Publications by authors named "Jun Wang"

8,480 Publications

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Cytogenetic Analysis of the Products of Conception After Spontaneous Abortion in the First Trimester.

Cytogenet Genome Res 2021 May 11:1-12. Epub 2021 May 11.

Department of Gynecologic Oncology, Central Clinical College of Gynecology and Obstetrics, Tianjin Medical University, Tianjin, China.

In the present study, we retrospectively recruited 340 patients who underwent spontaneous abortions to investigate chromosomal abnormalities of the conception products in the first trimester. We also performed a relevant analysis of clinical factors. Of these patients, 165 had conception products with chromosomal abnormalities, including 135 aneuploidies, 11 triploidies, 10 complex abnormalities, and 9 segmental aneuploidies. The most common abnormal chromosomes were chromosome 16 in the embryo-transfer group and sex chromosomes in the natural-conception group. The most common abnormal chromosomes in all analyzed maternal age groups were sex chromosomes, 16, and 22. The chromosomal abnormality incidence was related to age and number of spontaneous abortions (both p < 0.05), but not to number of pregnancies, deliveries, induced abortions, or methods of conception (all p > 0.05). The rates of abnormality for chromosomes 12, 15, 20, and 22 increased with age, while the rates for chromosomes 6, 7, 13, and X decreased. In all age groups, aneuploidy was by far the most common abnormality; however, the low-incidence distributions of chromosomal abnormalities were entirely different. Overall, chromosomal aneuploidy was the primary cause of pregnancy loss in the first trimester, and low-frequency abnormalities differed across age subgroups. Chromosomal aberrations were found to be related to maternal age and spontaneous abortion, but not all chromosomal abnormalities increased with age.
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http://dx.doi.org/10.1159/000514088DOI Listing
May 2021

Determining the effects of blended learning using the community of inquiry on nursing students' learning gains in sudden patient deterioration module.

Nurs Open 2021 May 11. Epub 2021 May 11.

Department of Nursing, Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Aims: To determine the effectiveness of blended learning using the community of inquiry framework on nursing students' learning gains in a sudden patient deterioration module.

Design: A quasi-experimental trial.

Methods: 233 Chinese nursing students in their fourth semester of a sudden patient deterioration learning module were assigned to control (N = 113) and experimental group (N = 120). Students in experimental group engaged in community of inquiry-based blended learning in sudden patient deterioration module, including computer-aided self-instruction, team-based topic discussion and simulation training. Control group learned similar contents through face-to-face teaching comprising of a presentation with lecture, tutorial and simulation training. Student assessment of learning gains, knowledge and practical ability was quantified after the interventions.

Results: Compared with control group, students in experimental group had improved student assessment of learning gains (p = .001, Cohen d = 0.69) and practical ability (p < .001, Cohen d = 0.48). Although no significant difference in overall knowledge score, experimental group students did better performance in application and analysis (p = .001, Cohen d = 0.45).
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http://dx.doi.org/10.1002/nop2.914DOI Listing
May 2021

Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week.

Nat Commun 2021 May 10;12(1):2581. Epub 2021 May 10.

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China.

While the potential of patient-derived organoids (PDOs) to predict patients' responses to anti-cancer treatments has been well recognized, the lengthy time and the low efficiency in establishing PDOs hamper the implementation of PDO-based drug sensitivity tests in clinics. We first adapt a mechanical sample processing method to generate lung cancer organoids (LCOs) from surgically resected and biopsy tumor tissues. The LCOs recapitulate the histological and genetic features of the parental tumors and have the potential to expand indefinitely. By employing an integrated superhydrophobic microwell array chip (InSMAR-chip), we demonstrate hundreds of LCOs, a number that can be generated from most of the samples at passage 0, are sufficient to produce clinically meaningful drug responses within a week. The results prove our one-week drug tests are in good agreement with patient-derived xenografts, genetic mutations of tumors, and clinical outcomes. The LCO model coupled with the microwell device provides a technically feasible means for predicting patient-specific drug responses in clinical settings.
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http://dx.doi.org/10.1038/s41467-021-22676-1DOI Listing
May 2021

Detection of CTX-M-27 β-lactamase genes on two distinct plasmid types in ST38 from three US states.

Antimicrob Agents Chemother 2021 May 10. Epub 2021 May 10.

University of Rochester Medical Center, Clinical Microbiology, Department of Pathology and Laboratory Medicine, Rochester, NY

Infections caused by extended-spectrum β-lactamase (ESBL)-producing are a significant cause of morbidity and healthcare costs. Globally, the prevailing clonal type is ST131 in association with the blaCTX-M-15 β-lactamase gene. However, other ESBLs such as blaCTX-M-14 and blaCTX-M-27 can also be prevalent in some regions. We identified ST38 ESBL-producing from different regions in the US which carry blaCTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.
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http://dx.doi.org/10.1128/AAC.00825-21DOI Listing
May 2021

Ultra-high mechanical property and multi-layer porous structure of amidoximation ethylene-acrylic acid copolymer balls for efficient and selective uranium adsorption from radioactive wastewater.

Chemosphere 2021 Apr 30;280:130722. Epub 2021 Apr 30.

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China; Institute of Advanced Marine Materials, Harbin Engineering University, 150001, China. Electronic address:

Adsorption uranium [U(VI)] from U-containing radioactive wastewater (URW) is a critical strategy for solving the resource shortage and environmental pollution in pace with the sustainable development of nuclear energy. However, the URW universally exhibits acidity and contains co-existing metal ions with high concentration. Herein, the amidoximation ethylene-acrylic acid copolymer balls (EAA-AO) with aciduric and super-high mechanical property were successfully synthesized through grafting diaminomaleonitrile and further treatment of amidoximation. Significantly, the mechanical properties of EAA-AO were not affected by the grafting process and maintained super-high mechanical properties. Furthermore, the -NH and unreacted -CN groups in diaminomaleonitrile adjusted the pK to make the optimal pH be 4. In addition, the microstructure of EAA-AO was transformed from the original dense to multi-layer porous structure, which promoted the mass transfer process and the contact between uranyl ions (UO) and internal adsorption active sites. The adsorption capacity of EAA-AO was about 1.78 times that of EAA at pH = 4, and the adsorption capacity for U(VI) was about 8.17 times that of Ba with the second highest adsorption capacity. Therefore, the EAA-AO exhibited ultra-high adsorption performance (q = 3.196 mg g) in the artificial radioactive wastewater, laying a good foundation for subsequent large-scale industrial adsorption of U(VI) in nuclear industrial wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130722DOI Listing
April 2021

Deciphering the Formulation Secret Underlying Chinese Huo-Clearing Herbal Drink.

Front Pharmacol 2021 22;12:654699. Epub 2021 Apr 22.

Laboratory of Drug Discovery and Molecular Engineering, Department of Medicinal Plants, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, China.

Herbal teas or herbal drinks are traditional beverages that are prevalent in many cultures around the world. In Traditional Chinese Medicine, an herbal drink infused with different types of medicinal plants is believed to reduce the 'Shang Huo', or excessive body heat, a status of sub-optimal health. Although it is widely accepted and has a very large market, the underlying science for herbal drinks remains elusive. By studying a group of herbs for drinks, including 'Gan' ( Fisch. Ex DC.), 'Ju' ( (Ramat.) Tzvelev), 'Bu' ( L.), 'Jin' ( Thunb.), 'Xia' ( L.), and 'Ji' ( L.), the long-term jargon is connected with the inflammation of modern immunology through a few pro-inflammatory markers. studies have indicated that cellular inflammation is lowered by Ju and Jin either individually or synergistically with Gan. Among all herbs, only Gan detoxicated cellular toxicity of Bu in a dose dependent manner. The synergistic formulation of Ju and Gan, or Jin and Gan, in a reduction of Shang Huo, was tested . Both combinations exhibited a lower percentage of neutrophils, monocytes, and CD4/CD8 ratio in the blood, as well as inflammatory cytokines. Furthermore, body weight in the combinatory groups was more stable than treatments using single herbs. The combination of old traditional oriental methods with Western science logistics, has resulted in the formulation of different herbs into one concoction for the use of detoxification and synergism.
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http://dx.doi.org/10.3389/fphar.2021.654699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100228PMC
April 2021

Cellulosic nanofibers filled poly(β-hydroxybutyrate): Relations between viscoelasticity of composites and aspect ratios of nanofibers.

Carbohydr Polym 2021 Aug 24;265:118093. Epub 2021 Apr 24.

School of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu Province 225002, PR China; Provincial Key Laboratories of Environmental Engineering & Materials, Yangzhou, Jiangsu Province 225002, PR China. Electronic address:

Dispersion states are vital for fibrous nanocelluloses to be used as reinforcements for polymers, which is highly dependent on geometry of nanocelluloses. Three types of nanocelluloses with various fiber aspect ratios were used to prepare target composite samples with poly(β-hydroxybutyrate) in this work. Viscoelasticity/elastoplasticity were used as probes to detect the flexibility-morphology relations of nanocelluloses in polymer. Cellulose nanocrystals (aspect ratio = 8) were rigid in polymer, retaining their rod-like shape, whereas bacterial celluloses (aspect ratio = 600) fully flexible, forming closely networked structure, and cellulose nanofibers (aspect ratio = 70) semi-flexible, dispersing as loosely flocculated clusters. Owing to these differences, the viscoelastic flow and elastoplastic deformation of three kinds of composites differed from one another. The strain-scaling and hysteresis work-scaling behaviors were then used to establish relaxation scale-structure correlations of target samples. This work provides interesting information around regulating the dispersion of nanocelluloses in polymer composites by tailoring aspect ratios of nanocelluloses.
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http://dx.doi.org/10.1016/j.carbpol.2021.118093DOI Listing
August 2021

Application effect of the hospital-community integrated service model in home rehabilitation of stroke in disabled elderly: a randomised trial.

Ann Palliat Med 2021 Apr;10(4):4670-4677

Department of Neurology, Affiliated Hospital of Jiangnan University, Wuxi, China.

Background: Disabled elderly with stroke usually have difficulty in obtaining professional rehabilitation intervention after being discharged from the hospital, and their self-health management ability is low, so their illness is prone to relapse. The hospital community-integrated service model (HCISM) is a scientific model designed to meet the needs of home care after discharge from the hospital, improve the quality of life of patients after discharge from the hospital, ease the burden on the family, and improve the service capabilities of community medical staff. The purpose of this study is to explore the effect of HCISM in home rehabilitation of stroke disabled elderly.

Methods: From September 2019 to September 2020, 120 the disabled elderly patients with stroke admitted to Affiliated hospital of Jiangnan University were selected and divided into two groups with a random number table method, with 60 cases in each group. Both groups underwent home rehabilitation after discharge, the control group was given routine intervention, and the observation group was given HCISM intervention. The changes of self-care ability, compliance behavior, self-efficacy, and adverse mood before and after intervention were compared between the two groups.

Results: The modified Barthel Index (MBI) score of the observation group after 3 months of intervention was higher than that of the control group (P<0.05). In the observation group, the changes in the proportion of medication, reasonable diet, moderate exercise, and regular return visits after 3 months were higher than those in the control group (P<0.05). The General Self-efficacy Scale (GSES) score of the observation group was higher than that of the control group after 3 months of intervention (P<0.05). Zung's Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores in the observation group were low after 3 months of intervention than those in the control group (P<0.05).

Conclusions: HCISM applied to the home rehabilitation of the disabled elderly patients with stroke can improve life self-care ability and self-efficacy, improve medical compliance behavior, and reduce negative emotions, thus making it worthy of further promotion.
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http://dx.doi.org/10.21037/apm-21-602DOI Listing
April 2021

Electrospun chitosan oligosaccharide/polycaprolactone nanofibers loaded with wound-healing compounds of Rutin and Quercetin as antibacterial dressings.

Int J Biol Macromol 2021 May 6. Epub 2021 May 6.

Center for Global Health, School of Public Health, Nanjing Medical University, 211166 Nanjing, China; The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, 211166 Nanjing, China; Jiangsu Province Engineering Research Center of Antibody Drug, Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing 211166, China. Electronic address:

Burn injury has posed devastating burdens on the public health due to its inevitable damage to the skin structure resulting in the increased risk of infection. Therefore, it is highly demanding to develop efficacious antibacterial wound-healing dressing. Despite the favourable wound-healing activities, the curative efficacy of phytochemical compounds of quercetin (Qe) and its derivatives is limited by their poor water solubility. Here, we have fabricated a novel electrospun nanofiber membrane (ENM) consisting of polycaprolactone (PCL), chitosan oligosaccharides (COS), and Qe/Rutin (Ru) as the potential bioactive dressing for wound healing. The incorporation of chitosan oligosaccharides (COSs) in the PCL scaffold at the optimized molar ratio not only contributed to the improved hydrophilicity and water absorption performance of the ENM but effectively increased the specific surface area of the formed nanofibers. In particular, the antioxidant and antibacterial activities of the Qe/rutin-loaded nanofiber membranes were tested, which revealed that the PCL-COS-Qe membrane exhibited superior performance among all nanofiber membranes. Therefore, the developed PCL-COS-Qe/Ru nanofiber membranes hold enormous potential as healthcare products, such as wound dressings for burn injuries.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.031DOI Listing
May 2021

β -Glucan Improves Protective Qi Status in Adults with Protective Qi Deficiency-A Randomized, Placebo-Controlled, and Double-Blinded Trial.

Chin J Integr Med 2021 May 8. Epub 2021 May 8.

Research and Development Department, USANA Health Science, Inc., Salt Lake City, UT, 84121, USA.

Objective: To test the hypothesis that β -glucan enhances protective qi (PQi), an important Chinese medicine (CM) concept which stipulates that a protective force circulates throughout the body surface and works as the first line of defense against "external pernicious influences".

Methods: A total of 138 participants with PQi deficiency (PQD) were randomized to receive β -glucan (200 mg daily) or placebo for 12 weeks. Participants' PQi status was assessed every 2 weeks via conventional diagnosis and a standardized protocol from which a PQD severity and risk score was derived. Indices of participants' immune and general health status were also monitored, including upper respiratory tract infection (URTI), saliva secretory IgA (sIgA), and self-reported measures of physical and mental health (PROMIS).

Results: PQi status was not significantly different between the β -glucan and placebo treatment groups at baseline but improved significantly in the β -glucan (vs. placebo) group in a time-dependent manner. The intergroup differences [95% confidence interval (CI)] in severity score (scale: 1-5), risk score (scale: 0-1), and proportion of PQD participants (%) at finish line was 0.49 (0.35-0.62), 0.48 (0.35-0.61), and 0.36 (0.25-0.47), respectively. Additionally, β -glucan improved URTI symptom (scale: 1-9) and PROMIS physical (scale: 16.2-67.7) and mental (scale: 21.2-67.6) scores by a magnitude (95% CI) of 1.0 (0.21-1.86), 5.7 (2.33-9.07), and 3.0 (20.37-6.37), respectively, over placebo.

Conclusions: β -glucan ameliorates PQi in PQD individuals. By using stringent evidence-based methodologies, our study demonstrated that Western medicine-derived remedies, such as β -glucan, can be employed to advance CM therapeutics. (ClinicalTrial.Gov registry: NCT03782974).
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http://dx.doi.org/10.1007/s11655-021-3444-0DOI Listing
May 2021

Changes in soil water holding capacity and water availability following vegetation restoration on the Chinese Loess Plateau.

Sci Rep 2021 May 7;11(1):9692. Epub 2021 May 7.

State Key Laboratory of Soil Erosion and Dryland Farming on the Loess Plateau, Institute of Soil and Water Conservation, Chinese Academy of Sciences and Ministry of Water Resources, Yangling, 712100, Shaanxi, People's Republic of China.

Changes in land use type can lead to variations in soil water characteristics. The objective of this study was to identify the responses of soil water holding capacity (SWHC) and soil water availability (SWA) to land use type (grassland, shrubland and forestland). The soil water characteristic curve describes the relationship between gravimetric water content and soil suction. We measured the soil water characteristic parameters representing SWHC and SWA, which we derived from soil water characteristic curves, in the 0-50 cm soil layer at sites representing three land use types in the Ziwuling forest region, located in the central part of the Loess Plateau, China. Our results showed that the SWHC was higher at the woodland site than the grassland and shrubland, and there was no significant difference between the latter two sites, the trend of SWA was similar to the SWHC. From grassland to woodland, the soil physical properties in the 0-50 cm soil layer partially improved, BD was significantly higher at the grassland site than at the shrubland and woodland sites, the clay and silt contents decreased significantly from grassland to shrubland to woodland and sand content showed the opposite pattern, the soil porosity was higher in the shrubland and woodland than that in the grassland, the soil physical properties across the 0-50 cm soil layer improved. Soil texture, porosity and bulk density were the key factors affecting SWHC and SWA. The results of this study provide insight into the effects of vegetation restoration on local hydrological resources and can inform soil water management and land use planning on the Chinese Loess Plateau.
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http://dx.doi.org/10.1038/s41598-021-88914-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105322PMC
May 2021

ROC1 promotes the malignant progression of bladder cancer by regulating p-IκBα/NF-κB signaling.

J Exp Clin Cancer Res 2021 May 7;40(1):158. Epub 2021 May 7.

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No.100 Haining Road, Hongkou District, Shanghai, 200080, China.

Background: Regulator of cullins 1 (ROC1) is an important catalytic subunit of cullin-RING E3 ligase. Nuclear factor-kappa B (NF-κB) signaling is closely related to tumor invasion and metastasis. Earlier, we reported that ROC1 was associated with a poor prognosis in patients with bladder cancer (BCa). However, it is unclear whether ROC1 is involved in the NF-κB signaling associated with malignant BCa progression.

Methods: The expression of ROC1 and p65 in bladder cancer and paracancerous tissues were detected by immunohistochemistry (IHC). Pearson correlation was used to assess correlation between ROC1 and p65 protein expressions. The wound-healing and transwell assays were used to monitor cell invasion and migration. The effect of ROC1 on the expression of key proteins in the NF-κB signaling was determined by immunofluorescence and western blot (WB). Cycloheximide (CHX), MG132 and immunoprecipitation assays were used to evaluate the effect of ROC1 on the ubiquitination of phosphorylated inhibitor of kappa B alpha (p-IκBα). A lung metastasis mouse model was generated to detect the role of ROC1 in tumor metastasis.

Results: We found that ROC1 was up-regulated in BCa tissues and cell lines, and high ROC1 levels were positively correlated with higher tumour grade, lymph node metastasis, distant metastasis and poor prognosis. Linear-regression analysis showed significant a Pearson correlation between ROC1 and nuclear p65 expression in BCa tissue microarray (TMA) samples. Functional studies demonstrated that ROC1 promoted BCa cell invasion and migration. In vitro and in vivo experiments showed that ROC1 activated NF-κB signaling by enhancing the ubiquitination of p-IκBα, which caused p65 nuclear translocation and promoted the transcription of some metastasis-related target genes, such as urokinase-type plasminogen activator receptor (uPAR), intracellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and matrix metalloproteinase 9 (MMP9), resulting in promoting BCa metastasis.

Conclusion: ROC1 plays an important role in the progression of BCa and serves as a potential diagnostic and therapeutic target for patients with BCa.
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http://dx.doi.org/10.1186/s13046-021-01935-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106150PMC
May 2021

Prognostic value of members of NFAT family for pan-cancer and a prediction model based on NFAT2 in bladder cancer.

Aging (Albany NY) 2021 May 7;13. Epub 2021 May 7.

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, Hubei, P.R. China.

Bladder cancer (BLCA) is one of the common malignant tumors of the urinary system. The poor prognosis of BLCA patients is due to the lack of early diagnosis and disease recurrence after treatment. Increasing evidence suggests that gene products of the nuclear factor of activated T-cells (NFAT) family are involved in BLCA progression and subsequent interaction(s) with immune surveillance. In this study, we carried out a pan-cancer analysis of the NFAT family and found that NFAT2 is an independent prognostic factor for BLCA. We then screened for differentially expressed genes (DEGs) and further analyzed such candidate gene loci using gene ontology enrichment to curate the KEGG database. We then used Lasso and multivariate Cox regression to identify 4 gene loci (FER1L4, RNF128, EPHB6, and FN1) which were screened together with NFAT2 to construct a prognostic model based on using Kaplan-Meier analysis to predict the overall survival of BLCA patients. Moreover, the accuracy of our proposed model is supported by deposited datasets in the Gene Expression Omnibus (GEO) database. Finally, a nomogram of this prognosis model for BLCA was established which could help to provide better disease management and treatment.
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http://dx.doi.org/10.18632/aging.202982DOI Listing
May 2021

Primary ciliated muconodular papillary tumor: A rare pulmonary disease and literature review of 65 cases.

Thorac Cancer 2021 May 7. Epub 2021 May 7.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

A ciliated muconodular papillary tumor (CMPT) or bronchiolar adenoma (BA) is a rather rare and unique type of lung tumor characterized by tripartite cellular components with a papillary-predominant structure including ciliated columnar cells, mucinous cells, and basal cells. Here, we present the case of a 64-year-old woman who was diagnosed with CMPT in our center. In addition to reporting the clinicopathological characteristics of this case, we also conducted whole exome sequencing (WES) to explore the underlying mechanism. According to current evidence, CMPTs tends to be benign or of low grade malignancy. However, this requires further validation.
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http://dx.doi.org/10.1111/1759-7714.13963DOI Listing
May 2021

PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial ischemia/reperfusion injury.

J Mol Histol 2021 May 5. Epub 2021 May 5.

Department of Thoracic Surgery, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

Myocardial ischemia/reperfusion (I/R) injury induces cardiomyocyte apoptosis to deteriorate heart function. Thus, how to inhibit cardiomyocyte apoptosis is the focus of recent researches. Proteasome family member PSMB4 (proteasome subunit beta type-4) promotes cell survival. The relationship between PSMB4 and cardiomyocyte apoptosis during myocardial I/R is unknown. In this study, PSMB4 expression increased in rat myocardial I/R model, positively correlated with cleaved caspase-3 expression, negatively correlated with Bcl-2 expression. In vitro, neonatal ventricle cardiomyocyte hypoxia/reoxygenation (H/R) model was constructed to mimic myocardial I/R. PSMB4 silence promoted cardiomyocyte apoptosis and IκBα expression, inhibited the activation of NF-κB. On the contrary, PSMB4 overexpession inhibited cardiomyocyte apoptosis and IκBα expression, promoted the activation of NF-κB. Additionally, PSMB4-IκBα interaction was identified, suggesting that PSMB4 might participate in the proteasome dependent degradation of IκBα. The data indicates that PSMB4 inhibits cardiomyocyte apoptosis via activating NF-κB signaling pathway during myocardial I/R, which can supply novel molecular target for the treatment of ischemic heart disease.
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http://dx.doi.org/10.1007/s10735-021-09977-xDOI Listing
May 2021

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model.

Sci Rep 2021 05 5;11(1):9609. Epub 2021 May 5.

Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a M inhibitor with antiviral activity against SARS-CoV-2 in vitro. Using the K18-hACE2 mouse model, the in vivo antiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice. Overall outcome of clinical symptoms and survival upon SARS-CoV-2 challenge were not improved in mice treated with GC-376 compared to controls. The treatment with GC-376 slightly improved survival from 0 to 20% in mice challenged with a high virus dose at 10 TCID50/mouse. Most notably, GC-376 treatment led to milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls in mice challenged with a low virus dose at 10 TCID50/mouse. This was particularly the case in the brain where a 5-log reduction in viral titers was observed in GC-376 treated mice compared to vehicle controls. This study supports the notion that GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection and that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2.
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http://dx.doi.org/10.1038/s41598-021-89013-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100161PMC
May 2021

ALPPS in the treatment of liver cancer with insufficient future liver remnant.

Hepatobiliary Pancreat Dis Int 2021 Apr 16. Epub 2021 Apr 16.

Department of Surgery, Third Central Hospital of Tianjin (Third Central Clinical College of Tianjin Medical University), Tianjin 300170, China; Tianjin Institute of Hepatobiliary Disease, Tianjin 300170, China; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin 300170, China; Artificial Cell Engineering Technology Research Center, Tianjin 300170, China.

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http://dx.doi.org/10.1016/j.hbpd.2021.04.003DOI Listing
April 2021

Clinical Effect of Different Drugs and Infusion Techniques for Patient-Controlled Analgesia After Spinal Tumor Surgery: A Prospective, Randomized, Controlled Clinical Trial.

Clin Ther 2021 May 2. Epub 2021 May 2.

Department of Anaesthesiology, First Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province, China. Electronic address:

Purpose: To evaluate the outcomes of the different drug combination and infusion techniques for patient-controlled analgesia (PCA).

Methods: Ninety-seven patients who had undergone spinal tumor surgery were randomized to 4 groups with different PCA drugs and infusion techniques: subcutaneous sufentanil (SS) group; (n=25), subcutaneous sufentanil and dexmedetomidine (SDS) group (n=24), intravenous sufentanil (SI) group (n=23), and intravenous sufentanil and dexmedetomidine (SDI) group (n=25). The primary outcome measured the cumulative amount of sufentanil delivered to the patients through PCA 24 and 48 hours after the surgery. Secondary outcomes measured the visual analog scale pain scores 24 and 48 hours after the surgery, Pittsburgh Sleep Quality Index before and 1 month after surgery, Athens Insomnia Score before and the first 2 nights after surgery, and the rate of adverse events within 48 hours after surgery.

Findings: At 24 and 48 hours after surgery, the cumulative amount of sufentanil in the SDS group (mean [SD], 76.44 [10.75] at 24 hours and 151.96 [20.92] at 48 hours) and the SDI group (mean [SD], 75.08 [9.00] at 24 hours and 149.56 [18.22] at 48 hours) were significantly lower than in SS group (mean [SD] 95.52 [12.40] at 24 hours and 183.23 [23.06] at 48 hours) and the SI group (mean [SD], 97.25 [10.80] at 24 hours and 186.67 [20.14] at 48 hours; P < 0.001). The visual analog scale pain scores and Athens Insomnia Scale scores were also lower in the SDS and SDI groups than in the SS and SI groups 24 and 48 hours after surgery (P < 0.05). The Pittsburgh Sleep Quality Index was lower in the SDS and SDI groups 1 month after surgery. Lastly, the rate of nausea and vomiting was higher in the SI group than in the SS, SDS, and SDI groups (P = 0.018).

Implications: Dexmedetomidine in PCA could decrease sufentanil intake and improve analgesic effect and sleep quality. Subcutaneous PCA can provide the same benefit with a lower rate of nausea and vomiting. ClinicalTrials.gov identifier: NCT04111328. (Clin Ther. 2021;XX:XXX-XXX) © 2021 Elsevier HS Journals, Inc.
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http://dx.doi.org/10.1016/j.clinthera.2021.03.019DOI Listing
May 2021

Nintedanib attenuates peritoneal fibrosis by inhibiting mesothelial-to-mesenchymal transition, inflammation and angiogenesis.

J Cell Mol Med 2021 May 5. Epub 2021 May 5.

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Nintedanib, an Food and Drug Administration (FDA) approved multiple tyrosine kinase inhibitor, exhibits an anti-fibrotic effect in lung and kidneys. Its effect on peritoneal fibrosis remains unexplored. In this study, we found that nintedanib administration lessened chlorhexidine gluconate (CG)-induced peritoneal fibrosis and reduced collagen I and fibronectin expression. This coincided with suppressed phosphorylation of platelet-derived growth factor receptor, fibroblast growth factor receptors, vascular endothelial growth factor receptor and Src family kinase. Mechanistically, nintedanib inhibited injury-induced mesothelial-to-mesenchymal transition (MMT), as demonstrated by decreased expression of α-smooth muscle antigen and vimentin and preserved expression of E-cadherin in the CG-injured peritoneum and cultured human peritoneal mesothelial cells exposed to transforming growth factor-β1. Nintedanib also suppressed expression of Snail and Twist, two transcription factors associated with MMT in vivo and in vitro. Moreover, nintedanib treatment inhibited expression of several cytokines/chemokines, including tumour necrosis factor-α, interleukin-1β and interleukin-6, monocyte chemoattractant protein-1 and prevented infiltration of macrophages to the injured peritoneum. Finally, nintedanib reduced CG-induced peritoneal vascularization. These data suggest that nintedanib may attenuate peritoneal fibrosis by inhibiting MMT, inflammation, and angiogenesis and have therapeutic potential for the prevention and treatment of peritoneal fibrosis in patients on peritoneal dialysis.
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http://dx.doi.org/10.1111/jcmm.16518DOI Listing
May 2021

Potential Therapeutic Targets of Obesity-Related Glomerulopathy.

Metab Syndr Relat Disord 2021 May 3. Epub 2021 May 3.

Department of Endocrinology, Baoding NO.1 Central Hospital, Baoding, Hebei, People's Republic of China.

The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. The purpose of this review is to emphasize the potential therapeutic targets of ORG as well as the corresponding possible mechanisms. We systematically identified surveys, reports, and published studies that included data for the purpose of this review and did literature analysis. Under circumstance of obesity, weight loss, and renin-angiotensin-aldosterone blockade are the most studied therapies, effective to induce antiproteinuric effects and reversal of hyperfiltration in ORG. Glucagon-like peptide-1-based therapies led to improvement in proteinuria. Newer therapies directed to lipid metabolism, including farnesoid X receptor and takeda G protein-coupled receptor 5 agonists, peroxisome proliferator-activated receptor α agonists, hold therapeutic promise. Prevention and treatments of obesity and ORG are of great importance.
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http://dx.doi.org/10.1089/met.2020.0141DOI Listing
May 2021

An effective self-supervised framework for learning expressive molecular global representations to drug discovery.

Brief Bioinform 2021 May 3. Epub 2021 May 3.

Tsinghua Laboratory of Brain and Intelligence and Department of Biomedical Engineering, Tsinghua University, Haidian, 100084 Beijing, China.

How to produce expressive molecular representations is a fundamental challenge in artificial intelligence-driven drug discovery. Graph neural network (GNN) has emerged as a powerful technique for modeling molecular data. However, previous supervised approaches usually suffer from the scarcity of labeled data and poor generalization capability. Here, we propose a novel molecular pre-training graph-based deep learning framework, named MPG, that learns molecular representations from large-scale unlabeled molecules. In MPG, we proposed a powerful GNN for modelling molecular graph named MolGNet, and designed an effective self-supervised strategy for pre-training the model at both the node and graph-level. After pre-training on 11 million unlabeled molecules, we revealed that MolGNet can capture valuable chemical insights to produce interpretable representation. The pre-trained MolGNet can be fine-tuned with just one additional output layer to create state-of-the-art models for a wide range of drug discovery tasks, including molecular properties prediction, drug-drug interaction and drug-target interaction, on 14 benchmark datasets. The pre-trained MolGNet in MPG has the potential to become an advanced molecular encoder in the drug discovery pipeline.
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http://dx.doi.org/10.1093/bib/bbab109DOI Listing
May 2021

Clinicopathological Features and Prognoses in Patients With Brain Metastases From Small-Cell Esophageal Carcinoma: A Retrospective Analysis of 18 Patients.

Front Oncol 2021 16;11:654727. Epub 2021 Apr 16.

Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

This study aims to examine the clinical characteristics of patients with brain metastases (BM) from small-cell esophageal carcinoma (SCEC) and to explore the association of the corresponding factors with overall survival (OS). The data of 18 patients with brain metastases from SCEC, diagnosed from January 1, 2006, to December 31, 2018, in the Fourth Hospital of Hebei Medical University were analyzed retrospectively. The 18 patients who were included in this study accounted for 6.7% of the patients with SCEC diagnosed from 2006 to 2018. Of the 18 patients, 8 (44.4%) were females. For the entire cohort, the median OS was 7 months, the 1-year OS was 22.2%, and the 2-year OS was 0%. For patients who received whole-brain radiotherapy (WBRT) and for those who did not (13 vs. 5), the median OS was 11.9 and 3 months, respectively, and the 1-year OS was 30.8 and 0%, respectively. When comparing diagnosis-specific Graded Prognostic Assessment (DS-GPA) scores of patients with BM from SCEC ranging from 2.5 to 4 and from 0 to 2, the median OS was 13.1 and 4 months, respectively, and the 1-year OS was 57.1 and 0%, respectively. In the univariable regression, patients who received WBRT had improved OS compared to those who did not (HR = 0.249, = 0.018), and patients with a DS-GPA score of 2.5-4 were associated with improved OS compared with patients with a DS-GPA score of 0-2 (HR = 0.050, = 0.005). The incidence of brain metastases in patients with SCEC is low, but the prognosis in those patients is very poor. The DS-GPA score may be a prognostic factor of patients with BM from SCEC. Brain radiotherapy could improve the survival of these patients.
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http://dx.doi.org/10.3389/fonc.2021.654727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085384PMC
April 2021

Predicted Disease-Specific Immune Infiltration Patterns Decode the Potential Mechanisms of Long Non-Coding RNAs in Primary Sjogren's Syndrome.

Front Immunol 2021 14;12:624614. Epub 2021 Apr 14.

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Primary Sjogren's syndrome (pSS) is a chronic progressive autoimmune disease with clinical phenotypic "Sicca symptoms". In some cases, the diagnosis of pSS is delayed by 6-7 years due to the inefficient differential diagnosis of pSS and non-SS "Sicca". This study aimed to investigate the difference between these two diseases, and in particular, their immunopathogenesis. Based on their gene expression profiles, we systematically defined for the first time the predicted disease-specific immune infiltration pattern of patients with pSS differentiated from normal donors and patients with non-SS "Sicca". We found that it was characterized by the aberrant abundance and interaction of tissue-infiltrated immune cells, such as a notable shift in the subpopulation of six immune cells and the perturbed abundance of nine subpopulations, such as CD4+ memory, CD8+ T-cells and gamma delta T-cells. In addition, we identified essential genes, particularly long non-coding RNAs (lncRNAs), as the potential mechanisms linked to this predicted pattern reprogramming. Fourteen lncRNAs were identified as the potential regulators associated with the pSS-specific immune infiltration pattern in a synergistic manner, among which the lncRNA was highly relevant to chemokine signaling pathways. In conclusion, aberrant predicted disease-specific immune infiltration patterns and relevant genes revealed the immunopathogenesis of pSS and provided some clues for the immunotherapy by targeting specific immune cells and genes.
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http://dx.doi.org/10.3389/fimmu.2021.624614DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079748PMC
April 2021

Two Small Extracellular Vesicle sRNAs Derived From Serve as Diagnostic Biomarkers for Active Pulmonary Tuberculosis.

Front Microbiol 2021 15;12:642559. Epub 2021 Apr 15.

Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

The rapid diagnosis of tuberculosis (TB) is of great significance for the control and treatment of TB. However, TB remains a major healthy, social, and economic burden worldwide because of the lack of ideal diagnostic biomarkers. encoded small RNA (sRNA) is a class of regulation small RNA. Several studies have identified encoded-sRNAs in the serum/plasm of infected patients. Small extracellular vesicles are small membrane vesicles secreted by many cell types during physiological and pathological conditions. Recent evidence has indicated that most of the nucleic acids in the serum/plasma are packaged in the small extracellular vesicles and could serve as ideal diagnostic biomarkers. In this study, we attempted a novel approach for TB diagnosis: targeting small extracellular vesicles encoded sRNA (sRNA) by qRT-PCR. The results showed that encoded ASdes and MTB-miR5 only existed in tuberculosis patients and have the potential to serve as a sensitive and accurate methodology for TB diagnosis.
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http://dx.doi.org/10.3389/fmicb.2021.642559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082067PMC
April 2021

Facile synthesis of iron oxide supported on porous nitrogen doped carbon for catalytic oxidation.

Sci Total Environ 2021 Apr 24;785:147296. Epub 2021 Apr 24.

School of Chemical Engineering and Technology, Tianjin University, Tianjin 300050, China. Electronic address:

Iron oxide (FeO) supported on porous nitrogen doped carbon is synthesized by a facile pyrolysis method. SiO and NaNO are used as the template and activation agent respectively for porous structure generation and large specific surface area (SSA) creation. The obtained materials show superior catalytic oxidation ability and can activate peroxymonosulfate (PMS) in a wide pH range (3-9) to degrade organic pollutants. The degradation process is a two-stage reaction, including a rapid initial decay and a following slow reaction stage. According to the free radical quenching experiments, electron paramagnetic resonance (EPR) spectroscopy analysis, and electrochemical tests, the superoxide radical (O) and singlet oxygen (O) are proved to play crucial roles in organics degradation. The high SSA (773 m g), abundant of structural defects, and synergistic effect between FeO and the nitrogen doped carbon are the key factors for the enhanced activity. The catalysts in this study can be synthesized easily and contain no toxic metals, thus should have great potential in the wastewater remediation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147296DOI Listing
April 2021

Neuromodulatory effect of interleukin 1β in the dorsal raphe nucleus on individual differences in aggression.

Mol Psychiatry 2021 Apr 30. Epub 2021 Apr 30.

Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Heightened aggressive behavior is considered as one of the central symptoms of many neuropsychiatric disorders including autism, schizophrenia, and dementia. The consequences of aggression pose a heavy burden on patients and their families and clinicians. Unfortunately, we have limited treatment options for aggression and lack mechanistic insight into the causes of aggression needed to inform new efforts in drug discovery and development. Levels of proinflammatory cytokines in the periphery or cerebrospinal fluid were previously reported to correlate with aggressive traits in humans. However, it is still unknown whether cytokines affect brain circuits to modulate aggression. Here, we examined the functional role of interleukin 1β (IL-1β) in mediating individual differences in aggression using a resident-intruder mouse model. We found that nonaggressive mice exhibit higher levels of IL-1β in the dorsal raphe nucleus (DRN), the major source of forebrain serotonin (5-HT), compared to aggressive mice. We then examined the effect of pharmacological antagonism and viral-mediated gene knockdown of the receptors for IL-1 within the DRN and found that both treatments consistently increased aggressive behavior of male mice. Aggressive mice also exhibited higher c-Fos expression in 5-HT neurons in the DRN compared to nonaggressive mice. In line with these findings, deletion of IL-1 receptor in the DRN enhanced c-Fos expression in 5-HT neurons during aggressive encounters, suggesting that modulation of 5-HT neuronal activity by IL-1β signaling in the DRN controls expression of aggressive behavior.
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http://dx.doi.org/10.1038/s41380-021-01110-4DOI Listing
April 2021

MIR99AHG is a noncoding tumor suppressor gene in lung adenocarcinoma.

Cell Death Dis 2021 Apr 30;12(5):424. Epub 2021 Apr 30.

Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.

Little is known about noncoding tumor suppressor genes. An effective way to identify these genes is by analyzing somatic copy number variation (CNV)-related noncoding genes. By integrated bioinformatics analyses of differentially expressed long noncoding RNAs (lncRNAs) and arm-level CNVs in lung adenocarcinoma (LUAD), we identified a potential antitumor gene, MIR99AHG, encoding lncRNA MIR99AHG as well as a miR-99a/let-7c/miR-125b2 cluster on chromosome 21q. All four of these transcripts were downregulated in LUAD tissues partly due to the copy number deletion of the MIR99AHG gene. Both MIR99AHG and miR-99a expression was positively correlated with the survival of LUAD patients. MIR99AHG suppressed proliferation and metastasis and promoted autophagy both in vitro and in vivo. Mechanistically, the interaction between MIR99AHG and ANXA2 could accelerate the ANXA2-induced ATG16L vesicle biogenesis, thus promoting phagophore assembly. Additionally, miR-99a targeted a well-known autophagy suppressor, mammalian target of rapamycin (mTOR), thereby synergistically promoting autophagy and postponing LUAD progression with MIR99AHG. In summary, MIR99AHG emerges as a noncoding tumor suppressor gene in LUAD, providing a new strategy for antitumor therapy.
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http://dx.doi.org/10.1038/s41419-021-03715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087685PMC
April 2021

Acute high-grade acromioclavicular joint dislocation patients treated with titanium cable insertion under a homemade guider.

J Orthop Surg Res 2021 Apr 30;16(1):287. Epub 2021 Apr 30.

Department of Orthopedic, Xiaoshan First People's Hospital, Xiaoshan Affiliated Hospital of Wenzhou Medical University, No. 199 Shixin Road, Hangzhou, 311200, Zhejiang Province, China.

Backgrounds: To describe a new technique for implanting a double-bundle titanium cable to treat acromioclavicular (AC) joint dislocation via the new guider, and evaluate clinic outcomes.

Methods: A retrospective study of patients treated for acute high-grade acromioclavicular joint dislocation from June 2016 to January 2020 in our trauma center, twenty patients with AC joint dislocation were managed with double-bundle titanium cable. It includes the following steps: (1) Put the guider under the coracoid close to the cortical; (2) drill proximal clavicle; (3) place the titanium cable; (4) perforate distal clavicle, (5) reset the acromioclavicular joint and lock titanium cable; and (6) suture the acromioclavicular ligament. An independent reviewer conducted functional testing of these patients, including the use of coracoclavicular distance (CCD), visual analog scale (VAS) scores, and Constant-Murley scores (CMS).

Results: All patients are presented following at a median duration of 15 months (12-24months) after the surgery. All patients based on X-ray evaluation and clinic evaluation. The median CCD was 7.5 (6-14) mm, the VAS score was 0.55 (0-2), the CMS score was 95.5 (92-99). One patient had subluxation again at the final follow-up based on X-ray examination.

Conclusions: This study demonstrates that the AC joint fixation anatomically with double-bundle titanium, acquired excellent outcomes in terms of the recovery of shoulder joint function and radiographic outcomes. It has a low complication rate and need not remove the hardware.
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http://dx.doi.org/10.1186/s13018-021-02442-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086091PMC
April 2021