scores (r=0.768, <0.001) (r=0.643, <0.001).

Conclusion: TNF-α and NPY are highly expressed in epileptic children and are positively correlated with neurological function score.
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http://dx.doi.org/10.18502/ijph.v50i5.6123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223571PMC
May 2021

The role of non-apoptotic cell death in the treatment and drug-resistance of digestive tumors.

Exp Cell Res 2021 Jun 23;405(2):112678. Epub 2021 Jun 23.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China; West China Biomedical Big Data Center, Sichuan University, No. 37, GuoXue Xiang Chengdu, Sichuan, China. Electronic address:

Tumor cell apoptosis evasion is one of the main reasons for easy metastasis occurrence, chemotherapy resistance, and the low five-year survival rate of digestive system tumors. Current research has shown that non-apoptotic cell death plays an important role in tumors of the digestive system. Therefore, increasing the proportion of non-apoptotic tumor cells is one of the effective methods of improving therapeutic efficacies for digestive system tumors. Non-apoptotic cell death modes mainly include autophagic cell death, pyroptosis, ferroptosis, in addition to other cell death modes. This review covers a systematic review relating to the research progress made into autophagic cell death, pyroptosis, ferroptosis, and other cell death modes in the treatment of digestive system tumors. It also highlights how treatment is a reasonable prospect based on clinical experience and provides reliable guidance for the further development of digestive system tumor treatments.
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http://dx.doi.org/10.1016/j.yexcr.2021.112678DOI Listing
June 2021

Design, synthesis and antiproliferative activity of novel 2,4-diamino-5-methyleneaminopyrimidine derivatives as potential anticancer agents.

Bioorg Med Chem Lett 2021 Jun 19;47:128213. Epub 2021 Jun 19.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

In order to discover new anticancer agents, 25 novel 2,4-diamino-5-methyleneaminopyrimidine derivatives were designed and synthesized based on our previous work via a ring-opening strategy. Among them, compared with 5-FU, compound 7i exhibited 4.9-, 2.9-, 2.1-, and 3.0-fold improvement in inhibiting HCT116, HT-29, MCF-7, and HeLa cells proliferation with IC values of 4.93, 5.57, 8.84, and 14.16 μM, respectively. Moreover, further mechanistic studies indicated that compound 7i could concentration-dependently induce cell cycle arrest and apoptosis in HCT116 cells. These findings revealed that 2,4-diamino-5-methyleneaminopyrimidine scaffold has potential for further investigation to explore novel anticancer agents.
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http://dx.doi.org/10.1016/j.bmcl.2021.128213DOI Listing
June 2021

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

Lancet Oncol 2021 07 15;22(7):977-990. Epub 2021 Jun 15.

Live Surgery Ward, Peking Union Medical College Hospital, Beijing, China.

Background: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma.

Methods: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes.

Findings: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause).

Interpretation: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.

Funding: Innovent Biologics.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00252-7DOI Listing
July 2021

Molecular Doping Directed by a Neutral Radical.

ACS Appl Mater Interfaces 2021 Jun 16. Epub 2021 Jun 16.

Zernike Institute of Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.

Molecular doping makes possible tunable electronic properties of organic semiconductors, yet a lack of control of the doping process narrows its scope for advancing organic electronics. Here, we demonstrate that the molecular doping process can be improved by introducing a neutral radical molecule, namely nitroxyl radical (2,2,6,6-teramethylpiperidin-i-yl) oxyl (TEMPO). Fullerene derivatives are used as the host and 1,3-dimethyl-2-phenyl-2,3-dihydro-1-benzo[d]imidazoles (DMBI-H) as the n-type dopant. TEMPO can abstract a hydrogen atom from DMBI-H and transform the latter into a much stronger reducing agent DMBI, which efficiently dopes the fullerene derivative to yield an electrical conductivity of 4.4 S cm. However, without TEMPO, the fullerene derivative is only weakly doped likely by a hydride transfer following by an inefficient electron transfer. This work unambiguously identifies the doping pathway in fullerene derivative/DMBI-H systems in the presence of TEMPO as the transfer of a hydrogen atom accompanied by electron transfer. In the absence of TEMPO, the doping process inevitably leads to the formation of less symmetrical hydrogenated fullerene derivative anions or radicals, which adversely affect the molecular packing. By adding TEMPO we can exclude the formation of such species and, thus, improve charge transport. In addition, a lower temperature is sufficient to meet an efficient doping process in the presence of TEMPO. Thereby, we provide an extra control of the doping process, enabling enhanced thermoelectric performance at a low processing temperature.
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http://dx.doi.org/10.1021/acsami.1c03411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251695PMC
June 2021

Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist.

J Med Chem 2021 Jun 14;64(12):8775-8797. Epub 2021 Jun 14.

Guangdong Provincial Key Laboratory of Biocomputing, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.

Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound (designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC) value of 64 nM and showed excellent selectivity against other nuclear receptors. also potently suppressed cell proliferation, colony formation, and the expression of androgen receptor (AR)-regulated genes in AR-positive prostate cancer cell lines. In addition, demonstrated good metabolic stability and a pharmacokinetic property with reasonable oral bioavailability (32.41%) and moderate half-life ( = 4.98 h). Significantly, oral administration of compound achieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound may serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00763DOI Listing
June 2021

Pd-Single-Atom Coordinated Biocatalysts for Chem-/Sono-/Photo-Trimodal Tumor Therapies.

Adv Mater 2021 Jul 6;33(29):e2101095. Epub 2021 Jun 6.

Department of Ultrasound, National Clinical Research Center for Geriatrics, West China Hospital, College of Polymer Science and Engineering, Sichuan University, Chengdu, 610041, China.

The diversity, complexity, and heterogeneity of malignant tumor seriously undermine the efficiency of mono-modal treatment. Recently, multi-modal therapeutics with enhanced antitumor efficiencies have attracted increasing attention. However, designing a nanotherapeutic platform with uniform morphology in nanoscale that integrates with efficient chem-/sono-/photo-trimodal tumor therapies is still a great challenge. Here, new and facile Pd-single-atom coordinated porphyrin-based polymeric networks as biocatalysts, namely, Pd-Pta/Por, for chem-/sono-/photo-trimodal tumor therapies are designed. The atomic morphology and chemical structure analysis prove that the biocatalyst consists of atomic Pd-N coordination networks with a Pd-N -Cl catalytic center. The characterization of peroxidase-like catalytic activities displays that the Pd-Pta/Por can generate abundant •OH radicals for chemodynamic therapies. The ultrasound irradiation or laser excitation can significantly boost the catalytic production of O by the porphyrin-based sono-/photosensitizers to achieve combined sono-/photodynamic therapies. The superior catalytic production of •OH is further verified by density functional theory calculation. Finally, the corresponding in vitro and in vivo experiments have demonstrated their synergistic chem-/sono-/photo-trimodal antitumor efficacies. It is believed that this study provides new promising single-atom-coordinated polymeric networks with highly efficient biocatalytic sites and synergistic trimodal therapeutic effects, which may inspire many new findings in reactive oxygen species-related biological applications across broad therapeutics and biomedical fields.
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http://dx.doi.org/10.1002/adma.202101095DOI Listing
July 2021

Significant Association Between XRCC1 Expression and Its rs25487 Polymorphism and Radiotherapy-Related Cancer Prognosis.

Front Oncol 2021 19;11:654784. Epub 2021 May 19.

Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Background/aims: XRCC1 (X-ray repair cross-complementing protein 1) expression and its single nucleotide polymorphism XRCC1 rs25487 (G>A) may be related to radiotherapy-related cancer prognosis or radiation-induced side effects. However, this association is controversial. We performed a bioinformatic analysis and a meta-analysis to obtain comprehensive results. TCGA data sets and eligible publications published before November 31, 2020 were retrieved by searching the PubMed, Web of Science and CNKI (China National Knowledge Infrastructure) databases. ORs (odds ratios) and HRs (hazard ratios) with their corresponding 95% CIs (confidence intervals) were calculated to evaluate associations. For XRCC1 single nucleotide polymorphisms, we employed three types of comparisons: GA vs GG, AA vs GG and GA+AA vs GG.

Results: Sixty nine articles with 10232 patients and 17 TCGA data sets with 2705 patients were included in the analysis. We observed that high XRCC1 expression was associated with an increased risk of minor treatment response and poor overall survival, XRCC1 rs25487 was associated with reduced risk of minor treatment response in esophageal cancer and an increased risk of high-grade side effects in head and neck cancer.

Conclusion: The results suggest that XRCC1 expression and rs25487 polymorphism are prognostic factors for patients receiving radiotherapy-related treatment. Considering the insufficient treatment parameters provided and the various sample sizes in most of the studies, we suggest that genetic association studies related to radiation-based treatment should include more cancer types with sufficient statistical power and more detailed clinical parameters.
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http://dx.doi.org/10.3389/fonc.2021.654784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170393PMC
May 2021

Antigenic Evolution on a Global Scale Reveals the Potential Natural Selection of Severe Acute Respiratory Syndrome-Coronavirus 2 by Pre-existing Cross-Reactive T-Cell Immunity.

Front Microbiol 2021 18;12:599562. Epub 2021 May 18.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has changed constantly during worldwide community transmission of this virus. However, the reasons for the changes in mutation patterns are still unclear. Accordingly, in this study, we present a comprehensive analysis of over 300 million peptides derived from 13,432 SARS-CoV-2 strains harboring 4,420 amino acid mutations to analyze the potential selective pressure of the host immune system and reveal the driver of mutations in circulating SARS-CoV-2 isolates. The results showed that the nonstructural protein ORF1ab and the structural protein Spike were most susceptible to mutations. Furthermore, mutations in cross-reactive T-cell epitopes between SARS-CoV-2 and seasonal human coronavirus may help SARS-CoV-2 to escape cellular immunity under long-term and large-scale community transmission. Additionally, through homology modeling and protein docking, mutations in Spike protein may enhance the ability of SARS-CoV-2 to invade host cells and escape antibody-mediated B-cell immunity. Our research provided insights into the potential mutation patterns of SARS-CoV-2 under natural selection, improved our understanding of the evolution of the virus, and established important guidance for potential vaccine design.
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http://dx.doi.org/10.3389/fmicb.2021.599562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169977PMC
May 2021

Development of Measurement Equipment and Experimental and Numerical Simulation Studies for Warm Forming Limits of High-Strength Steel.

Materials (Basel) 2021 May 2;14(9). Epub 2021 May 2.

State Key Laboratory for Manufacturing Systems Engineering, School of Mechanical Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

This paper describes the research and development of a set of measurement equipment for the warm forming limits of high-strength steel based on the Nakazima bulging test method and the digital image correlation method. The equipment could provide an argon shield and a water-cooling atmosphere, as well as two heating options: heating the specimen, dies, and environment to the test temperature simultaneously or heating the specimen to the test temperature at a higher speed than that for the dies and environment. The equipment was applied to measure the forming limit curves for high-strength DP600 steel at room temperature and at the temperature of 300 °C to verify its performance. The DYNAFORM software was then applied for the digital simulation of the bulging test method. A new limit-strain-fitting method was proposed to eliminate the impact of the distorted grid on the digital simulation process. The change trend of the forming limit curve acquired in the test had sound consistency with the test results.
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http://dx.doi.org/10.3390/ma14092373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124573PMC
May 2021

Serum Folate Status Is Primarily Associated With Neurodevelopment in Children With Autism Spectrum Disorders Aged Three and Under-A Multi-Center Study in China.

Front Nutr 2021 13;8:661223. Epub 2021 May 13.

Chongqing Key Laboratory of Childhood Nutrition and Health, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing, China.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Folate has been demonstrated to be associated with ASD. However, current studies on the correlation between folate and symptoms of children with ASD have inconsistent conclusions, use mainly small samples, and lack age-stratified analysis. This study aimed to explore the association between serum folate and symptoms of autistic children at different age groups from a multi-center perspective. We enrolled 1,300 children with ASD and 1,246 typically developing (TD) children under 7 years old from 13 cities in China. The Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS) were used to evaluate the symptoms of children with ASD. China neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016) scale was used to evaluate the neurodevelopment of children with ASD. Serum folate was measured by chemiluminescence assay in the two groups. The serum folate levels of children with ASD were lower than that of TD children. In terms of core symptoms of ASD, we found that the serum folate levels were not associated with ABC, SRS, and CARS scores in ASD children of all ages but negatively associated with communication warning behavior scores of CNBS-R2016 in ASD children aged three and under. Concerning development quotients, it was at the age of three and under that serum folate levels were positively associated with gross motor, fine motor, language, and general quotient of ASD children. These ASD children aged three and under were further divided into two groups according to the median of serum folate (14.33 ng/mL); we found that compared to ASD children with folate ≤ 14.33 ng/mL, those with folate >14.33 ng/mL had lower communication warning behavior score and higher gross motor, fine motor, adaptive behavior, language, person-social, and general development quotients. We found that serum folate status was primarily associated with the neurodevelopment of children with ASD aged three and under. Furthermore, relatively higher serum folate levels may be more beneficial for children with ASD. Our results suggest that folate level should be paid more attention in ASD children, especially in early life, to better promote the intervention of ASD children.
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http://dx.doi.org/10.3389/fnut.2021.661223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155683PMC
May 2021

Controlling n-Type Molecular Doping Regiochemistry and Polarity of Pendant Groups on Low Band Gap Donor-Acceptor Copolymers.

Macromolecules 2021 Apr 8;54(8):3886-3896. Epub 2021 Apr 8.

Stratingh Institute for Chemistry, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands.

We demonstrate the impact of the type and position of pendant groups on the n-doping of low-band gap donor-acceptor (D-A) copolymers. Polar glycol ether groups simultaneously increase the electron affinities of D-A copolymers and improve the host/dopant miscibility compared to nonpolar alkyl groups, improving the doping efficiency by a factor of over 40. The bulk mobility of the doped films increases with the fraction of polar groups, leading to a best conductivity of 0.08 S cm and power factor (PF) of 0.24 μW m K in the doped copolymer with the polar pendant groups on both the D and A moieties. We used spatially resolved absorption spectroscopy to relate commensurate morphological changes to the dispersion of dopants and to the relative local doping efficiency, demonstrating a direct relationship between the morphology of the polymer phase, the solvation of the molecular dopant, and the electrical properties of doped films. Our work offers fundamental new insights into the influence of the physical properties of pendant chains on the molecular doping process, which should be generalizable to any molecularly doped polymer films.
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http://dx.doi.org/10.1021/acs.macromol.1c00317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154869PMC
April 2021

Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 Jul 8;6(7):559-568. Epub 2021 May 8.

Department of Intervention, Fujian Cancer Hospital, Fuzhou, China.

Background: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.

Methods: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860.

Findings: Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators.

Interpretation: Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile.

Funding: Jiangsu Hengrui Medicine.
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http://dx.doi.org/10.1016/S2468-1253(21)00109-6DOI Listing
July 2021

First-line therapy of bevacizumab plus chemotherapy versus cetuximab plus chemotherapy for metastatic colorectal cancer patients with mucinous adenocarcinoma or mucinous component.

Cancer Med 2021 05 3;10(10):3388-3402. Epub 2021 May 3.

Department of Abdominal Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.

Background: To compare the efficacy of first-line bevacizumab plus chemotherapy with cetuximab plus chemotherapy based on the stratification of metastatic colorectal cancer (mCRC) patients with mucinous adenocarcinoma (MA) or mucinous component (MC).

Methods: A retrospective study involving all mCRC patients receiving first-line bevacizumab-based or cetuximab-based chemotherapy at our hospital from September 2013 to January 2020 was conducted. Overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were compared between the cetuximab-chemotherapy group and the bevacizumab-chemotherapy group on the basis of the conventional pathological classification of MA or MC.

Results: A total of 620 patients with mCRC were included in our study, consisting of 141 (22.7%) patients with MA/MC and 479 (77.3%) patients with non-mucinous adenocarcinoma (NMA). In the MA/MC cohort, patients who were treated with bevacizumab-based chemotherapy were associated with significantly better OS than those treated with cetuximab-base chemotherapy (30.0 vs. 26.3 months, p = 0.002), irrespective of tumor sites. The efficacy of bevacizumab-based chemotherapy was higher in nearly all subgroups as shown in the subgroup analysis. In the NMA cohort, median OS was better in the cetuximab plus chemotherapy group than that in the bevacizumab plus chemotherapy group (32.2 vs. 27.0 months, p = 0.005) for left-side mCRC patients, whereas OS was significantly longer in the bevacizumab plus chemotherapy group for right-side mCRC patients (26.0 vs. 20.9 months, p = 0.013).

Conclusion: Conventional pathological classification (e.g. MA/MC) should be considered when tailoring the individualized optimal treatment for mCRC. Bevacizumab plus chemotherapy as first-line therapy may be the optimal option for patients with MA/MC.
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http://dx.doi.org/10.1002/cam4.3876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124114PMC
May 2021

Ratiometric fluorescence detection of sulfide ions based on lanthanide coordination polymer using guanosine diphosphate as ligand.

Colloids Surf B Biointerfaces 2021 Aug 28;204:111796. Epub 2021 Apr 28.

Jiangxi Key Laboratory of Industrial Ceramics, College of Materials and Chemical Engineering, Pingxiang University, Pingxiang, 337055, China.

The efficiency of energy transfer from guanine nucleotide to terbium ion (Tb) is affected by the phosphate group significantly. Compared with the biomolecules 5'-GMP (guanosine monophosphate), guanosine diphosphate (GDP) exhibits better sensitize ability to Tb ions luminescence. Assisted with the carboxycoumarin ligand, we synthesized a more stable optical [email protected] polymer with the characteristic emission peaks located on 440 nm and 545 nm in this work. The [email protected] polymer is not only rich in metal binding sites, but also maintains a moderate ionic binding force, which helps metal ions to bind or leave it easily. Experiment result shows that [email protected] polymer has the appropriate binding force for Fe ions, which can be destroyed by sulfur ions (S) as the formation of FeS precipitation. Based on this, [email protected] was designed as the ratio fluorescence probe for sulfur ions detection, where the fluorescence at 545 nm can be selectively quenched by Fe ions, while that at 440 nm was unaffected, in the presence of S ions, the quenched fluorescence can be recovered remarkably. With the increasing S ions from 0.1-45 μM, the ratio of fluorescence intensity at 545 nm to 440 nm (F/F) is linear to S concentration, and the detection limit of S was calculated to be 0.073 μM. Contrast to those fluorescence probes with single wavelength emission, [email protected] displays a comparable sensitivity, the introduced self-adjust wavelength improved the detection accuracy efficiently. The above 98.1 % recovery rates of S ions in the actual water sample demonstrated the practicability of [email protected] fluorescence probe.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111796DOI Listing
August 2021

[Cathepsin-B involved in effect of electroacupuncture by inhibiting the activation of NLRP3 inflammasome in rats with acute gouty arthritis].

Zhen Ci Yan Jiu 2021 Apr;46(4):295-300

College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016,China.

Objective: To observe the effect of electroacupuncture (EA) on Cathepsin-B in the synovium of the knee joint of acute gouty arthritis(AGA) rats, so as to explore the mechanism of EA in the treatment of AGA.

Methods: A total of 60 male Wistar rats were randomly divided into normal control,model, medication and EA groups, with 15 rats in each group. Rat model of AGA was established by injection of 0.2 mL sodium urate crystal suspension into the left knee joint cavity. The rats in the medication group were treated with colchicine by gavage(0.3 mg·kg·d), and the rats in the EA group were treated with EA at the left "Sanyinjiao" (SP6) and "Zusanli"(ST36) for 10 min each time, once a day for a week. The Coderre gait grading standard was used to score the gait of rats. The pathological morphology of synovial tissue of the left knee joint was observed by H.E. staining. The expression levels of Cathepsin-B protein and Nod-like receptor pyrin domain 3(NLRP3), apoptosis-associated speck-like protein containing CARD (ASC),Caspase-1, interleukin-1β(IL-1β) and IL-18 mRNAs were detected by Western blot and real-time fluorescence quantitative PCR, respectively.

Results: Compared with the normal control group, the degree of synovitis infiltration in the model group was more serious. And the gait score,the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3,ASC,Caspase-1, IL-1β,IL-18 were significantly increased (<0.01).After the interventions, the degree of inflammatory infiltration was mild, The gait score, the protein expression level of Cathepsin-B and the mRNA expression levels of NLRP3 and ASC,Caspase-1,IL-1β,IL-18 were significantly decreased in both medication and EA groups in contrast to the model group (<0.01, <0.05). Compared with medication group, the mRNA expression levels of Caspase-1 and IL-18 in the EA group were increased (<0.05).

Conclusion: EA may inhibit the activation of NLRP3 inflammasome by reducing the activity of Cathepsin-B in the synovium of the knee joint, so as to treat AGA.
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http://dx.doi.org/10.13702/j.1000-0607.200240DOI Listing
April 2021

A rare case with compound heterozygous mutations of piezo-type mechanosensitive ion channel component 2 (PIEZO2) induced tracheobronchomalacia.

Chin Med J (Engl) 2021 04 29;134(10):1254-1256. Epub 2021 Apr 29.

Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

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http://dx.doi.org/10.1097/CM9.0000000000001500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143733PMC
April 2021

Bevacizumab Combined with S-1 and Raltitrexed for Patients with Metastatic Colorectal Cancer Refractory to Standard Therapies: A Phase II Study.

Oncologist 2021 Apr 8. Epub 2021 Apr 8.

Department of Abdominal Cancer, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China.

Lessons Learned: Bevacizumab combined with S-1 and raltitrexed demonstrated positive antitumor efficacy and acceptable toxicity. This combination might represent a treatment option for refractory metastatic colorectal cancer.

Background: In patients with metastatic colorectal cancer (mCRC) refractory to standard therapies, S-1 plus raltitrexed showed a good objective response rate (ORR) and significant survival benefit in our previous study. In the present study, we assessed the activity and safety of bevacizumab combined with S-1 and raltitrexed.

Methods: This investigator-initiated, open-label, single-arm, phase II trial was performed at West China Hospital in China. Patients with mCRC who had disease progression after fluoropyrimidine, irinotecan, and oxaliplatin and had at least one measurable lesion were eligible for this trial. Anti-epidermal growth factor receptor (EGFR) (for tumors with wild-type RAS) and anti-vascular endothelial growth factor (VEGF) therapy in the first or second line was allowed, but patients who had been treated with bevacizumab across two consecutive chemotherapy regimens were excluded. Patients received bevacizumab (7.5 mg/kg on day 1), oral S-1 (80-120 mg per day for 14 days), and raltitrexed (3 mg/m on day 1) every 3 weeks. The primary endpoint was ORR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.

Results: From September 2015 to November 2019, 44 patients were enrolled. Tumor response evaluation was available in 44 patients at the time of the analysis. There were no complete responses; the ORR was 15.9%, and the disease control rate was 54.5%. Median PFS and OS were 110 days (95% confidence interval [CI], 65.0-155.0) and 367 days (95% CI, 310.4-423.6), respectively. The combination was well tolerated.

Conclusion: Bevacizumab combined with S-1 and raltitrexed showed promising antitumor activity and safety in refractory mCRC.
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http://dx.doi.org/10.1002/onco.13778DOI Listing
April 2021

Prevalence and genotype distribution of HPV infection among 214,715 women from Southern China, 2012-2018: baseline measures prior to mass HPV vaccination.

BMC Infect Dis 2021 Apr 7;21(1):328. Epub 2021 Apr 7.

The First School of Clinical Medicine, Southern Medical University, Chenzhou NO.1 People's Hospital, Chenzhou, 423000, P.R. China.

Background: The epidemiology on the human papillomavirus (HPV) among females in Southern China is not well-established. Baseline data on the prevalence of HPV infection in China prior to mass prophylactic HPV vaccination would be useful. Thus, this study aims to determine the type-specific HPV prevalence and distribution among females from Southern China prior to mass HPV vaccination.

Methods: A retrospective cross-sectional study employing 214,715 women attending ChenZhou NO.1 People's Hospital for cervical screening during 2012-2018 was conducted prior to widespread HPV vaccination. HPV genotype was detected using nucleic acid molecular diversion hybridization tests. The overall prevalence, age-specific prevalence, type distribution, and annual trend were analyzed.

Results: The overall HPV prevalence was 18.71% (95% confidence interval [CI], 18.55-18.88%) among Southern China females. During 2012-2018, the prevalence of HPV infection showed a downward tendency, from 21.63% (95% CI, 21.07-22.20%) in 2012 to 18.75% (95% CI, 18.35-19.16%) in 2018. Age-specific HPV distribution displayed a peak at young women aged less than 21 years (33.11, 95% CI, 31.13-35.15%), 20.07% (95% CI, 19.70-20.44%) among women aged 21-30 years, 17.29% (95% CI, 17.01-17.57%) among women aged 31-40 years, 17.23% (95% CI, 16.95-17.51%) among women aged 41-50 years, 21.65% (95% CI, 21.11-22.20%) among women aged 51-60 years, and 25.95% (95% CI, 24.86-27.07%) among women aged over 60 years. Of the 21 subtypes identified, the top three prevalent high-risk HPV (HR-HPV) genotypes were HPV52 (5.12%; 95% CI, 21.11-22.20%), - 16 (2.96%; 95% CI, 2.89-3.03%), and - 58 (2.51%; 95% CI, 2.44-2.58%); the predominant low-risk HPV (LR-HPV) genotypes were HPV81 (1.86%; 95%CI, 1.80-1.92%) and - 6 (0.69%; 95% CI, 0.66-0.73%) respectively. Incidence of HR-HPV only, LR-HPV only and mixed LR- and HR-HPV were 15.17, 2.07 and 1.47% respectively. Besides, single HPV infection accounted for 77.30% of all positive cases in this study.

Conclusions: This study highlights 1) a high prevalence of HPV infection among females with a decreasing tendency towards 2012-2018, especially for young women under the age of 21 prior to mass HPV vaccination; 2) HPV52, - 16 and - 58 were the predominant HPV genotypes, suggesting potential use of HPV vaccine covering these HPV genotypes in Southern China.
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http://dx.doi.org/10.1186/s12879-021-06019-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028771PMC
April 2021

Analysis of Mechanical Characteristics of Bionic Artificial Skin Using Different Suturing Patterns.

Appl Bionics Biomech 2021 20;2021:6696612. Epub 2021 Mar 20.

Tianjin Key Lab of High Speed Cutting and Precision Machining, Tianjin University of Technology and Education, China 300222.

Artificial bionic skin material is playing an increasingly important role in the field of medicine and bionic engineering and becoming a research hotspot in many disciplines in recent years. In this work, the digital moiré method was used to measure the mechanical field of the bionic skin material under different suturing conditions. Through the digital image process, the deformation characteristics and the stress distribution near the contact area between the bionic skin material and the suture were obtained and discussed. The different healing effects caused by suturing mode were further explored, which can provide mechanical guidance for wound suturing in clinical medicine.
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http://dx.doi.org/10.1155/2021/6696612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007379PMC
March 2021

Renal Injury by SARS-CoV-2 Infection: A Systematic Review.

Kidney Dis (Basel) 2021 Mar 16;7(2):100-110. Epub 2020 Nov 16.

Centre for Lipid Research and Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Background: SARS-CoV-2 infection can cause renal involvement, and severe renal dysfunction is more common among patients with chronic comorbid conditions, especially patients with chronic kidney disease. Angiotensin-converting enzyme 2 (ACE2) has been proven to be the major receptor of SARS-CoV-2 in kidneys, suggesting that ACE2-related changes may be involved in renal injury during the infection. In this review, we systematically reviewed the literature to summarize findings on the mechanism of renal injury caused by SARS-COV-2 infection, in order to provide a theoretical basis for renal protection therapy.

Summary: For patients with SARS-CoV-2 infection, renal injury mainly manifests as increased serum creatinine, variable degrees of proteinuria and hematuria, and radiographic abnormalities of the kidneys. In this review, we summarize the pathogenesis of renal injury deriving from SARS-CoV-2 infection by focusing on its etiology, pathology, and clinical manifestations. The virus causes kidney injury by either direct infection or systemic effects, including host immune clearance and immune tolerance disorders, endothelium-mediated vasculitis, thrombus formation, glucose and lipid metabolism disorder, and hypoxia.

Key Messages: Renal injury by SARS-CoV-2 is the result of multiple factors. Via highly expressed ACE2 in renal tissue, SARS-CoV-2 infection fundamentally initiates a mechanism of renal injury. Systemic effects such as host immune clearance and immune tolerance disorders, endothelial cell injury, thrombus formation, glucose and lipid metabolism disorder, and hypoxia aggravate this renal injury.
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http://dx.doi.org/10.1159/000512683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705946PMC
March 2021

Can Ga-PSMA-11 PET/CT predict pathological upgrading of prostate cancer from MRI-targeted biopsy to radical prostatectomy?

Eur J Nucl Med Mol Imaging 2021 Apr 4. Epub 2021 Apr 4.

Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China.

Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) is an ideal tool for staging and restaging of prostate cancer (PCa). This study was designed to investigate the prognostic role of preoperative Ga-PSMA-11 PET/CT in predicting pathological upgrading from multiparametric magnetic resonance imaging-targeted biopsy (mpMRI-TB) to final radical prostatectomy (RP) specimens in patients with localized PCa.

Methods: A total of 67 biopsy-confirmed localized PCa patients with mpMRI and Ga-PSMA-11 PET/CT prior to RP were included. Clinical and imaging characteristics derived from mpMRI and PET/CT were compared in patients with or without pathological upgrading. Predictors for pathological upgrading were evaluated by using univariate and multivariable analyses. A prediction model was developed based on the identified parameters and validated using internal validation.

Results: Pathological upgrading from mpMRI-TB to final RP specimens occurred in 38.8% (26/67) of the patients. Multivariable logistic regression analysis showed SUV (OR: 1.223, 95% CI 1.068-1.399, p = 0.003); highest tumor grade at mpMRI-TB, ISUP grade group (ISUP GG) 1 vs. 4 (OR: 0.11, 95% CI 0.000-0.452, p = 0.018) and ISUP GG 2 vs. 4 (OR: 0.16, 95% CI 0.001-0.252, p = 0.003); and multifocality on PET/CT (OR: 9.821, 95% CI 1.438-67.085, p = 0.02) were independent risk factors for pathological upgrading. Our developed prediction model based on the identified parameter showed good calibration at internal validation (mean absolute error = 0.033).

Conclusion: Ga-PSMA-11 PET/CT was found to be an ideal biomarker for the prediction of pathological upgrading from mpMRI-TB to RP, especially for patients with lower tumor grade at mpMRI-TB.
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http://dx.doi.org/10.1007/s00259-021-05217-2DOI Listing
April 2021

Ultrasound targeted microbubble destruction combined with Fe-MOF based bio-/enzyme-mimics nanoparticles for treating of cancer.

J Nanobiotechnology 2021 Mar 31;19(1):92. Epub 2021 Mar 31.

Department of Medical Ultrasound, Laboratory of Ultrasound Imaging Drug, West China Hospital of Sichuan University, Chengdu, 610041, China.

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http://dx.doi.org/10.1186/s12951-021-00835-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011114PMC
March 2021

The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer.

Front Oncol 2021 11;11:582040. Epub 2021 Mar 11.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, China.

Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.
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http://dx.doi.org/10.3389/fonc.2021.582040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991845PMC
March 2021

Novel SARS2 variants identified in a Chinese girl with HUPRA syndrome.

Mol Genet Genomic Med 2021 Apr 10;9(4):e1650. Epub 2021 Mar 10.

Department of Nephrology, Children's Hospital, Chongqing Medical University, Chongqing, China.

Background: Hyperuricemia, pulmonary hypertension, renal failure, and alkaline intoxication syndrome (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease. SARS2 gene encoding seryl-tRNA synthetase is the only pathogenic gene of HUPRA syndrome. All the previously reported cases with HUPRA syndrome were detected for homozygous mutation.

Methods: We identified compound heterozygous mutations causing HUPRA syndrome using whole-exome sequencing, and verifed pathogenicity with ACMG standards. All the previously published cases with SARS2 mutations were reviewed.

Results: SARS2 gene compound heterozygotes variants were detected in this Chinese patient (c.667G>A/c.1205G>A). Bioinformatics studies and protein models predict that a new variant (c.667G>A) is likely to be pathogenic. A total of six patients, five of whom were previously reported with HUPRA syndrome, were analyzed. All of the six had typical clinical manifestations of HUPRA syndrome, except the Chinese girl who had no pulmonary hypertension or alkaline intoxication. The shrunken kidney was more prominent in our proband. The average survival time for previously reported patients was 17 months, and the Chinese girl was 70 months. Three mutation variants were found, including five homozygous mutants, three of which were Palestinian (c.1169A > G), two of which were from a Spanish family (c.1205G> A), and one was a new variant (c.667G>A/c.1205G>A).

Conclusion: We found a new pathogenic form (compound heterozygous mutation) causing HUPRA syndrome, and identified a novel pathogenic site (c.667G>A) of the SARS2 gene, expanding the spectrum of SARS2 pathogenic variants. The mild phenotype in complex heterozygous mutations is described.
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http://dx.doi.org/10.1002/mgg3.1650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123761PMC
April 2021

Statin Use and Benefits of Thyroid Function: A Retrospective Cohort Study.

Front Endocrinol (Lausanne) 2021 2;12:578909. Epub 2021 Mar 2.

Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Purpose: Previous studies have suggested that cholesterol may influence thyroid function. Since statins are widely used for their cholesterol-lowering effect, we aimed to assess the association between statin use and thyroid function, and also to explore the role of the cholesterol-lowering effect in it.

Methods: We performed a retrospective cohort study derived from REACTION study. Eligible subjects receiving statin therapy were included in the statin group, and sex-, age-, total cholesterol (TC)-, and thyroid function-matched participants without lipid-lowering therapy were included in the control group. The median follow-up time was three years. Outcomes of thyroid function were evaluated at the end of follow-up. We used multivariable regression models to assess the association between statin use and outcomes of thyroid function, and also performed mediation analyses to explore the role of cholesterol in it.

Results: A total of 5,146 participants were screened, and 201 eligible subjects in the statin group and 201 well-matched subjects in the control group were analyzed. At the end of follow-up, TC and thyroid-stimulating hormone (TSH) levels in the statin group were lower than those in the control group (both p < 0.05), and the percentage of euthyroid subjects was higher in the statin group (88.06% vs. 76.12%, p = 0.002). The incidence rate of subclinical hypothyroidism (SCH) in euthyroid subjects was lower in the statin group (6.29% vs. 14.86%, p = 0.009), and the remission rate among subjects with SCH was higher in the statin group (50.00% vs. 15.38%, p = 0.008). In multivariable regression analyses, statin use was independently associated with lower TSH levels and higher odds to be euthyroid (OR 2.335, p = 0.004) at the end of follow-up. Mediation analyses showed the association between statin use and TSH levels were mediated by TC changes during follow-up.

Conclusion: Statin use was associated with benefits of thyroid function, and TC changes serve as a mediator of the association between statin use and TSH levels. Further studies are needed to clarify the possible underlying mechanism.
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http://dx.doi.org/10.3389/fendo.2021.578909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962670PMC
March 2021

Aqueous Extract of Bunge- Herb Pair Attenuates Osteoporosis in Ovariectomized Rats Through Suppressing Osteoclast Differentiation.

Front Pharmacol 2020 21;11:581049. Epub 2021 Jan 21.

School of Basic Medical Sciences, Qingdao University, Qingdao, China.

Traditional herb pair Bunge- (DG) owns various biological activities including anti-inflammatory and anti-oxidative stress. Oxidative stress is one high-risk factor for osteoporosis, then effect of DG on osteoporosis and underlying mechanisms was explored both and . Firstly, the predication from network pharmacology hinted that DG has the potential for ameliorating osteoporosis. Consistent with predication, DG significantly restored bone loss and deficiency of type II collagen, decreased TRAP and Cathepsin K positive areas in femur. Meanwhile it improved important characteristics of microarchitectural deterioration of tissue, reduced the numbers of NFATc1-positive osteoclast in the vertebra as well as decreased the serum osteoclast-specific cytokine RANKL and OPG release in OVX rats exhibiting its protective effect against osteoporosis. , DG noticeably decreased osteoclastic-special marker protein expressions of RANK, c-Fos and NFATc1. Furthermore, autophagy pathway p62/LC3B, ROS production and NF-κB were all activated by RANKL stimulation and blocked by DG pretreatment. Moreover, autophagy inhibitors, ROS scavenger, Ca chelator and NF-κB inhibitor remarkably suppressed c-Fos and NFATc1 expressions. Taken together, DG may ameliorate osteoporosis by regulating osteoclast differentiation mediated by autophagy and oxidative stress. This study provided a mechanistic basis for DG treating osteoporosis and offered a safe dose for DG in preventing and improving bone diseases.
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http://dx.doi.org/10.3389/fphar.2020.581049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941748PMC
January 2021