Publications by authors named "Yue Zhu"

472 Publications

An Atom-Economic Inverse Solid-Phase Peptide Synthesis Using Bn or BcM Esters of Amino Acids.

Org Lett 2021 Sep 17. Epub 2021 Sep 17.

School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, Hangzhou 310024, China.

An atom-economic N-to-C-directed solid-phase peptide synthesis is reported that uses benzyl (Bn) or (benzhydryl-carbamoyl)-methyl (BcM) esters of amino acids as the building blocks, which facilitate efficient hydrazinolysis, convenient conversion to acyl azide, and robust amidation with the next amino acid ester. This method is free of coupling reagents and free of protection on the side-chain OH, COH, CONH2, etc., therefore exhibiting a significantly improved atom economy compared to those of BOC- or Fmoc-based C-to-N-directed approaches.
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http://dx.doi.org/10.1021/acs.orglett.1c02769DOI Listing
September 2021

Isolation, structural characterization and bioactivities of polysaccharides from Laminaria japonica: A review.

Food Chem 2021 Sep 1;370:131010. Epub 2021 Sep 1.

National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Laminaria japonica is a familiar marine plant and is often used as food due to its abundant carbohydrates, vitamins and minerals. As one of the main types of active substances in L. japonica, polysaccharides are widely used in the food and chemical industries and in medicine and healthcare due to their health benefits, such as immunoregulatory, antioxidant, and antidiabetic effects. However, there has been no systematic summary of the isolation, structural characterization and bioactivities of L. japonica polysaccharides (LJPs). Therefore, the present review includes a survey of extraction and purification methods for these bioactive molecules, along with a dissertation on the structural characterization of the carbohydrate components. Moreover, an overview of the most recent results related to LJP biological activities is provided. This review provides a useful reference for further research, production, and application of LJPs in functional foods and therapeutic agents.
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http://dx.doi.org/10.1016/j.foodchem.2021.131010DOI Listing
September 2021

SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway.

Neoplasia 2021 Sep 9;23(10):1037-1047. Epub 2021 Sep 9.

Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

The E3 ubiquitin ligase adaptor Speckle-type POZ protein (SPOP) plays an important tumour suppressor role in prostate cancers (PCa), with mutation rate up to 15%. However, how SPOP mutations regulate prostate tumorigenesis remains elusive. Here, we report the identification of cell division cycle associated 5 (CDCA5) as a SPOP substrate. We found that SPOP interacts with CDCA5 and promotes its polyubiquitin degradation in a degron-dependent manner. This effect was greatly impaired by introducing PCa associated SPOP mutations. Importantly, we found that CDCA5 was essential for PCa cells to survive and proliferate. CDCA5 depletion in PCa cells led to cessation of proliferation, G2M arrest, severe sister chromatid aggregation disturbance, and apoptosis. we also found that CDCA5 knockdown decreased the protein expression of p-GSK3β, increased the activity of caspase-3, caspase-9, and the Bax/Bcl-2 ratio. Besides, we confirmed that CDCA5 interrupted cancer cell behavior via the AKT pathway. In contrast, silencing SPOP or overexpressing CDCA5 increased cell proliferation. Consistently, depleting SPOP along with CDCA5, or overexpressing CDCA5 along with SPOP also caused the growth of cells repressed. Consistent with the functional role of CDCA5, the mRNA and protein levels of CDCA5 were significantly increased in PCa, compared to normal tissues, and its high expression was associated with more severe lymph node metastasis, higher Gleason score, and poorer prognosis. Together, our data showed that SPOP plays a crucial role in inhibiting tumorigenesis and partly achieved this by promoting the degradation of oncoprotein CDCA5.
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http://dx.doi.org/10.1016/j.neo.2021.08.002DOI Listing
September 2021

hIgDFc-Ig inhibits B cell function by regulating the BCR-Syk-Btk-NF-κB signalling pathway in mice with collagen-induced arthritis.

Pharmacol Res 2021 Sep 6:105873. Epub 2021 Sep 6.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, Anhui Province, China; Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China; Anti-inflammatory Immune Drugs Collaborative Innovation Center, Anhui Province, Hefei, China. Electronic address:

Rheumatoid arthritis (RA) is an autoimmune disease targeting the synovium. Previous studies have found that IgD may be a potential target for the treatment of RA. We designed a new type of fusion protein, hIgDFc-Ig (DG), to block the binding of IgD to IgD receptor (IgDR). In this study, we found that DG has a significant therapeutic effect in mice with collagen-induced arthritis (CIA). DG improved the claw of irritation symptoms in these mice, inhibited the pathological changes in spleen and joint tissues, and had a moderating effect on B cell subsets at different inflammatory stages. Moreover, DG could also decrease the levels of IgA, IgD, IgM and IgG subtypes of immunoglobulin in the serum of mice with CIA. In vitro, B cell antigen receptor (BCR) knockout Ramos cells were established using the CRISPR/Cas9 technology to further study the activation of BCR signalling by IgD and the effect of DG. We found that the therapeutic effect of DG in mice with CIA may be achieved by inhibiting the activation of BCR signalling by IgD, which may be related to the activation of Igβ. In summary, DG may be a potential biological agent for the treatment of RA and it has broad application prospects in the future.
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http://dx.doi.org/10.1016/j.phrs.2021.105873DOI Listing
September 2021

Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.

PLoS Pathog 2021 Sep 7;17(9):e1009889. Epub 2021 Sep 7.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis.
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http://dx.doi.org/10.1371/journal.ppat.1009889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448335PMC
September 2021

Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation.

J Psychiatry Neurosci 2021 Sep 1;46(5):E506-E515. Epub 2021 Sep 1.

From the Department of Psychiatry, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China (Duan, Zhu, Yin, R. Zhang, Sun, P. Wang, S. Wang, Tang, F. Wang); the Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, PR China (Duan, Y. Wei, R. Zhang, F. Wang); the Department of Psychiatry and Behavioral Neuroscience, Saint Louis University, St. Louis, MO (Womer); the School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, PR China (X. Zhang); the Department of Radiology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, PR China (Chang, Li, Jiang, S.Wei); the School of Public Health, China Medical University, Shenyang, Liaoning, PR China (Liu); the Department of Psychiatry, College of Medicine, University of Saskatchewan, SK (Y. Zhang).

Background: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter.

Methods: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-β1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function.

Results: In the patient group, abnormal white matter was negatively associated with NRG1-β1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-β1 levels and clinical manifestations.

Limitations: Medication status, the wide age range and our cross-sectional findings were limitations of this study.

Conclusion: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications.
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http://dx.doi.org/10.1503/jpn.200166DOI Listing
September 2021

Fusion Learning for sEMG Recognition of Multiple Upper-Limb Rehabilitation Movements.

Sensors (Basel) 2021 Aug 9;21(16). Epub 2021 Aug 9.

College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.

Surface electromyogram (sEMG) signals have been used in human motion intention recognition, which has significant application prospects in the fields of rehabilitation medicine and cognitive science. However, some valuable dynamic information on upper-limb motions is lost in the process of feature extraction for sEMG signals, and there exists the fact that only a small variety of rehabilitation movements can be distinguished, and the classification accuracy is easily affected. To solve these dilemmas, first, a multiscale time-frequency information fusion representation method (MTFIFR) is proposed to obtain the time-frequency features of multichannel sEMG signals. Then, this paper designs the multiple feature fusion network (MFFN), which aims at strengthening the ability of feature extraction. Finally, a deep belief network (DBN) was introduced as the classification model of the MFFN to boost the generalization performance for more types of upper-limb movements. In the experiments, 12 kinds of upper-limb rehabilitation actions were recognized utilizing four sEMG sensors. The maximum identification accuracy was 86.10% and the average classification accuracy of the proposed MFFN was 73.49%, indicating that the time-frequency representation approach combined with the MFFN is superior to the traditional machine learning and convolutional neural network.
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http://dx.doi.org/10.3390/s21165385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398355PMC
August 2021

ANK3 Gene Polymorphism Rs10994336 Influences Executive Functions by Modulating Methylation in Patients With Bipolar Disorder.

Front Neurosci 2021 4;15:682873. Epub 2021 Aug 4.

Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China.

A large body of evidence suggests that epigenetic modification including DNA methylation plays a critical role in BD's pathogenesis while the identification of methylation quantitative trait loci (meQTLs) shed light on the interpretation of the function of genetic variants in non-coding regions. The intronic single nucleotide polymorphism (SNP) rs10994336 within the ANK3 has emerged as one of the most replicated risk variants for bipolar disorder (BD) in genome-wide association studies. Whether rs10994336 functions as a meQTL to mediate the association between genotype and phenotype remains unclear. A total of 154 patients with BD and 181 healthy controls (HC) were recruited. The genotypes of rs10994336 and methylation levels of CpG sites within ANK3 were tested. Executive functions were assessed using a computerized version of the Wisconsin Card Sorting Test (WCST). Bipolar disorder patients with the risk-T allele of rs10994336 scored lower on tests of executive function compared to homozygous CC carriers, after controlling for age, gender, and education level. No significant difference was found in HC individuals. The risk-T allele is associated with a lower methylation level of CpG site cg02172182 in HC after multiple corrections and replicated in the BD group in the same direction. Further mediation analysis revealed that the cg02172182 methylation significantly mediated the association between the polymorphism rs10994336 and PE index of WCST in patients with BD. Our study suggests that BD-related genetic variant rs10994336 in ANK3 impacts executive functions by modulating ANK3 methylation, supporting the theory that methylation acts as a mediator between genotype and phenotype.
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http://dx.doi.org/10.3389/fnins.2021.682873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371237PMC
August 2021

Does industrial collaborative agglomeration improve environmental efficiency? Insights from China's population structure.

Environ Sci Pollut Res Int 2021 Aug 20. Epub 2021 Aug 20.

School of Public Administration, Dongbei University of Finance & Economics, No. 217 Jianshan Street, Dalian, 116025, Liaoning, China.

Nowadays, the development of green economy and the improvement of environmental efficiency have been a hotspot in both academia and industry. Especially, the effect of the collaborative agglomeration of manufacturing and productive services industries on environmental efficiency has drawn attention from Chinese policymakers, during a critical period of industrial transformation and upgrading and ecological civilization construction in China. However, few studies have explored whether and how industrial collaborative agglomeration affects environmental efficiency based on population structure perspective. To bridge this gap, using the methods of the stochastic frontier approach (SFA), the moderating effect of population structure, and the spatial effect, and employing the panel data of 66 cities in eastern China during 2009-2018, this paper studies the effect of industrial collaborative agglomeration on environmental efficiency and measure the fluctuates of influence including population structure. The results show that industrial collaborative agglomeration has the effect of improving environmental efficiency, and both of them have strong spatial spillover effect. Direct effect of the industrial collaborative agglomeration is more significant positive than indirect effect. It indicates that the environmental efficiency is affected by the industrial collaborative agglomeration in both the local region and neighboring regions. In addition, population density, aging and quality play a positive moderate role by strengthening the spillover effect of industrial collaborative agglomeration, while the moderating effect of population urbanization is not significant. Then, the recommendations and policy implications to improve environmental efficiency are put forward based on the research results: optimizing the coordinated governance system of regional ecological environment, accelerating the innovation of industrial value chain, and promoting the sustainable development of industry and ecology with the advantage of population structure.
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http://dx.doi.org/10.1007/s11356-021-15618-3DOI Listing
August 2021

Cadmium exposure promotes activation of cerebrum and cerebellum ferroptosis and necrosis in swine.

Ecotoxicol Environ Saf 2021 Aug 14;224:112650. Epub 2021 Aug 14.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address:

Cadmium(Cd) is a toxic and carcinogenic heavy metal pollutant leading to serious damage in various organs. Ferroptosis and necrosis as inflammation-related cell death are involved in several diseases of nervous system. In the present study, 10 weaning piglets with similar weight for 6 weeks were randomly divided into two groups. The daily grain containing 0 mg and 20 mg/kg of Cd chloride was fed in 20-26 ℃ environment, animals were sacrificed to collect cerebrum and cerebellum tissues after 40 days. Morphology and ultrastructure results were observed using HE and TEM. Moreover, molecular biological technologies western blot and qRT-PCR were used to detect the expression abundance of genes. Cerebrum and cerebellum injury was observed in Cd-exposed group, antioxidant capacity decreased significantly and oxidative stress increased; immunofluorescence, real-time quantification, and western blot results showed decreased necrosis genes and increased ferroptosis pathway genes abundance in cerebrum, whereas the results were reversed in cerebellum. These results indicated that Cd exposure can activated necrosis and ferroptosis pathways by increased oxidative stress, further resulting in cerebrum and cerebellum damage in pigs. These findings may provide a theoretical basis for early monitoring of Cd exposure in environment.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112650DOI Listing
August 2021

[Regional differences of nucleosides and amino acids in Elaphuri Davidiani Cornu].

Zhongguo Zhong Yao Za Zhi 2021 Jul;46(14):3494-3503

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Key Laboratory of Chinese Medicinal Resources Recycling Utilization under National Administration of Traditional Chinese Medicine,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine Nanjing 210023,China.

In order to reveal the regional characteristics of nucleosides and amino acids in Elaphuri Davidiani Cornu,39 samples of Elaphuri Davidiani Cornu collected from 4 different regions were analyzed by UPLC-QTRAP ~®/MS2 method followed by orthogonal partial least-squares discrimination analysis( OPLS-DA) and cluster analysis( CA). The results showed all the samples contained abundant nucleosides and amino acids,with the total content of 45. 09 μg·g~(-1) and 634. 80 μg·g-1,respectively. The samples presented significant regional differences in the contents of individual components,and the main differential components included Ura,Hpro,Thr,Glu,G5 P,2'-dG,Adeno,Met,Ade,Gln,Orni,Phe,2'-dA,Hit,Lys,and Ile. Among them,Ura,Met,Glu,and Ile had the highest content in the samples from Dafeng in Jiangsu,Qinhu in Jiangsu,Beijing,and Shishou in Hubei,respectively. OPLS-DA and CA demonstrated that all the samples of Elaphuri Davidiani Cornu could be divided into three categories,reflecting the regional characteristics. The results indicated that the accumulation of nucleosides and amino acids in Elaphuri Davidiani Cornu was closely related to its habitat,providing a useful reference for the research on the quality formation,quality evaluation and control,as well as the comprehensive utilization of Elaphuri Davidiani Cornu. The findings suggested that the content factors of Ura,Met,Glu,and Ile could be included into the quality standard system of Elaphuri Davidiani Cornu as the characteristics of medicinal materials from different regions.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210310.304DOI Listing
July 2021

[Textual and information research of classical prescription Mijiao Pills].

Zhongguo Zhong Yao Za Zhi 2021 Jul;46(14):3478-3486

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine , Key Laboratory of Chinese Medicinal Resources Recycling Utilization,National Administration of Traditional Chinese Medicine/Jiangsu Key Laboratory for High Technology Research of TCM Formulae,School of Pharmacy,Nanjing University of Chinese Medicine Nanjing 210023,China.

Elaphurus davidianus( Milu),a rare animal unique to China,has been used as medicine for more than a thousand years,but the extinction of Milu in modern times resulted in the unavailability of related medical products. Today,the reintroduction of Milu population makes it possible to restore its medicinal usage. The resource reserves of Cervi Cornu,the natural shedding product from Milu,are increasing with the expansion of the population,allowing it to be fully utilized in the medical field. Mijiao Pills,first recorded in Important Prescriptions Worth a Thousand Gold for Emergency( Bei Ji Qian Jin Yao Fang) by Sun Simiao in the Tang Dynasty,is the first Chinese medicinal prescription with Cervi Cornu as the sovereign medicinal,which is effective in tonifying. Its composition,preparation,efficacy and indications,and administration are described in detail in the Important Prescriptions Worth a Thousand Gold for Emergency,which however,have changed significantly over the thousands of years,seriously affecting the clinical application of this classical prescription and related product development. Therefore,the key information of this prescription should be systematically collated and summarized. According to the principles of textual research on key information in ancient classical prescriptions promulgated by relevant authorities,this paper reviewed ancient Chinese medical books of the past dynasties,modern literature,as well as the Pharmacopoeia of the People's Republic of China( 2020 Version) to figure out such key information as the source,historical evolution,original plants and animals and their processing,dosage,preparation,and usage of Mijiao Pills. This paper aimed to provide a basis for the clinical application of Mijiao Pills and subsequent product development,thus facilitating the development and utilization of this precious medicinal animal resource.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210501.101DOI Listing
July 2021

Myofascial Release for Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

Front Med (Lausanne) 2021 28;8:697986. Epub 2021 Jul 28.

Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, China.

Chronic low back pain (CLBP) is one of the most common musculoskeletal diseases in the elderly, which has a severe impact on the health of the elderly. However, CLBP treatment is very challenging, and more effective treatment methods are needed. Myofascial release may be an effective therapy for the management of chronic musculoskeletal pain. It is widely used clinically to treat CLBP, but its clinical efficacy is still controversial. This study aims to systematically evaluate the effectiveness of myofascial release for patients with CLBP. We selected PubMed, Cochrane Library, EMBASE database, and Web of Science database articles published until April 5, 2021. Randomized controlled trials (RCTs) of myofascial release for CLBP were included. Outcome measures included pain, physical function, quality of life, balance function, pain pressure-threshold, trunk mobility, and mental health. For each outcome, Standardized mean differences (SMD) or mean differences (MD) and 95% confidence intervals (CIs) were calculated. Eight RCTs ( = 375) were included based on inclusion and exclusion criteria. The meta-analysis showed that the overall efficacy of myofascial release for CLBP was significant, including two aspects: pain [SMD = -0.37, 95% CI (-0.67, -0.08), = 46%, = 0.01] and physical function [SMD = -0.43, 95% CI (-0.75, -0.12), = 44%, = 0.007]. However, myofascial release did not significantly improve quality of life [SMD = 0.13, 95% CI (-0.38, 0.64), = 53%, = 0.62], balance function [SMD = 0.58, 95% CI (-0.49, 1.64), = 82%, = 0.29], pain pressure-threshold [SMD = 0.03,95% CI (-0.75, 0.69), = 73%, = 0.93], trunk mobility [SMD = 1.02, 95% CI (-0.09, 2.13), = 92%, = 0.07] and mental health [SMD = -0.06, 95% CI (-0.83, 0.71), = 73%, = 0.88]. In this study, we systematically reviewed and quantified the efficacy of myofascial release in treating CLBP. The meta-analysis results showed that myofascial release significantly improved pain and physical function in patients with CLBP but had no significant effects on balance function, pain pressure-threshold, trunk mobility, mental health, and quality of life. However, due to the low quality and a small number of included literature, more and more rigorously designed RCTs should be included in the future to verify these conclusions.
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http://dx.doi.org/10.3389/fmed.2021.697986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355621PMC
July 2021

[Effectiveness of robot assisted percutaneous kyphoplasty for treatment of single/double-segment osteoporotic vertebral compression fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Aug;35(8):1000-1006

Department of Orthopedics, the First Hospital of China Medical University, Shenyang Liaoning, 110001, P.R.China.

Objective: To compare the effectiveness of robot assisted and C-arm assisted percutaneous kyphoplasty (PKP) in the treatment of single/double-segment osteoporotic vertebral compression fracture (OVCF).

Methods: The clinical data of 108 cases of single/double-segment OVCF who met the selection criteria between May 2018 and October 2019 were retrospectively analyzed. There were 65 cases of single-segment fractures, of which 38 cases underwent "TiRobot" orthopedic robot-assisted PKP (robot group), 27 cases underwent C-arm X-ray machine fluoroscopy-assisted PKP (C-arm group). There were 43 cases of double-segment fractures, including 21 cases in robot group and 22 cases in C-arm group. There was no significant difference in gender, age, T value of bone mineral density, fracture segment distribution, time from injury to operation, and preoperative visual analogue scale (VAS) score, vertebral kyphosis angle (VKA), and height of fractured vertebra (HFV) in the patients with single/double-segments fractures between robot group and C-arm group ( >0.05). The operation time, the fluoroscopy frequency of the surgeons and the patient, the fluoroscopy exposure time of the surgeons and the patient, the radiation dose of the C-arm; the VAS scores, VKA, HFV before operation, at 1 day and 6 months after operation; and the complications in the two groups were recorded and compared.

Results: All patients underwent surgery successfully. The operation time of the single-segment robot group was significantly longer than that of the C-arm group ( =5.514, =0.000), while the operation time of the double-segment robot group was not significantly different from that of the C-arm group ( =1.892, =0.205). The single/double-segment robot group required three-dimensional scanning, so the fluoroscopy frequency, fluoroscopy exposure time, and radiation dose of C-arm received by the patient were significantly higher than those of the C-arm group ( <0.05); the fluoroscopy frequency and the fluoroscopy exposure time received by the surgeons were significantly less than those of the C-arm group ( <0.05). There was no infection, embolism, neurological injury, and adjacent segmental fractures. The single/double-segment robot group showed lower rate of cement leakage when compared with the C-arm group ( <0.05), all the cases of cement leakage happened outside the spinal canal. The VAS score, VKA, and HFV of the single/double-segment robot group and the C-arm group were significantly improved at 1 day and 6 months after operation ( <0.05), and the VAS score at 6 months after operation was further improved compared with that at 1 day after operation ( <0.05). At 1 day and 6 months after operation, there was no significant difference in VAS score between the single/double-segment robot group and the C-arm group ( >0.05). The VKA and HFV of robot group were significantly better than those of the C-arm group ( <0.05).

Conclusion: For single/double-segment OVCF, robot assisted PKP has more advantages in correcting VKA and HFV, reducing fluoroscopy exposure of surgeons and bone cement leakage rate; C-arm assisted PKP has more advantages in reducing the operation time of single-segment OVCF and fluoroscopy exposure of patients during operation.
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http://dx.doi.org/10.7507/1002-1892.202103151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404010PMC
August 2021

Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma.

Front Cell Dev Biol 2021 27;9:688070. Epub 2021 Jul 27.

Department of Gastroenterology, The Affiliated Jiangyin Hospital of Xuzhou Medical University, Jiangyin, China.

Objective: The emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect.

Methods: The degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the [email protected]@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect and the bio-safety of PMPNs.

Results: The prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety.

Conclusion: In this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.
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http://dx.doi.org/10.3389/fcell.2021.688070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353447PMC
July 2021

PKCι regulates the expression of PDL1 through multiple pathways to modulate immune suppression of pancreatic cancer cells.

Cell Signal 2021 Oct 8;86:110115. Epub 2021 Aug 8.

Department of Immunology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 3-17 Renmin South Road, Chengdu, Sichuan 610041, PR China. Electronic address:

To investigate the impact of oncogenic protein kinase C isoform ι (PKCι) on the microenvironment and the immunogenic properties of pancreatic tumors, we prohibit PKCι activity in various pancreatic ductal adenocarcinoma (PDAC) cell lines and co-culture them with human natural killer NK92 cells. The results demonstrate that PKCι suppression enhances the susceptibility of PDAC to NK cytotoxicity and promotes the degranulation and cytolytic activity of co-cultured NK92 cells. Mechanistic studies pinpoint that downstream of KRAS, both YAP1 and STAT3 are recruited by oncogenic PKCι to elevate the expression of PDL1, contributing to constitute an immune suppressive microenvironment in PDAC. Co-culture with NK92 further induces PDL1 upregulation via STAT3 to stimulate immune escape of PDAC cells. Subsequently, inhibition of PKCι in PDAC alleviates the immune suppression and enhances the cytotoxicity of NK92 towards PDAC through restraining PDL1 overexpression. Combined with PD1/PDL1 blocker, PKCι inhibitor remarkably elevates the cytotoxicity of NK92 against PDAC cells in vitro, establishing PKCι inhibitor as a promising candidate for boosting the immunotherapy of PDAC.
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http://dx.doi.org/10.1016/j.cellsig.2021.110115DOI Listing
October 2021

The effect of felt trust from patients among nurses on attitudes towards nursing service delivery.

J Adv Nurs 2021 Aug 7. Epub 2021 Aug 7.

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Aims: To examine how felt trust motivates nurses to desire to deliver better nursing services and how perspective taking makes nurses feel trusted by their patients. By introducing the concept of prosocial motivation into nursing research, this study further explored a boundary condition that influences the positive relationship between felt trust from patients and attitudes towards nursing service delivery.

Design: This study used a cross-sectional and survey design.

Method: This study was conducted among 339 nurses on medical teams sent to support Hubei, China, during the COVID-19 pandemic in April 2020.

Results: The results indicate that felt trust from patients mediated the positive relationship between perspective taking and attitudes towards nursing service delivery. In addition, prosocial motivation moderated the relationship between felt trust from patients and attitudes towards nursing service delivery, such that the relationship was stronger when prosocial motivation was high (vs. low). Prosocial motivation also moderated the indirect effects of perspective taking on attitudes towards nursing service delivery via felt trust from patients.

Conclusion: This study shows that despite the challenges posed by COVID-19, nurses who experience a high level of trust from patients are still eager to deliver high-quality nursing services, and this finding is especially salient among those with high prosocial motivation.

Impact: This study introduces felt trust from patients as a new motivational mechanism that can induce nurses' willingness to deliver better nursing services. We suggest that nurses and nurse leaders should be aware of the significance of the trust relationship between nurses and patients. Nurses need to be trained to take patients' perspectives in the interaction process, which can make them feel trusted by patients and can consequently be motivated to deliver better nursing services.
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http://dx.doi.org/10.1111/jan.14973DOI Listing
August 2021

Cadmium exposure triggers oxidative stress, necroptosis, Th1/Th2 imbalance and promotes inflammation through the TNF-α/NF-κB pathway in swine small intestine.

J Hazard Mater 2021 Jul 20;421:126704. Epub 2021 Jul 20.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P. R. China. Electronic address:

Cadmium (Cd) is a toxic environmental pollutant and induces toxic effects to organism. Nevertheless, the mechanism of Cd-induced toxicity in swine remains obscure. To explore this, 10 healthy 6-week-old weaned swine were placed into two groups stochastically, the Cd group was treated with a commercial diet containing 20 mg/kg Cd for 40 days. The results of histopathological and ultrastructural observations showed typical necrosis features and inflammatory cell infiltration in Cd group. Excessive Cd suppressed T-AOC and SOD activities, increased MDA content and ROS levels. Cd diet elevated the expression of RIPK1, RIPK3, and MLKL to activate the RIPK3-dependent necroptosis pathway. Results of Th1 and Th2 cytokines indicated that the levels of IL-4, IL-6 and IL10 was increased, while the level of IFN-γ was decreased, illustrating Th1/Th2 immune imbalance leads to aggravate inflammatory responses. Cd activated the TNF-α/NF-κB pathway and induced inflammatory responses via increasing the expression of HO-1, IL-1β, iNOS, COX2. Heat shock proteins were notably elevated in response to inflammatory reactions. And these effects were inhibited by necrostatin-1 (Nec-1) and N-acetyl-cysteine (NAC). Altogether, these data demonstrated that Cd induced necroptosis and inflammation to aggravate small intestine injury in swine by increasing the excessive accumulation of ROS and imbalanced Th1/Th2, respectively.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126704DOI Listing
July 2021

Hybrid-pair ratio adjustable power splitters for add-on RF shimming and array-compressed parallel transmission.

Magn Reson Med 2021 Jul 19. Epub 2021 Jul 19.

Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, USA.

Purpose: A ratio adjustable power splitter (RAPS) circuit was recently proposed for add-on RF shimming and array-compressed parallel transmission. Here we propose a new RAPS circuit design based on off-the-shelf components for improved performance and manufacturability.

Theory And Methods: The original RAPS used a pair of home-built Wilkinson splitter and hybrid coupler connected by a pair of connectorized coaxial cables. Here we propose a new hybrid-pair RAPS (or HP-RAPS) circuit that replaces the home-built circuits with two commercially available hybrid couplers and replaces connectorized cables with interchangeable microstrip lines. We derive the relation between the desired splitting ratio and the required phase shifts for HP-RAPS and investigate how to generate arbitrary splitting ratios using paired meandering and straight lines. Several HP-RAPSs with different splitting ratios were fabricated and tested on the workbench and MRI experiments.

Results: The splitting ratio of an HP-RAPS circuit has a tan or cot dependence on the meandering line's additional length compared to the straight line. The fabricated HP-RAPSs exhibit accurate splitting ratios as expected (<4% deviations) and generate transmit fields that well agree with predicted fields. They also demonstrated a low insertion loss of 0.33 dB, high output isolation of -26 dB, and acceptable impedance matching of -16 dB.

Conclusion: A novel HP-RAPS circuit was developed and implemented. It is easy-to-fabricate/reproduce with minimal expertise. It also preserves the features of the original RAPS circuit (ratio-adjustable, small footprint, etc.) with lower insertion loss.
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http://dx.doi.org/10.1002/mrm.28934DOI Listing
July 2021

β-Catenin/LEF-1 transcription complex is responsible for the transcriptional activation of LINC01278.

Cancer Cell Int 2021 Jul 17;21(1):380. Epub 2021 Jul 17.

Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, No. 107 of Yanjiangxi Road, Guangzhou, 510120, Guangdong, People's Republic of China.

Background: Our previous study shows that LINC01278 inhibits the malignant proliferation and invasion of papillary thyroid carcinoma (PTC) cells by regulating the miR-376c-3p/DNM3 axis. However, the regulation mechanism of LINC01278 expression in PTC cells is still unclear.

Methods: The luciferase reporter and ChIP assays were used to confirm the binding of LEF-1 to the putative promoter site of LINC01278 gene. The RNA immunoprecipitation and RNA pulldown were used to determine the enrichment of LINC01278 in β-catenin protein. The proteasome inhibitors (MG132) was used for detecting the β-catenin ubiquitination-proteasome degradation. Wnt/β-catenin specific agonists (LiCI), inhibitors (WiKI4) and TOP/FOP-flash reporter assay were used for detecting the activation of Wnt/β-catenin signal. Western blot was used to detected the expression of target proteins.

Results: The online PROMO algorithm determines a putative LEF-1 binding site on LINC01278 promoter, the LEF-1 binds to the putative promoter site of LINC01278 gene, and β-catenin enhances the binding of LEF-1 to the LINC01278 gene promoter. Furthermore, LINC01278 negatively regulated the protein accumulation of β-catenin in the cytoplasm, into nucleus, and ultimately inhibited the transcription of downstream target genes activated by Wnt/β-catenin signal. The results of RNA immunoprecipitation and RNA pulldown proved the direct binding of LINC01278 to β-catenin protein. In addition, the combination of LINC01278 and β-catenin promotes the β-catenin ubiquitination-proteasome degradation.

Conclusion: In summary, we found the transcriptional activation of LINC01278 by the β-catenin/LEF-1 transcription factor, and the negative feedback regulation of LINC01278 onβ-catenin signal.
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http://dx.doi.org/10.1186/s12935-021-02082-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285859PMC
July 2021

Bacterial spectrum analysis and antimicrobial susceptibility study of osteoradionecrosis of the jaw in Southern China.

Oral Dis 2021 Jul 17. Epub 2021 Jul 17.

Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.

Objective: Osteoradionecrosis of the jaw (ORNJ) is one of the most common and serious complications after radiotherapy of head and neck malignancies due to the high incidence of nasopharyngeal cancer in Southern China. Clinicians lack understanding and consensus on anti-infective treatment in ORNJ lesions. This research aims to provide evidence for rational use of antibiotics by reviewing the bacterial spectrums and antimicrobial susceptibility test of ORNJ patients.

Methods: We collected patient who was diagnosed with ORNJ from November 2012 to June 2019 in our hospital. Exudate or bone unexposed wound surface sampling, agar plates culturing, and susceptibility testing were analyzed. Descriptive statistics were used for data presentation.

Results: A total of 219 samples were collected in our retrospective study. The most common cultured bacteria were Klebsiella pneumoniae (15.10%), Pseudomonas aeruginosa (13.54%), and Staphylococcus aureus (10.94%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 5.21% in the whole positive samples. Ticarcillin, Ofloxacin, Vancomycin, Tigecycline, and Meropenem were more susceptible than other antibiotics to treat uncontrollable infection.

Conclusions: Our research provided objective evidence for understanding the types of local bacterial flora and drug susceptibility in ORNJ lesions and gave a guiding reference for empirical antibiotics medication.
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http://dx.doi.org/10.1111/odi.13968DOI Listing
July 2021

Individualized resuscitation strategy for septic shock formalized by finite mixture modeling and dynamic treatment regimen.

Crit Care 2021 07 12;25(1):243. Epub 2021 Jul 12.

Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People's Republic of China.

Background: Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class.

Methods: Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset.

Results: A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion.

Conclusions: Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.
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http://dx.doi.org/10.1186/s13054-021-03682-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273991PMC
July 2021

Early onset atrial lesions in a patient with a novel LMNA frameshift mutation.

Hum Mol Genet 2021 Jul 8. Epub 2021 Jul 8.

Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Genetic mutations in the lamin A/C gene (LMNA) have been linked to cardiomyopathy. Different mutational sites exhibit different clinical manifestations and prognoses. Herein, we identified a novel LMNA frameshift mutation, p.P485Tfs*67, from a patient with early-onset atrial disease. To verify the pathogenicity of this variation, a transgenic zebrafish model was constructed, which demonstrated that adult zebrafish with the LMNA mutation showed an abnormal ECG and impaired myocardial structure. Our study suggests the atrial pathogenicity of the LMNA-P485Tfs mutation, which is helpful to understand the function of the Ig-like domain of lamin A/C.
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http://dx.doi.org/10.1093/hmg/ddab186DOI Listing
July 2021

Mill. var. (Bunge) Hu ex H. F. Chou Seed Ameliorates Insomnia in Rats by Regulating Metabolomics and Intestinal Flora Composition.

Front Pharmacol 2021 16;12:653767. Epub 2021 Jun 16.

State Administration of Traditional Chinese Medicine Key Laboratory of Chinese Medicinal Resources Recycling Utilization, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

The seed of Mill. var. (Bunge) Hu ex H. F. Chou (ZSS) is often used as a traditional Chinese medicine for insomnia due to its sedative and hypnotic effects, but the mechanism underlying this effect has not been thoroughly elucidated. In this study, an insomnia model induced by intraperitoneal injection of DL-4-chlorophenylalanine suspension in Sprague-Dawley rats was adopted to investigate the therapeutic effect of ZSS extract. Metabolomics analyses of plasma and urine as well as 16S rRNA gene sequencing of the intestinal flora were performed. The relationships between the plasma and urine metabolites and the intestinal flora in insomnia rats were also analyzed. The results showed that changes in plasma and urine metabolites caused by insomnia were reversed after administration of ZSS, and these changes were mainly related to amino acid metabolism, especially phenylalanine metabolism. The results of 16S rRNA gene sequencing and short-chain fatty acid determination showed that the ZSS extract could reverse the imbalance of intestinal flora caused by insomnia and increase the contents of SCFAs in feces. All of these improvements are mainly related to the regulation of inflammation. Therefore, it is concluded that insomnia, which alters metabolic profiles and the intestinal flora, could be alleviated effectively by ZSS extract.
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http://dx.doi.org/10.3389/fphar.2021.653767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241942PMC
June 2021

A complete chloroplast genome of (Pinaceae) and its phylogenetic implications.

Mitochondrial DNA B Resour 2021 Jun 21;6(7):2074-2075. Epub 2021 Jun 21.

Co-Innovation Center for Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Nanjing, PR China.

(Bertrand) Beissner 1891 (Pinaceae) is a rare tertiary relict plant endemic to China. However, since the main morphological characteristics used for identifying are variable, some taxonomic treatments within the species are still controversial. Here a complete chloroplast genome of representing a special genotype was assembled, which could provide more information for the taxonomic study of this species. The assembled genome was 117,642 bp in length with a large single-copy (LSC) region (74,825 bp), a small single-copy (SSC) region (40,247 bp), and two incomplete inverted repeats (IRs) regions (1285 bp each). In total, 118 genes were predicted, including 4 s, 34 s, and 80 protein-coding genes. The overall GC content of the assembled genome was 38.5%. Phylogenetic analysis showed that different accessions of formed a clade with relatively low support (bootstrap value = 71), which indicated a high level of sequences variation within the species.
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http://dx.doi.org/10.1080/23802359.2021.1907253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218866PMC
June 2021

CaCO-Chitosan Composites Granules for Instant Hemostasis and Wound Healing.

Materials (Basel) 2021 Jun 17;14(12). Epub 2021 Jun 17.

Department of Spine Surgery, Beijing JiShuiTan Hospital, 4th Medical College of Peking University, Xicheng District, Xinjiekou No. 31 East Street, Beijing 100035, China.

Excessive bleeding induces a high risk of death and is a leading cause of deaths that result from traffic accidents and military conflict. In this paper, we developed a novel porous chitosan-CaCO (CS-CaCO) composite material and investigated its hemostatic properties and wound healing performance. The CS-CaCO composites material was prepared via a wet-granulation method. Granulation increases the infiltrating ability of the CS-CaCO composites material. The improved water absorption ability was enhanced to 460% for the CS-CaCO composites material compared to the CaCO or chitosan with only one single component. The coagulation studies in vivo illustrated that the blood clotting time was greatly reduced from 31 s for CaCO to 16 s for the CS-CaCO composite material. According to the results of the wound healing experiments in rats, it was found that the CS-CaCO3 composite material can promote wound healing. The CS-CaCO composite material could accelerate wound healing to a rate of 9 days, compared with 12 days for the CaCO. The hemostatic activity, biocompatibility, and low cost of CS-CaCO composite material make it a potential agent for effective hemostatic and wound healing materials.
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http://dx.doi.org/10.3390/ma14123350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234285PMC
June 2021

Psychotropic Polypharmacy in the US Pediatric Population: A Methodologic Critique and Commentary.

Front Psychiatry 2021 14;12:644741. Epub 2021 Jun 14.

Department of Psychiatry, The Johns Hopkins Hospital, Johns Hopkins Medicine, Baltimore, MD, United States.

Psychotropic concomitant medication use for the treatment of youth with emotional and behavioral disorders has grown significantly in the U.S. over the past 25 years. The use of pharmacy claims to analyze these trends requires the following: age of the selected population, overlapping days of use, and precision of the outcome itself. This review will also address the gaps in reporting of pediatric psychotropic polypharmacy. An electronic literature search was undertaken for the period 2000 through 2020 using keywords such as "pediatric," "concomitant," "polypharmacy," "multiple medications," and "concurrent psychotropic"; Relevant references in textbooks were also used. Only English language and U.S. studies were included, resulting in 35 inter-class studies. Studies were organized into seven groups according to data sources and clinical topics: (1) population surveys; (2a) multi-state publicly insured populations; (2b) single/two state studies; (3) privately insured populations; (4) diagnosed populations; (5) foster care populations; (6) special settings. Across 20 years it is apparent that pediatric psychotropic polypharmacy affects substantially more children and adolescents today than had been the case. As many as 300,000 youth now receive 3 or more classes concomitantly. The duration of concomitant use is relatively long, e.g., 69-89% of annual medicated days. Finally, more adverse event reports were associated with 3-class compared with 2-class drug regimens. Factors that contribute to the growth of pediatric psychotropic polypharmacy include: (1) predominance of the biological model in psychiatric practice; (2) invalid assumptions on efficacy of combinations, (3) limited professional awareness of metabolic and neurological adverse drug events, and (4) infrequent use of appropriate deprescribing. A review of publications documenting U.S. pediatric psychotropic polypharmacy written over the last 20 years supports the need to standardize the methodologies used. The design of population-based studies should maximize information on the number of youth receiving regimens of 3-, 4-, and 5 or more concomitant classes and the duration of such use. Next, far more post-marketing research is needed to address the effectiveness, safety and tolerability of complex drug regimens prescribed for youngsters.
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http://dx.doi.org/10.3389/fpsyt.2021.644741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236612PMC
June 2021

Metal-organic framework-based micropipette is a metal ion responsive nanochannel after adsorbing HS.

Chem Commun (Camb) 2021 Jul;57(58):7152-7155

College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325000, P. R. China.

Glass micropipettes are easy to fabricate, have excellent flexibility and stable properties. HKUST-1 and MIL-68(In) are in situ grown in the tip of a micropipette to construct porous nanochannels. After absorbing H2S, the MIL-68(In)-based nanochannel shows effective metal ion responsiveness for Hg2+-detection.
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http://dx.doi.org/10.1039/d1cc02411fDOI Listing
July 2021

Prognostic and Predictive Value of Immune-Related Gene Pair Signature in Primary Lower-Grade Glioma Patients.

Front Oncol 2021 27;11:665870. Epub 2021 May 27.

Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Immune-related gene pairs (IRGPs) have been associated with prognosis in various cancer types, but few studies have examined their prognostic capabilities in glioma patients. Here, we gathered the gene expression and clinical profile data of primary lower-grade glioma (LGG) patients from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA, containing CGGAseq1 and CGGAseq2), the Gene Expression Omnibus (GEO: GSE16011), and Rembrandt datasets. In the TCGA dataset, univariate Cox regression was performed to detect overall survival (OS)-related IRGs, Lasso regression, and multivariate Cox regression were used to screen robust prognosis-related IRGs, and 19 IRGs were selected for the construction of an IRGP prognostic signature. All patients were allotted to high- and low-risk subgroups based on the TCGA dataset median value risk score. Validation analysis indicated that the IRGP signature returned a stable prognostic value among all datasets. Univariate and multivariate Cox regression analyses indicated that the IRG -signature could efficiently predict the prognosis of primary LGG patients. The IRGP-signature-based nomogram model was built, revealing the reliable ability of the IRGP signature to predict clinical prognosis. The single-sample gene set enrichment analysis (ssGSEA) suggested that high-risk samples contained higher numbers of immune cells but featured lower tumor purity than low-risk samples. Finally, we verified the prognostic ability of the IRGP signature using experiments performed in LGG cells. These results indicated that the IRGP signature could be regarded as a stable prognostic assessment predictor for identifying high-risk primary LGG patients.
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http://dx.doi.org/10.3389/fonc.2021.665870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190397PMC
May 2021

White matter tracts in Bipolar Disorder patients: A comparative study based on diffusion kurtosis and tensor imaging.

J Affect Disord 2021 09 27;292:45-55. Epub 2021 May 27.

Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.. Electronic address:

Background: Diffusion kurtosis imaging (DKI), an extension of diffusion tensor imaging (DTI), is a powerful tool for studying human brain.The purpose is to investigate differences between DKI and DTI by comparing parameters in same analysis methods with bipolar disorder (BD) patients.

Methods: In this study, we attained in 47 BD patients and 49 age-, sex-, and education-matched healthy controls, complimented DTI and DKI scanning and got Fractional Anisotropy (FA), Mean Diffusion (MD) and Mean Kurtosis (MK). Voxel-wise statistical analysis was performed by the tract-based spatial statistics (TBSS) analysis and atlas-based regional data analysis.

Results: TBSS analysis showed more widespread regions and higher fidelity in DKI parameters than DTI parameters with the same p-value threshold, and DKI parameters showed significant alterations after Family-Wise Error correction. The DKI-FA value in the corpus callosum, bilateral cingulum (cingulate gyrus), bilateral superior corona radiata, left anterior corona radiata and left posterior corona radiata of BD patients was negatively correlated with the duration of illness. In the atlas-based regional data analysis, the effect size of DTI-FA, DTI-MD, DKI-FA and DKI-MD were quantified using Cohen's d value. DKI-FA and DKI-MD demonstrated more between-group different regions and the higher (p < 0.001) absolute Cohen's d value than DTI-FA.

Limitations: This study did not consider the difference between sub-types of BD.

Conclusions: Compared to DTI parameters, DKI parameters were more sensitive and stable to probe the local microstructure, and particularly powerful to exploit cerebral alterations in BD patients.
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http://dx.doi.org/10.1016/j.jad.2021.05.030DOI Listing
September 2021
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