Publications by authors named "Cheng Huang"

1,352 Publications

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Comparing Patient-Controlled Analgesia Versus Non-PCA Hydromorphone Titration for Severe Cancer Pain: A Randomized Phase III Trial.

J Natl Compr Canc Netw 2021 Aug 3:1-8. Epub 2021 Aug 3.

Department of Medical Oncology, Xiamen Humanity Hospital and Fujian Medical University Xiamen Humanity Hospital, Xiamen.

Background: Opioid titration is necessary to achieve rapid, safe pain relief. Medication can be administered via patient-controlled analgesia (PCA) or by a healthcare provider (non-PCA). We evaluated the efficacy of intravenous PCA versus non-PCA hydromorphone titration for severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]).

Patients And Methods: Patients with severe cancer pain were randomized 1:1 to PCA or non-PCA titration, stratified by opioid-tolerant or opioid-naïve status. The PCA pump was set to no continuous dose, with a hydromorphone bolus dose 10% to 20% of the total previous 24-hour equianalgesic (for opioid-tolerant patients) or 0.5 mg (for opioid-naïve patients). For the non-PCA group, the initial hydromorphone bolus dose was identical to that in the PCA group, with the subsequent dose increased by 50% to 100% (for NRS unchanged or increased) or repeated at the current dose (for NRS 4-6). Hydromorphone delivery was initiated every 15 minutes (for NRS ≥4) or as needed (for NRS ≤3). The primary endpoint was time to successful titration (TST; time from first hydromorphone dose to first occurrence of NRS ≤3 in 2 consecutive 15-minute intervals).

Results: Among 214 patients (PCA, n=106; non-PCA, n=108), median TSTs (95% CI) were 0.50 hours (0.25-0.50) and 0.79 hours (0.50-1.42) for the PCA and non-PCA groups, respectively (hazard ratio [HR], 1.64; 95% CI, 1.23-2.17; P=.001). TSTs in opioid-tolerant patients were 0.50 hours (0.25-0.75) and 1.00 hours (0.50-2.00) for the PCA and non-PCA groups, respectively (HR, 1.92; 95% CI, 1.32-2.78; P=.003); in opioid-naive patients, TST was not significantly different for the PCA versus non-PCA groups (HR, 1.35; 95% CI, 0.88-2.04; P=.162). Pain score (median NRS; interquartile range) over 24 hours was significantly lower in the PCA group (2.80; 2.15-3.22) than in the non-PCA group (3.00; 2.47-3.53; P=.020). PCA administration produces significantly higher patient satisfaction with pain control than non-PCA administration (P<.001).

Conclusions: Intravenous hydromorphone titration for severe cancer pain was achieved more effectively with PCA than with non-PCA administration.
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http://dx.doi.org/10.6004/jnccn.2020.7699DOI Listing
August 2021

A magnified aptamer fluorescence sensor based on the metal organic frameworks adsorbed DNA with enzyme catalysis amplification for ultra-sensitive determination of ATP and its logic gate operation.

Bioorg Chem 2021 May 26;114:105020. Epub 2021 May 26.

College of Chemistry and Chemical Engineering, Southwest Petroleum University, Chengdu 610500, People's Republic of China.

With the development of frame materials, metal organic frameworks (MOFs) have been successfully applied in the fields of biological small molecule analysis and fluorescent DNA detection. In this work, in view of the good adsorption characteristics of MIL-101(Cr), the highly sensitive detection of adenosine triphosphate (ATP) assisted nucleic acid exonuclease amplification by MIL-101(Cr) on the different affinity of single stranded DNA and double stranded DNA was investigated. The detection limit of ATP reaches 1.7 μM, and the platform has good applicability in biological samples. On this basis, an "AND" logic gate was successfully constructed. Superior sensitivity to ATP in the presence of exonuclease was reflected, which greatly enhanced the system's fluorescence. Importantly, the fluorescence sensing application of this nanomaterial inspired other target detection and enriched the building blocks of fluorescence sensing platform.
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http://dx.doi.org/10.1016/j.bioorg.2021.105020DOI Listing
May 2021

Association between the inclination angle of the proximal tibiofibular joint surface and medial compartment knee osteoarthritis.

Ann Palliat Med 2021 Jul 27. Epub 2021 Jul 27.

PLA Institute of Orthopaedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Background: Fibular support for the lateral tibial plateau through the proximal tibiofibular joint (PTFJ) results in nonuniform settlement of the tibial plateau in middle-aged and elderly persons and may lead to medial compartment knee osteoarthritis. However, the inclination angle of the PTFJ surface varies widely and may affect nonuniform settlement. The purpose of this case-control study was to assess the association between the inclination angle of the PTFJ surface and medial compartment knee osteoarthritis.

Methods: The fibular inclination angle (FIA) and tibial inclination angle (TIA) of the PTFJ surface were measured using radiographs. Differences of FIA and TIA among groups were assessed with t tests and the odds ratios (ORs) for risk factors of medial compartment knee osteoarthritis were calculated with binary logistic regression analysis.

Results: Forty patients and 40 control participants were included in this case-control study. Patients had both a lower FIA (P=0.005) and TIA (P=0.000) than the controls, and logistic regression analysis showed that FIA (OR =7.000) and TIA (OR =17.000) were risk factors for medial compartment knee osteoarthritis.

Conclusions: A lower inclination angle of the PTFJ surface is associated with a risk of medial compartment knee osteoarthritis. Clinically, early prevention of medial compartment knee osteoarthritis should be considered for middle-aged and elderly persons with low PTFJ inclination angles.
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http://dx.doi.org/10.21037/apm-21-1348DOI Listing
July 2021

A Novel Nomogram for Predicting Poor 6-Month Function in Patients With Acute Ischemic Stroke Receiving Thrombolysis.

J Cardiovasc Nurs 2021 Jul 26. Epub 2021 Jul 26.

Lihong Huang, MD Registered Nurse, Chongqing Medical University, People's Republic of China. Feng Li, MD Assistant Professor, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China. Cheng Huang, MD Assistant Professor, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China. Yetao Luo, MD Senior Biostatistician, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China. Guangwei Liu, MD Professor, Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, People's Republic of China.

Background: Patients with acute ischemic stroke (AIS) receiving thrombolysis with good function at discharge are usually ignored. Their functional deterioration after discharge not only compromises the effectiveness of thrombolytic therapy but also reduces their long-term quality of life, which is not conducive to the advancement of medical healthcare and continuing care.

Objective: The aims of this study were to explore the risk factors for poor 6-month function in patients with AIS receiving thrombolysis with good function at discharge and construct a novel nomogram model.

Methods: This case-control study retrospectively analyzed the medical data of 149 patients with AIS receiving thrombolysis with good function at discharge from January 2017 to June 2019. Patients were divided into a poor function group (<3 points) and a good function group (≥3 points) according to their modified Rankin Scale scores at 6 months. Logistic regression was used to identify risk factors for poor 6-month function. A novel nomogram prediction model for poor 6-month function was constructed, and its prediction performance and concordance were evaluated.

Results: Of 149 patients, 21 (14%) had poor 6-month function and 128 (86%) had good 6-month function. Multivariate regression analysis showed that physical inactivity, neutrophil count, cerebral small vessel disease score, and hospitalization days were independent risk factors for poor 6-month function. A regression model was established according to the multivariate analysis, and the area under the curve was 0.9363. The accuracy was 71.99%, the sensitivity was 78.83%, and the specificity was 70.26%. A nomogram model was constructed, and its concordance index was 0.836 after internal validation.

Conclusion: The novel nomogram model facilitates risk prediction of poor 6-month function in patients with AIS receiving thrombolysis with good function at discharge and is helpful for making discharge plans.
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http://dx.doi.org/10.1097/JCN.0000000000000843DOI Listing
July 2021

CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.

Circular RNAs (circRNAs) are a class of regulatory RNAs with complex roles in healthy and diseased tissues. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) remains poorly understood, including the mechanisms by which the circular ubiquitin binding associated protein 2 (circUBAP2) contributes to tumorigenesis. We analyzed the expression of circUBAP2 in 20 paired samples of HCC and healthy tissue as well as in seven HCC cell lines via quantitative real-time polymerase chain reaction (qRT-PCR). Functional experiments, such as CCK8 viability assays, colony formation assays, wound healing, transwell assays, and flow cytometry, were conducted to assess the effects of circUBAP2 in vitro. To further elucidate the mechanisms by which circUBAP2 acts, we conducted dual-luciferase assays, western blots, RNA pull-down assays, and rescue experiments. CircUBAP2 was highly upregulated in most HCC tissues and was associated with poor prognosis. HCC patients with high circUBAP2 expression had greater vascular invasion and worse differentiation. Functionally, circUBAP2 overexpression enhanced HCC cell proliferation, migration, and invasion and inhibited apoptosis. Furthermore, we found that circUBAP2 upregulated c-Myc expression by sponging miR-1294, thus contributing to hepatocarcinogenesis. Inhibiting circUBAP2 expression in HCC attenuated the oncogenic effects of c-Myc. These findings suggest that circUBAP2 promotes HCC growth and metastasis. CircUBAP2 may have value as an independent prognostic biomarker or as a new target for the treatment of HCC.
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http://dx.doi.org/10.1093/carcin/bgab068DOI Listing
July 2021

[Characteristics and Control Strategies on Summertime Peak Ozone Concentration in Shanghai].

Huan Jing Ke Xue 2021 Aug;42(8):3577-3584

State Environmental Protection Key Laboratory of Formation and Prevention of the Urban Air Complex, Shanghai Academy of Environmental Sciences, Shanghai 200233, China.

With the continuous development of air pollution control measures, the concentration of PM in Shanghai has shown a conspicuous downward trend in recent years. However, frequent O pollution events have highlighted the urgent need to explore the occurrence patterns of O pollution and develop scientific strategies for reducing O peaks. This study examines data from July 2017, when the cumulative number of O pollution days in 17 cities in the Yangtze River Delta was 165 days, of which Shanghai was the most serious, with an exceedance rate of 64.5%. During this period, the average concentration of NO in Shanghai was 27.1 μg·m and volatile organic copunds (VOCs) mixing ratio was 22.5×10. By analyzing ozone precursor concentrations and meteorological factors, we determined that these events mainly resulted from a combination of unfavorable meteorological conditions such as high temperature, low humidity, low wind speed, and high precursor emissions. WRF-CMAQ scenario simulations showed that a reduction in precursor emissions in Shanghai alone would have a limited controlling effect on regional O pollution. Thus, regional joint control is recommended when widespread pollution events occur. Our analysis shows that if VOCs in Shanghai and nine neighboring cities can be reduced by 30%, the maximum 8-h O concentration in Shanghai could be reduced by 7.2%. If the reduction number of these cities rises to 17, the maximum 8-h O concentration reduction rate in Shanghai will increase to 7.8%. It is also recommended that the VOCs:NO reduction ratio should be strictly controlled at more than 3:1, or else the O concentration in some areas will increase.
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http://dx.doi.org/10.13227/j.hjkx.202011243DOI Listing
August 2021

Combination Foretinib and Anti-PD-1 Antibody Immunotherapy for Colorectal Carcinoma.

Front Cell Dev Biol 2021 8;9:689727. Epub 2021 Jul 8.

State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. However, the overall response rate to immune checkpoint inhibitor therapy for many cancers is only between 20 and 40%, and even less for colorectal cancer (CRC) patients. Thus, there is an urgent need to develop an efficient immunotherapeutic strategy for CRC. Here, we developed a novel CRC combination therapy consisting of a multiple receptor tyrosine kinase inhibitor (Foretinib) and anti-PD-1 antibody. The combination therapy significantly inhibited tumor growth in mice, led to improved tumor regression without relapse (83% for CT26 tumors and 50% for MC38 tumors) and prolonged overall survival. Mechanistically, Foretinib caused increased levels of PD-L1 via activating the JAK2-STAT1 pathway, which could improve the effectiveness of the immune checkpoint inhibitor. Moreover, the combination therapy remodeled the tumor microenvironment and enhanced anti-tumor immunity by further increasing the infiltration and improving the function of T cells, decreasing the percentage of tumor-associated macrophages (TAMs) and inhibiting their polarization toward the M2 phenotype. Furthermore, the combination therapy inhibited the metastasis of CT26-Luc tumors to the lung in BALB/c mouse by reducing proportions of regulatory T-cells, TAMs and M2 phenotype TAMs in their lungs. This study suggests that a novel combination therapy utilizing both Foretinib and anti-PD-1 antibody could be an effective combination strategy for CRC immunotherapy.
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http://dx.doi.org/10.3389/fcell.2021.689727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298272PMC
July 2021

Trifluoro-icaritin alleviates mechanical hypersensitivity and improves motor coordination and balance in rats with spared nerve injury-induced neuropathic pain.

Neurosci Lett 2021 Jul 22;761:136125. Epub 2021 Jul 22.

Department of Physiology, School of Basic Medicine Sciences, Gannan Medical University, Ganzhou 341000, PR China; Pain Medicine Research Institute, Gannan Medical University, Ganzhou 341000, PR China. Electronic address:

Neuropathic pain is still one of the unsolved public health problems worldwide. Although the current reagents can attenuate neuropathic pain to a certain extent, their clinical application is very limited owing to larger toxicity and serious side effects. Trifluoro-icaritin (ICTF) has been documented to possess profound anti-inflammatory and neuroprotective activities, but whether ICTF exerts an anti-nociceptive effect on neuropathic pain remains unknown. Here, a rat model of spared nerve injury (SNI)-induced neuropathic pain was used. SNI rats were administrated with ICTF (i.p.) once daily lasting for 21 days, and subsequently the pain-related behaviors were evaluated by applying mechanical or thermal pain threshold, CatWalk gait parameter, and rotarod test on day 1 before and day 1, 3, 7, 10, 14, and 21 after SNI surgery, respectively. The results showed that ICTF (0.5 mg/kg, 1.5 mg/kg, and 5.0 mg/kg, i.p.) treatment alleviated SNI-induced mechanical allodynia but not thermal hyperalgesia in a dose-dependent manner. After administration of ICTF at the most effective dose of 5.0 mg/kg to SNI rats, CatWalk gait analysis revealed that ICTF not only significantly enhanced gait parameters including max contact max intensity, max intensity, print area, and stand time but also decreased the swing time; Rotarod test further exhibited that ICTF could effectively prolong the time on rod and increase the rotating speed in SNI rats. Additionally, following ICTF (5.0 mg/kg) treatment of SNI rats for 21 consecutive days, the max contact max intensity was found to be positively correlated with the rotating speed. Taken together, ICTF successfully ameliorates mechanical hypersensitivity and improves the motor coordination and balance in SNI rats, suggesting that ICTF may be exploited as a potential candidate in the management of neuropathic pain.
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http://dx.doi.org/10.1016/j.neulet.2021.136125DOI Listing
July 2021

Cu-modified MOF as laccase-mimicking material for colorimetric determination and discrimination of phenolic compounds with 4-aminoantipyrine.

Mikrochim Acta 2021 Jul 24;188(8):272. Epub 2021 Jul 24.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, People's Republic of China.

Based on the laccase-mimicking activity of Cu-modified University of Oslo (UiO) metal-organic framework (UiO-67-Cu), we developed a colorimetric sensor array for distinguishing a series of phenols with different number and position of substituted hydroxyl group (-OH) and different substituent group on the benzene ring, including phenol, catechol, quinol, resorcinol, pyrogallol, phloroglucinol, o-chlorophenol, o-aminophenol, and o-nitrophenol. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of phenolic compounds were obtained by theoretical calculation. The results show that the lower the LUMO energy level, the easier the chromogenic reaction occurs. The UiO-67-Cu-catalyzed phenol chromogenic reaction showed a good linearity in the range from 0.1 to 200 μM with limit of detection approximately 61 nM. Through the detection of phenol in tap water and river water, the recovery rate and RSD (n = 3) were calculated as 94.1~103% and 1.0~3.3, respectively, showing good recovery, reliable results, and outstanding stability. Therefore, the proposed colorimetric sensor array will have a great potential for the detection of phenols in the environment. Schematic presentation of a simple and sensitive colorimetric strategy based on the laccase-mimicking activity of Cu-modified UiO-type metal-organic framework (MOFs, Uio-67-Cu) to distinguish phenols with analogous structures.
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http://dx.doi.org/10.1007/s00604-021-04944-5DOI Listing
July 2021

METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis.

Front Med (Lausanne) 2021 6;8:607585. Epub 2021 Jul 6.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China.

Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the -methyladenosine (mA) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response the NF-κB signaling pathway.
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http://dx.doi.org/10.3389/fmed.2021.607585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290917PMC
July 2021

Simulation of portal/hepatic vein associated remnant liver ischemia/congestion by three-dimensional visualization technology based on preoperative CT scan.

Ann Transl Med 2021 May;9(9):756

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Remnant liver hypoperfusion is frequently observed after hepatectomy, and associated with a higher risk of postoperative complications and poorer survival. However, the development of remnant liver hypoperfusion was not fully understood.

Methods: We retrospectively analyzed patients who received hepatectomy and took contrast-enhanced computed tomography (CT) scans before, 1-week (POW1) and 4-week (POW4) after resection in our department from June 2017 to July 2019. We simulated and estimated the occurrence of portal-vein-related remnant liver ischemia (RLI) and hepatic-vein-related remnant liver congestion (RLC) after hepatectomy via three-dimensional visualization technology (3DVT) according to blood vessels ligated in the resection; then we analyzed association between the estimated RLI, RLC, and postoperative clinical outcomes.

Results: A total of 102 eligible patients were analyzed. Remnant liver hypoperfusion was observed in 47 (46%) patients in the POW1 CT scans and shrunk in the POW4 CT scans. RLC had better diagnostic significance than RLI in predicting remnant liver hypoperfusion [area under receiver operating characteristic (ROC) curve: 0.745 0.569, P=0.026]. Multivariate analysis showed that larger RLI [odds ratio (OR), 1.154; 95% confidence interval (CI), 1.075-1.240; P<0.001] was independent risk factor for post-hepatectomy liver failure (PHLF). Besides, larger RLC (OR, 1.114; 95% CI, 1.032-1.204; P=0.006) was independent risk factor for major postoperative complications.

Conclusions: Remnant liver hypoperfusion can be predicted during the preoperative surgical plan by 3DVT. Portal vein related RLI was associated with PHLF, and hepatic vein related RLC was associated with major postoperative complications. Preservation of the hepatic vein and complete removal of the perfusion territory of ligated vessels are essential procedures to reduce RLI/RLC and the risk of PHLF or other surgical complications.
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http://dx.doi.org/10.21037/atm-20-7920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246180PMC
May 2021

Safety but Limited Efficacy of Ensartinib in ROS1-Positive Non-small Cell Lung Cancer: A Single-arm, Multicenter Phase II study.

J Thorac Oncol 2021 Jul 12. Epub 2021 Jul 12.

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. Electronic address:

Introduction: Some Anaplastic lymphoma kinase (ALK) inhibitors with good inhibition of ROS1 in preclinical studies has been reported possibly beneficial in ROS1-positive non-small cell lung cancer (NSCLC). In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC.

Methods: The exploratory study was a phase II single-arm, multicenter design (NCT03608007). ROS1-positive NSCLC patients with a prior chemotherapy line number of ≤1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary endpoint was objective response rate (ORR) evaluated by investigator per Response Evaluation Criteria in Solid Tumors version 1.1.

Results: From June 2018 to July 2019, 59 patients were enrolled at 23 centers in China. At the time of data cutoff, the median follow-up was 19.8 months (range 0.8-22.5). The median ORR was 27.0% (95 % CI 13.8, 44.1) with 10 partial responses. Median duration of response (DoR) was 4.8 months (95% CI 1.8-10.8). The median progression-free survival (PFS) was 4.6 months (95% CI 4.0-6.4). The median overall survival (OS) was not estimable (95% CI 14.9-not estimable). Of 4 patients with brain metastases, intracranial disease control was reported in 3 (75.0%; 95% CI 19.4-99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. The most of TRAEs were grade 1-2, and incidence of grade ≥3 TRAEs was 25.4%.

Conclusions: Ensartinib had a moderset efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.
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http://dx.doi.org/10.1016/j.jtho.2021.06.023DOI Listing
July 2021

Role of the F-BAR Family Member PSTPIP2 in Autoinflammatory Diseases.

Front Immunol 2021 28;12:585412. Epub 2021 Jun 28.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.

Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) belongs to the Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain family. It exhibits lipid-binding, membrane deformation, and F-actin binding activity, suggesting broader roles at the membrane-cytoskeleton interface. PSTPIP2 is known to participate in macrophage activation, neutrophil migration, cytokine production, and osteoclast differentiation. In recent years, it has been observed to play important roles in innate immune diseases and autoinflammatory diseases (AIDs). Current research indicates that the protein tyrosine phosphatase PTP-PEST, Src homology domain-containing inositol 5'-phosphatase 1 (SHIP1), and C-terminal Src kinase (CSK) can bind to PSTPIP2 and inhibit the development of AIDs. However, the mechanisms underlying the function of PSTPIP2 have not been fully elucidated. This article reviews the research progress and mechanisms of PSTPIP2 in AIDs. PSTPIP2 also provides a new therapeutic target for the treatment of AIDs.
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http://dx.doi.org/10.3389/fimmu.2021.585412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273435PMC
June 2021

HMGB1 Translocation is Associated with Tumor-Associated Myeloid Cells and Involved in the Progression of Fibroblastic Sarcoma.

Pathol Oncol Res 2021 31;27:608582. Epub 2021 Mar 31.

Department of Pathology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.

The morphological variability and genetic complexity of fibroblastic sarcoma makes its diagnosis and treatment a challenge. High-mobility group box 1 protein (HMGB1), which functions as a DNA chaperone and a prototypical damage-associated molecular pattern, plays a paradoxical role in cancer. However, the expression pattern and role of HMGB1 in fibroblastic sarcomas is ill defined. By immunostaining of 95 tissue microarray cores of fibroblastic sarcomas, HMGB1 was found to be expressed in most tumor tissues. Nuclear HMGB1 translocation to cytoplasm was observed both in tumor cells and vascular endothelial cells. A visible number of tumor-associated myeloid cells including CD68 and CD163 macrophages and CD33 myeloid cells were also detected in most tumor tissues. HMGB1 translocation was not only associated with CD68, CD163, and CD33 density, but also with disease progression. These results imply that HMGB1, an important regulator of the tumor microenvironment, is associated with tumor-associated myeloid cells and involved in the progression of fibroblastic sarcomas; HMGB1 may serve as a promising prognostic biomarker and a potential therapeutic target for fibroblastic sarcoma.
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http://dx.doi.org/10.3389/pore.2021.608582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262203PMC
March 2021

Rev-erbα exacerbates hepatic steatosis in alcoholic liver diseases through regulating autophagy.

Cell Biosci 2021 Jul 10;11(1):129. Epub 2021 Jul 10.

School of Pharmacy, Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei, 230032, Anhui, China.

Background And Aims: Alcoholic fatty liver (AFL) is a liver disease caused by long-term excessive drinking and is characterized by hepatic steatosis. Understanding the regulatory mechanism of steatosis is essential for the treatment of AFL. Rev-erbα is a member of the Rev-erbs family of nuclear receptors, playing an important role in regulating lipid metabolism. However, its functional role in AFL and its underlying mechanism remains unclear.

Results: Rev-erbα was upregulated in the liver of EtOH-fed mice and EtOH-treated L-02 cells. Further, Rev-erbα activation exacerbates steatosis in L-02 cells. Inhibition/downexpression of Rev-erbα improved steatosis. Mechanistically, autophagy activity was inhibited in vivo and vitro. Interestingly, inhibition/downexpression of Rev-erbα enhanced autophagy. Furthermore, silencing of Rev-erbα up-regulated the nuclear expression of Bmal1. Autophagy activity was inhibited and steatosis was deteriorated after EtOH-treated L-02 cells were cotransfected with Rev-erbα shRNA and Bmal1 siRNA.

Conclusions: Rev-erbα induces liver steatosis, which promotes the progression of AFL. Our study reveals a novel steatosis regulatory mechanism in AFL and suggest that Rev-erbα might be a potential therapeutic target for AFL.
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http://dx.doi.org/10.1186/s13578-021-00622-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272374PMC
July 2021

Development and Validation of a Nomogram Based on Perioperative Factors to Predict Post-hepatectomy Liver Failure.

J Clin Transl Hepatol 2021 Jun 15;9(3):291-300. Epub 2021 Mar 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background And Aims: Post-hepatectomy liver failure (PHLF) is a severe complication and main cause of death in patients undergoing hepatectomy. The aim of this study was to build a predictive model of PHLF in patients undergoing hepatectomy.

Methods: We retrospectively analyzed patients undergoing hepatectomy at Zhongshan Hospital, Fudan University from July 2015 to June 2018, and randomly divided them into development and internal validation cohorts. External validation was performed in an independent cohort. Least absolute shrinkage and selection operator (commonly referred to as LASSO) logistic regression was applied to identify predictors of PHLF, and multivariate binary logistic regression analysis was performed to establish the predictive model, which was visualized with a nomogram.

Results: A total of 492 eligible patients were analyzed. LASSO and multivariate analysis identified three preoperative variables, total bilirubin (=0.001), international normalized ratio (<0.001) and platelet count (=0.004), and two intraoperative variables, extent of resection (=0.002) and blood loss (=0.004), as independent predictors of PHLF. The area under receiver operating characteristic curve (referred to as AUROC) of the predictive model was 0.838 and outperformed the model for end-stage liver disease score, albumin-bilirubin score and platelet-albumin-bilirubin score (AUROCs: 0.723, 0.695 and 0.663, respectively; <0.001 for all). The optimal cut-off value of the predictive model was 14.7. External validation showed the model could predict PHLF accurately and distinguish high-risk patients.

Conclusions: PHLF can be accurately predicted by this model in patients undergoing hepatectomy, which may significantly contribute to the postoperative care of these patients.
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http://dx.doi.org/10.14218/JCTH.2021.00013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237151PMC
June 2021

The Emerging Roles of Pericytes in Modulating Tumor Microenvironment.

Front Cell Dev Biol 2021 11;9:676342. Epub 2021 Jun 11.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Pericytes (PCs), known as mural cells, play an important blood vessel (BV) supporting role in regulating vascular stabilization, permeability and blood flow in microcirculation as well as blood brain barrier. In carcinogenesis, defective interaction between PCs and endothelial cells (ECs) contributes to the formation of leaky, chaotic and dysfunctional vasculature in tumors. However, recent works from other laboratories and our own demonstrate that the direct interaction between PCs and other stromal cells/cancer cells can modulate tumor microenvironment (TME) to favor cancer growth and progression, independent of its BV supporting role. Furthermore, accumulating evidence suggests that PCs have an immunomodulatory role. In the current review, we focus on recent advancement in understanding PC's regulatory role in the TME by communicating with ECs, immune cells, and tumor cells, and discuss how we can target PC's functions to re-model TME for an improved cancer treatment strategy.
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http://dx.doi.org/10.3389/fcell.2021.676342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232225PMC
June 2021

Delayed Discharge after Thoracic Surgery under the Guidance of ERAS Protocols.

Thorac Cardiovasc Surg 2021 Jun 27. Epub 2021 Jun 27.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, People's Republic of China.

Background:  Enhanced recovery after surgery (ERAS) protocols have been applied in thoracic surgery and are beneficial to patients. However, some issues about ERAS are still pending.

Methods:  A total of 1,654 patients who underwent thoracic surgery under the guidance of ERAS protocols were enrolled in this study. We set the length of postoperative stay (LOPS) as our key research indicator. Patients were divided into routine discharge group and delayed discharge group based on LOPS. Causes of delayed discharge were analyzed to improve management of postoperative recovery.

Results:  Male, old age, underlying disease (coronary artery disease, chronic kidney disease, old cerebral infarction, chronic obstructive pulmonary disease, and arrhythmia), intensive care unit (ICU) stay, type of insurance, and lower forced expiratory volume in one second (FEV1) are the independent impact factors causing delayed discharge. Increased nonchylous drainage (INCD) and prolonged air leakage were the two leading causes for delayed discharge.

Conclusion:  Patients should have personalized recovery goal under the same ERAS protocols. We should accept that patients in poor general condition have a prolonged LOPS. More stringent ICU stay indications should be developed to increase postoperative patients' ERAS protocols compliance. Further research on chest tube management will make a contribution to ERAS protocols.
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http://dx.doi.org/10.1055/s-0041-1727232DOI Listing
June 2021

Asperuloside ameliorates lipopolysaccharide-induced primary human periodontal ligament cell injury by decreasing TLR4 expression and NF-κB activation.

Arch Oral Biol 2021 Jun 16;129:105199. Epub 2021 Jun 16.

Department of Stomatology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.

Objective: The mechanism underlying lipopolysaccharide (LPS)-induced primary human periodontal ligament (PDLC) cell injury is unclear. In this study, we focused on the therapeutic function of asperuloside (ASP) on LPS-induced cell injury.

Design: The study enrolled 41 participants, including 18 healthy controls and 23 CP patients. Western blotting was used to measure the expression of Toll-like receptor 4 (TLR4), phosphorylated p65 (p-p65) and cyclin D1. Enzyme-linked immunosorbent assays (ELISAs) were utilized to evaluate the protein levels of proinflammatory factors interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor alpha (TNF-α). MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) staining were performed to investigate cell proliferation. Immunohistochemistry was used to detect TLR4 and p65 expression in gingival tissues.

Results And Conclusions: Asperuloside ameliorates lipopolysaccharide-induced PDLC cell injury by decreasing TLR4 expression and NF-κB activation, while this protective effect of ASP was reversed by TLR4 overexpression.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105199DOI Listing
June 2021

Intermediate volatile organic compounds emissions from vehicles under real world conditions.

Sci Total Environ 2021 Sep 15;788:147795. Epub 2021 May 15.

State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex, Shanghai Academy of Environmental Sciences, Shanghai 200233, China.

Real-world vehicle emission factors (EFs) for the total intermediate volatile organic compounds (total-IVOCs) and volatile organic compounds (VOCs) from mixed fleets of vehicles were quantified in the Yangtze tunnel in Shanghai. Relationships of EFs of IVOCs with fleet compositions and vehicle speed as well as secondary organic formation potentials (SOAFPs) from IVOCs and VOCs were studied. Multiple linear regression (MLR) was used to estimate EFs of total-IVOCs for gasoline and diesel vehicles. IVOCs were classified into unresolved complex mixtures (unspeciated cyclic compounds and branched alkanes (b-alkanes)) and speciated targets (11 n-alkanes and ten polycyclic aromatic hydrocarbons (PAHs)). The results showed that the average EF of total-IVOCs was 24.9 ± 7.8 mg/(km·veh), which was comparable to that of VOCs. Unspeciated cyclic compounds and b-alkanes dominated the main composition (~77% and ~19%), followed by n-alkanes (~4%) and PAHs (~1%). EFs of IVOCs showed a significant, positive relationship with diesel vehicle fractions (p < 0.05). EFs of IVOCs dropped notably with the decrease of the diesel vehicle fractions. SOAFP produced by the total organic compounds (IVOCs + VOCs) was 8.9 ± 2.5 mg/(km·veh), in which up to 86% of SOAFP was from IVOCs. Estimated EFs of total-IVOCs for gasoline vehicles and diesel vehicles were 15.3 and 219.8 mg/(km·veh) respectively. Our results demonstrate that IVOCs emitted from diesel vehicles are the main emission sources under real world conditions and significant contributions of IVOCs emissions to SOA formation is evident, which indicates the necessity of making control policies to reduce IVOCs emissions from vehicles.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147795DOI Listing
September 2021

Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.

Nat Biomed Eng 2021 Jun 15;5(6):586-599. Epub 2021 Jun 15.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai, China.

The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.
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http://dx.doi.org/10.1038/s41551-021-00746-5DOI Listing
June 2021

Alternative activation of macrophages by prostacyclin synthase ameliorates alcohol induced liver injury.

Lab Invest 2021 Jun 10. Epub 2021 Jun 10.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, 230032, China.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide. Macrophages exhibit different functional states and are classified as classically activated (M1) and alternatively activated (M2) macrophages. However, the mechanisms that govern M1/M2 polarization in chronic ALD remain to be elucidated. Prostacyclin (PGI) synthase (PTGIS) is an enzyme of the prostaglandin pathway which catalyzes the conversion of Prostaglandin H (PGH) to PGI. PTGIS has anti-inflammatory properties. However, the function of PTGIS in ALD has not yet been determined. In this study, we demonstrated that PTGIS was downregulated in ALD and forced PTGIS expression in vivo using recombinant adeno-associated viral vector-packed PTGIS overexpression plasmid, which alleviated the inflammatory response and suppressed the macrophage M1 phenotype in mice. Loss- and gain-of function-experiments demonstrated that forced PTGIS expression inhibited the macrophage switch to the M1 phenotype and promoted M2 polarization. Furthermore, we identified the genes regulated by PTGIS through RNA-sequencing (RNA-seq) analysis. Gene ontology and KEGG pathway analyses showed that PTGIS regulates many genes involved in the immune response and is enriched in the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signal transduction pathway, which plays an important role in regulating macrophage polarization. The proteins interacting with JAKs were predicted using the STRING database. The overlap between the RNA-seq and the STRING database was interleukin-6; this indicated that it was involved in macrophage polarization regulated by JAK/STAT signaling. We further explored the microRNAs that could regulate the expression of PTGIS through TargetScan. The results of luciferase assay illustrated that the expression of PTGIS was regulated by miR-140-3p.1. These results imply that PTGIS plays a pivotal role in ALD, partly by influencing macrophage polarization.
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http://dx.doi.org/10.1038/s41374-021-00531-7DOI Listing
June 2021

Wide-range lifetime-tunable and responsive ultralong organic phosphorescent multi-host/guest system.

Nat Commun 2021 Jun 10;12(1):3522. Epub 2021 Jun 10.

Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) & Xi'an Institute of Biomedical Materials and Engineering (IBME), Northwestern Polytechnical University, Xi'an, China.

The rational lifetime-tuning strategy of ultralong organic phosphorescence is extraordinarily important but seldom reported. Herein, a series of multi-host/guest ultralong organic phosphorescence materials with dynamic lifetime-tuning properties were reported. By doping a non-room-temperature phosphorescence emitter into various solid host matrices with continuously reduced triplet energy levels, a wide-range lifetime (from 3.9 ms gradually to 376.9 ms) phosphorescence with unchangeable afterglow colors were realized. Further studies revealed that the host matrices were employed to afford rigid environment and proper energy levels to generate and stabilize the long-live triplet excitons. Meanwhile, these multi-host/guest ultralong organic phosphorescence materials also exhibited excitation-dependent phosphorescence and temperature-controlled afterglow on/off switching properties, according to the virtue of various photophysical and thermal properties of the host matrices. This work provides a guiding strategy to realize lifetime-tuning ultralong organic phosphorescence with lifetime-order encoding characteristic towards widespread applications in time-resolved information displaying, higher-level security protection, and dynamic multi-dimensional anti-counterfeiting.
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http://dx.doi.org/10.1038/s41467-021-23742-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192513PMC
June 2021

The miR-455-3p/HDAC2 axis plays a pivotal role in the progression and reversal of liver fibrosis and is regulated by epigenetics.

FASEB J 2021 07;35(7):e21700

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.

Histone deacetylases (HDACs), especially HDAC2, play a role in alleviating liver fibrosis; however, the specific upstream regulation mechanism is unknown. Herein, TargetScan was used to predict the potential upstream targets of HDAC2, and the role of miR-455-3p was explored. The dual luciferase reporter assay showed that miR-455-3p binds to the 3' UTR of HDAC2 mRNA. Additionally, miR-455-3p was downregulated in the liver tissues of patients with cirrhosis and mice with liver fibrosis, as well as in primary HSCs isolated from fibrotic mouse livers and TGF-β-treated LX-2 cells. In contrast, it is highly expressed in the reversal stage of hepatic fibrosis and MDI-cultured LX-2 cells. Our functional analyses showed that miR-455-3p overexpression facilitated apoptosis and reduced the expression of pro-fibrotic markers and the proliferation of activated LX-2 cells. On the contrary, miR-455-3p inhibition converted inactivated LX-2 cells into activated, proliferative, fibrogenic cells. Interestingly, restoration of HDAC2 expression partially blocked the function of miR-455-3p. Downregulated miR-455-3p expression can be restored by DNA methyltransferases in activated LX-2 cells. Methylation-specific PCR, bisulfite sequencing PCR, and chromatin immunoprecipitation assays indicated that the methylation level of miR-455-3p promoter CpG islands was elevated in TGF-β-treated LX-2 cells and that miR-455-3p was downregulated in activated LX-2 cells by DNA hypermethylation, which is mediated by DNMT3b and DNMT1. In conclusion, miR-455-3p acts as a liver fibrosis suppressor by targeting HDAC2, and its deficiency further aggravates the reversal phase of fibrosis. Thus, the epigenetics mediated miR-455-3p/HDAC2 axis may serve as a novel potential therapeutic target for clinical treatment of hepatic fibrosis.
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http://dx.doi.org/10.1096/fj.202002319RRRDOI Listing
July 2021

Red blood cell distribution width predicts residual renal function decline in patients undergoing continuous ambulatory peritoneal dialysis.

Ther Apher Dial 2021 Jun 8. Epub 2021 Jun 8.

Department of Nephrology, Huizhou Municipal Central Hospital, Huizhou, China.

To investigate the relationship between red blood cell distribution width (RDW) and residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Seventy-seven CAPD patients were enrolled in this study. According to receiver operator characteristic (ROC) curve analysis, patients were divided into high RDW (RDW > 14.95%) and low RDW (RDW ≤ 14.95%) groups. The data of baseline clinical, biochemical parameters, comorbidities, medication status, peritoneal function, and dialysis adequacy were compared. Survival curves were calculated using Kaplan-Meier method. Cox regression model was employed to analyze risk factors of decline in RRF. The overall median survival time was 24 months, the median survival time of high RDW group (46 patients) and low RDW group (31 patients) were 24 and 12 months, respectively. Compared with the low RDW group, patients in the high RDW group were older, higher rate of decline RRF and white blood cells count as well as lower total Kt/V (all p < 0.05). Kaplan-Meier survival curves showed that the low RDW group had higher survival of RRF compared with the high RDW group (p < 0.001). Multivariate Cox regression analysis showed that high RDW was independent risk factor for decline of RRF(hazard ratio = 1.441, 95% confidence interval: 1.089-1.905, p = 0.01). Increased baseline RDW is associated with decline of RRF in CAPD patients and RDW can be stratified as a valuable indicator for the risk of RRF decline.
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http://dx.doi.org/10.1111/1744-9987.13698DOI Listing
June 2021

ZnCdS Hollow Spheres with a Highly Dispersed Ni Dopant for Boosting Photocatalytic Hydrogen Generation.

ACS Omega 2021 Jun 21;6(21):13544-13553. Epub 2021 May 21.

Hubei Key Laboratory of Catalysis and Materials Science, School of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan 430074, China.

Facilitating charge separation and increasing surface active sites have always been the goals of photocatalysis. Herein, we synthesized a Ni-doped ZnCdS hollow sphere photocatalyst with a facile one-step hydrothermal method. Energy-dispersive spectroscopy mapping showed the high dispersion of Ni ions in the ZnCdS hollow spheres. The experimental results confirmed that Ni doping reduced the band structure of the substrate, suppressed the recombination of photo-induced electrons and holes, and provided more reactive sites. Therefore, the photocatalytic activity had been greatly improved. As a consequence, the detected photocatalytic H evolution rate increased up to 33.81 mmol·h·g over an optimal Ni doping (5 wt %) of ZnCdS hollow spheres, which was 20.87-fold higher than that of pure CdS. Elemental mapping showed that the Zn element was mainly distributed in the outermost layer of the hollow spheres; this might be the critical factor that enabled Ni-doped Zn Cd S to maintain excellent stability.
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http://dx.doi.org/10.1021/acsomega.0c06038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173556PMC
June 2021

Dichlorvos poisoning caused chicken cerebrum tissue damage and related apoptosis-related gene changes.

Sci Total Environ 2021 Aug 18;783:147051. Epub 2021 Apr 18.

Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, PR China. Electronic address:

Dichlorvos (DDVP) is an organophosphorus compound with insecticidal effects. Organophosphorus pesticides can easily enter humans or animals through various channels, causing cerebrum nerve cell damage. The purpose of this research was to investigate whether acute dichlorvos poisoning can cause cerebrum neurotoxic injury and change the expression of apoptosis-related genes in broilers, further clarify the neurotoxic mechanism after acute dichlorvos exposure, and provide a research basis for prevention, treatment and gene drug screening in the later stage. In this experiment, healthy yellow-feathered broilers were randomly assigned to the control group, the low-dose group (1.13 mg/kg) and the high-dose group (10.2 mg/kg) for modelling observation, and detection was conducted based on H&E (haematoxylin and eosin) staining, transmission electron microscopy analysis of tissue sections, immunofluorescence techniques and real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that organophosphorus poisoning was accompanied by obvious neurological symptoms such as limb twitching and massive salivation. In addition, we observed that compared with the control group, the number of lysed nuclear neurons, deformed vascular sheaths, and glial cells and the expression of glial fibrillary acidic protein (GFAP) in the poisoned group of broilers increased significantly, and the increase was more obvious in the low-dose group. However, cell apoptosis and mitochondrial structure dissolution were most pronounced in the high-dose group. Moreover, the qRT-PCR results also revealed significant changes in the expression of apoptosis-related genes. The expression levels of ACC, LKB1 and GPAT increased significantly, while the expression of HMGR, PPARα, CPT1 and AMPKα1 decreased significantly. In summary, these results indicated that dichlorvos may cause the lysis of cerebrum nerve cell nuclei, completely destroy the structure of mitochondria, change the expression of related apoptotic genes, enhance cell apoptosis, and cause neurogenic damage to the cerebrum. These research results offer a theoretical foundation for the prevention and treatment of acute organophosphate toxicosis.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147051DOI Listing
August 2021

A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway.

Cancer Cell Int 2021 May 30;21(1):285. Epub 2021 May 30.

CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.

Background: Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity.

Methods: We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro.

Results: The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed.

Conclusion: The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.
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http://dx.doi.org/10.1186/s12935-021-01973-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165811PMC
May 2021

Component Parts of Bacteriophage Virions Accurately Defined by a Machine-Learning Approach Built on Evolutionary Features.

mSystems 2021 Jun 27;6(3):e0024221. Epub 2021 May 27.

Infection & Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Australia.

Antimicrobial resistance (AMR) continues to evolve as a major threat to human health, and new strategies are required for the treatment of AMR infections. Bacteriophages (phages) that kill bacterial pathogens are being identified for use in phage therapies, with the intention to apply these bactericidal viruses directly into the infection sites in bespoke phage cocktails. Despite the great unsampled phage diversity for this purpose, an issue hampering the roll out of phage therapy is the poor quality annotation of many of the phage genomes, particularly for those from infrequently sampled environmental sources. We developed a computational tool called STEP to use the "evolutionary features" that can be recognized in genome sequences of diverse phages. These features, when integrated into an ensemble framework, achieved a stable and robust prediction performance when benchmarked against other prediction tools using phages from diverse sources. Validation of the prediction accuracy of STEP was conducted with high-resolution mass spectrometry analysis of two novel phages, isolated from a watercourse in the Southern Hemisphere. STEP provides a robust computational approach to distinguish specific and universal features in phages to improve the quality of phage cocktails and is available for use at http://step3.erc.monash.edu/. In response to the global problem of antimicrobial resistance, there are moves to use bacteriophages (phages) as therapeutic agents. Selecting which phages will be effective therapeutics relies on interpreting features contributing to shelf-life and applicability to diagnosed infections. However, the protein components of the phage virions that dictate these properties vary so much in sequence that best estimates suggest failure to recognize up to 90% of them. We have utilized this diversity in evolutionary features as an advantage, to apply machine learning for prediction accuracy for diverse components in phage virions. We benchmark this new tool showing the accurate recognition and evaluation of phage component parts using genome sequence data of phages from undersampled environments, where the richest diversity of phage still lies.
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http://dx.doi.org/10.1128/mSystems.00242-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269216PMC
June 2021

Increase of Portal Vein Pressure Gradient After Hepatectomy Predicts Post-operative Liver Dysfunction.

Surg Innov 2021 May 15:15533506211018620. Epub 2021 May 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Zhongshan Hospital, 92323Fudan University, Shanghai, China.

. Post-hepatectomy liver failure (PHLF) is an important cause of mortality and morbidity. Whether Child-Pugh A patients with varying degrees of cirrhosis are good candidates for hepatectomy is disputed. The purpose of this study was to analyze the impact of portal venous pressure gradient (PVPG) variation during surgery on PHLF. . PVPG, the pressure gradient between the portal vein and central vein, was measured in consecutive patients before and after liver resection. The optimal cutoff of PVPG to predict PHLF was determined by receiver operating characteristic curve analysis. Risk factors for PHLF were subjected to univariate and multivariable analysis. . Sixty Child-Pugh A patients were recruited. The mean PVPG was increased from 5.17 ± 4.78 mm of mercury (mmHg) to 6.37 ± 4.44 mmHg after liver resection. The optimal cutoff value of PVPG increments to predict PHLF was 1.5 mmHg. Multivariable analysis showed prothrombin time (PT), post-hepatectomy PVPG increments of 1.5 mmHg or greater, and resected liver segments of 3 or more to be independent predictors of PHLF. . Acute PVPG increase after hepatectomy is associated with a higher risk of PHLF in Child-Pugh A patients.
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http://dx.doi.org/10.1177/15533506211018620DOI Listing
May 2021
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