Publications by authors named "Yaling Li"

82 Publications

The total synthesis of -strempeliopine palladium-catalyzed decarboxylative asymmetric allylic alkylation.

Chem Commun (Camb) 2022 Jan 27;58(9):1402-1405. Epub 2022 Jan 27.

Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

In the work reported herein, the concise and enantioselective total synthesis of the alkaloid (-)-strempeliopine was developed. This synthetic strategy featured the palladium-catalyzed decarboxylative asymmetric allylic alkylation of -benzoyl lactam to set up the absolute configuration at the C20 position, a highly diastereoselective one-pot Bischler-Napieralski/lactamization and iminium reduction sequence for the construction of the pentacyclic core structure, and the late-stage dearomative addition of indole, leading to the otherwise difficult-to-achieve hexacyclic indoline framework with complete control of four neighbouring stereocenters.
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http://dx.doi.org/10.1039/d1cc06278fDOI Listing
January 2022

Resting-State Functional Magnetic Resonance Imaging Reveals Overactivation of the Habitual Control Brain System in Tobacco Dependence.

Neuropsychiatr Dis Treat 2021 19;17:3753-3768. Epub 2021 Dec 19.

Department of Geriatrics, Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong Province, People's Republic of China.

Introduction: We studied the regulatory mechanism of the habitual brain network in tobacco dependence to provide a theoretical basis for the regulation and cessation of tobacco dependence.

Methods: We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the Fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity (FC) of the habitual brain network in tobacco-dependent subjects and to evaluate the relationship between the FC level and tobacco selection preference behavior. In total, 29 male tobacco-dependent participants and 28 male nonsmoking participants were recruited. rs-fMRI was used to collect blood oxygen level-dependent signals of the participants in the resting and awake states. After rs-fMRI, all subjects completed cigarette/coin selection tasks (task 1 and task 2).

Results: Compared with the control group, the tobacco dependence group showed increased fractional amplitude values of fALFF in the left posterior cingulate cortex and right parahippocampus. FC in the tobacco-dependent group was increased in the right inferior temporal gyrus, left middle frontal gyrus, left cingulated gyrus, and bilateral superior frontal gyrus, compared with that in the control group. Moreover, the preference selection behavior was associated with the enhancement of FC about parts of the brain regions in the habitual brain network of the tobacco-dependent participants. Thus, habitual network activity was significantly enhanced in tobacco-dependent participants in the resting state. Moreover, a positive correlation was found between the cigarette selection preference of the smokers and certain brain regions related to the habitual network.

Discussion: This suggests that increased activity of the habitual brain network may be essential in the development of tobacco-dependent behavior.
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http://dx.doi.org/10.2147/NDT.S334403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8703225PMC
December 2021

Wild bird-origin H3N8 avian influenza virus exhibit well adaptation in mammalian host.

J Infect 2021 Dec 23. Epub 2021 Dec 23.

College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang 832000, China; Key Laboratory of Control and Prevention of Animal Disease, Xinjiang Production and Construction Corps, Shihezi 832000, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.12.014DOI Listing
December 2021

The Impact of Age Difference on the Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

Front Immunol 2021 6;12:758294. Epub 2021 Dec 6.

Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Objective: This meta-analysis compared the efficacy and safety of five kinds of COVID-19 vaccines in different age groups (young adults and older adults), aiming to analyze the difference of adverse events (AEs) rate and virus geometric mean titer (GMT) values between young and older people, in order to find a specific trend, and explore the causes of this trend through meta-analysis.

Method: Meta-analysis was used to analyze the five eligible articles. The modified Jadad scoring scale was used to evaluate the quality of eligible literature with a scoring system of 1 to 7. The primary endpoint of the effectiveness index was GMT. The primary endpoints of the safety index were the incidence of local AEs and systemic AEs. Stata 12.0 software was used for meta-analysis. Revman 5.0 software was used to map the risk of publication bias, and Egger's test was used to analyze publication bias.

Results: The GMT values of young adults were higher than older adults (SMD = 1.40, 95% CI (0.79, 2.02), P<0.01). There was a higher incidence of local and systemic AEs in young people than in the elderly (OR = 1.10, 95% CI (1.08, 1.12), P<0.01; OR = 1.18, 95% CI (1.14, 1.22), P<0.01).

Conclusion: The immune effect of young people after being vaccinated with COVID-19 vaccines was better than that of the elderly, but the safety was worse than that of old people, the most common AEs were fever, rash, and local muscle pain, which were tolerable for young people. As the AEs of the elderly were lower, they can also be vaccinated safely; the reason for the low level of GMT in the elderly was related to Immunosenescence. The vaccine tolerance of people of different ages needs to be studied continuously.
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http://dx.doi.org/10.3389/fimmu.2021.758294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8685545PMC
January 2022

Uncovering a Key Role of ETS1 on Vascular Abnormality in Glioblastoma.

Pathol Oncol Res 2021 19;27:1609997. Epub 2021 Nov 19.

Hunan University of Medicine, Huaihua, China.

Glioblastoma (GBM) is the most aggressive type of brain tumor. Microvascular proliferation and abnormal vasculature are the hallmarks of the GBM, aggravating disease progression and increasing patient morbidity. Here, we uncovered a key role of ETS1 on vascular abnormality in glioblastoma. ETS1 was upregulated in endothelial cells from human tumors compared to endothelial cells from paired control brain tissue. Knockdown of Ets1 in mouse brain endothelial cells inhibited cell migration and proliferation, and suppressed expression of genes associated with vascular abnormality in GBM. ETS1 upregulation in tumor ECs was dependent on TGFβ signaling, and targeting TGFβ signaling by inhibitor decreased tumor angiogenesis and vascular abnormality in CT-2A glioma model. Our results identified ETS1 as a key factor regulating tumor angiogenesis, and suggested that TGFβ inhibition may suppress the vascular abnormality driven by ETS1.
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http://dx.doi.org/10.3389/pore.2021.1609997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8641556PMC
November 2021

Association between high-density lipoprotein cholesterol and apolipoprotein A-I and severe acute pancreatitis: a case-control study.

Eur J Gastroenterol Hepatol 2021 12;33(12):1517-1523

Department of Gastroenterology.

Background: Evidence is limited concerning the association between serum concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (APO A-I) and severe acute pancreatitis (SAP). This study was designed to explore whether HDL-C and APO A-I were independently correlated to SAP after adjusting for covariates.

Methods: There were 1127 patients with acute pancreatitis who were recruited from a tertiary teaching hospital in Wenzhou from 1 January 2018 to 30 April 2020. The independent variables were baseline levels of HDL-C, and APO A-I collected within 24 h after admission. The dependent variable was the occurrence of SAP during hospitalization. Univariate and multivariate binary logistic regression were conducted to analyze the relationship between HDL-C and APO A-I and SAP. The receiver operating characteristic curve was applied to analyze the prediction power of lipid parameters and C-reactive protein for SAP.

Results: The incidence of SAP was 11.5% among the 678 patients included in the final analysis. The serum levels of APO A-I and HDL-C were negatively related to SAP after adjusting for confounders with an odds ratio of 0.24 [95% confidence interval (CI): 0.06-0.95] and 0.16 (95% CI, 0.04-0.56), respectively. APO A-I (area under the curve = 0.69; 95% CI, 0.63-0.76) and HDL-C (area under the curve = 0.72; 95% CI, 0.66-0.79) showed higher predictive value for SAP compared with other lipid parameters.

Conclusions: Decreased serum concentrations of HDL-C and APO A-I are associated with SAP after adjusting for covariates.
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http://dx.doi.org/10.1097/MEG.0000000000002095DOI Listing
December 2021

Incidence and Risk of Hypertension in Cancer Patients Treated With Atezolizumab and Bevacizumab: A Systematic Review and Meta-Analysis.

Front Oncol 2021 12;11:726008. Epub 2021 Oct 12.

Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Purpose: This study aims to inform previous clinical assessments to better understand the total risk of hypertension with atezolizumab and bevacizumab (hereafter referred to as "A-B") in cancer patients, and reduce future incidence of hypertension-related cardiovascular complications.

Methods: Databases, including PubMed, Embase, Cochrane, and Web of Science were searched to identify relevant studies, which were retrieved from inception to March 6, 2021. Studies focused on cancer patients treated with A-B that provided data on hypertension were included. Statistical analyses were conducted to calculate hypertension incidence and relative risk (RR) with a random-effects or fixed-effects model, hinging on heterogeneity status.

Results: Ten studies including 2106 patients with renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), ovarian cancer, anal cancer, neuroendocrine tumors (NETs), and cervical cancer were selected for this meta-analysis. For patients treated with A-B, the all-grade and high-grade (grade 3) hypertension incidence were 31.1% (95% CI: 25.5-37.3) and 14.1% (95% CI: 10.9-18.1), respectively. No significant difference was observed in all-grade hypertension incidence between RCC and a non-RCC patients (32.9% [95% CI: 25.3-42.6] 29.2% [95% CI: 19.7-39.6)]). However, the number of high-grade hypertension incidence in RCC patients (9.4% [95% CI: 4.1-21.3]) was lower than that of non-RCC patients (15.6% [95% CI: 12.8-19.1]). RCC or HCC patients who received the A-B treatment were associated with significantly increased risk of all-grade hypertension with a RR of 7.22 (95% CI: 3.3-15.7; = 0.6) compared with patients treated with atezolizumab.

Conclusions: Cancer Patients treated with atezolizumab and bevacizumab have a significantly increased risk of hypertension. Sufficient monitoring is highly recommended to prevent the consequences of treatment-induced hypertension and other cardiovascular complications.
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http://dx.doi.org/10.3389/fonc.2021.726008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546244PMC
October 2021

SsATG8 and SsNBR1 mediated-autophagy is required for fungal development, proteasomal stress response and virulence in Sclerotinia sclerotiorum.

Fungal Genet Biol 2021 12 26;157:103632. Epub 2021 Oct 26.

Fujian University Key Laboratory for Plant-Microbe Interaction, College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China; Haixia Institute of Science and Technology, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China. Electronic address:

Autophagy plays vital roles in the interaction between the necrotrophic fungal pathogen Sclerotinia sclerotiorum and its hosts. However, so far, only little is known about the impacts of autophagy machinery in S. sclerotiorum per se on the fungal morphogenesis and pathogenesis. Here, through functional genomic approaches, we showed that SsATG8, one of the core components of the autophagy machinery, and its interactor SsNBR1, an autophagy cargo receptor, are important for vegetative growth, sclerotial formation, oxalic acid (OA) production, compound appressoria development, and virulence of S. sclerotiorum. Complementation assays with chimeric fusion constructs revealed that both LDS [AIM (ATG8 interacting motif) / LIR (LC3-interacting region) docking site] and UDS [UIM (ubiquitin-interacting motif) docking site] sites of the SsATG8 are required for its functions in autophagy and pathogenesis. Importantly, ΔSsatg8 and ΔSsnbr1 mutants showed enhanced sensitivity to the exogenous treatment with the proteasome inhibitors bortezomib and carfilzomib, and ΔSsnbr1 mutant had decreased expression of SsATG8 under the proteasomal stress conditions, suggesting that a cross-talk exists between ubiquitin-proteasome and selective autophagy pathways, which enables downstream protein degradation to proceed properly during diverse biological processes. Collectively, our data indicate that SsATG8- and SsNBR1-mediated autophagy is crucial for S. sclerotiorum development, proteasomal stress response and virulence.
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http://dx.doi.org/10.1016/j.fgb.2021.103632DOI Listing
December 2021

Using Immune-Related lncRNA Signature for Prognosis and Response to Immunotherapy in Cutaneous Melanoma.

Int J Gen Med 2021 8;14:6463-6475. Epub 2021 Oct 8.

College of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, People's Republic of China.

Background: Cutaneous melanoma is a highly malignant skin tumor, and most patients have a poor prognosis. In recent years, immunotherapy has assumed an important role in the treatment of advanced cutaneous melanoma, but only a small percentage of patients benefit from immunotherapy. A growing number of studies have demonstrated that the prognosis of patients with cutaneous melanoma is closely related to long non-coding RNA and the tumor immune microenvironment.

Methods: We downloaded RNA expression data and immune-related gene lists of cutaneous melanoma patients separately from The Cancer Genome Atlas database and ImmPort website and identified immune-related lncRNAs by co-expression analysis. The prognostic model was constructed by applying least absolute shrinkage and selection operator regression, and all patients were classified into high- and low-risk groups according to the risk score of the model. We evaluated the differences between the two groups in terms of survival outcomes, immune infiltration, pathway enrichment, chemotherapeutic drug sensitivity and immune checkpoint gene expression to verify the impact of lncRNA signature on clinical prognosis and immunotherapy efficacy.

Results: By correlation analysis and LASSO regression analysis, we constructed an immune-related lncRNA prognostic model based on five lncRNA: HLA-DQB1-AS1, MIR205HG, RP11-643G5.6, USP30-AS1 and RP11-415F23.4. Based on this model, we plotted Kaplan-Meier survival curves and time-dependent ROC curves and analyzed its ability as an independent prognostic factor for cutaneous melanoma in combination with clinicopathological features. The results showed that these lncRNA signature was an independent prognostic factor of cutaneous melanoma with favorable prognostic ability. Our results also show a higher degree of immune infiltration, higher expression of immune checkpoint-associated genes, and better outcome of immunotherapy in the low-risk group of the lncRNA signature.

Conclusion: The 5 immune-related lncRNA signatures constructed in our study can predict the prognosis of cutaneous melanoma and contribute to the selection of immunotherapy.
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http://dx.doi.org/10.2147/IJGM.S335266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518697PMC
October 2021

Development and Validation of a Combined Glycolysis and Immune Prognostic Model for Melanoma.

Front Immunol 2021 1;12:711145. Epub 2021 Oct 1.

Department of Dermatology, The First Hospital of China Medical University and National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China.

Background: Glycolytic effects and immune microenvironments play important roles in the development of melanoma. However, reliable biomarkers for prognostic prediction of melanoma as based on glycolysis and immune status remain to be identified.

Methods: Glycolysis-related genes (GRGs) were obtained from the Molecular Signatures database and immune-related genes (IRGs) were downloaded from the ImmPort dataset. Prognostic GRGs and IRGs in the TCGA (The Cancer Genome Atlas) and GSE65904 datasets were identified. Least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression were used for model construction. Glycolysis expression profiles and the infiltration of immune cells were analyzed and compared. Finally, experiments were performed to assess the expression and function of these CIGI genes.

Results: Four prognostic glycolysis- and immune-related signatures ( and ) were identified for use in constructing a comprehensive glycolysis and immune (CIGI) model. CIGI proved to be a stable, predictive method as determined from different datasets and subgroups of patients and served as an independent prognostic factor for melanoma patients. In addition, patients in the high-CIGI group showed increased levels of glycolytic gene expressions and exhibited immune-suppressive features. Finally, and may function as tumor suppressor genes, while and may function as oncogenes in melanoma as revealed from results of experiments.

Conclusion: In this report we present our findings on the development and validation of a novel prognostic classifier for use in patients with melanoma as based on glycolysis and immune expression profiles.
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http://dx.doi.org/10.3389/fimmu.2021.711145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517401PMC
December 2021

Second-victim experience and support among nurses in mainland China.

J Nurs Manag 2022 Jan 29;30(1):260-267. Epub 2021 Oct 29.

Operating room, Guizhou Medical University school of Stomatology, Guiyang, China.

Aims: To investigate the experience and support of nurses as second victims in adverse events and explore factors.

Background: Adverse events have significant negative influences on healthcare professionals. However, there is still a lack of research on the impacts of individual and event factors.

Methods: A cross-sectional survey via a self-report electronic questionnaire was sent to approximately 6400 nurses from six tertiary comprehensive hospitals in mainland China. The socio-demographic, adverse event-related information and second-victim experience and support questionnaires were used.

Results: Approximately 2897 (45.26%) of nurses were involved in at least one adverse event that mainly caused psychological distress. Male nurses, Grade I adverse events, public reports and discussions of adverse events were related to the second-victim reaction. Discussing with a respected colleague was the most strongly desired form of support.

Conclusions: Chinese nurses have reported a high prevalence of psychological reactions. Follow-up studies must consider other potential factors.

Implications For Nursing Management: Nursing managers should consider the factors that affect second victims and provide support based on the expectations of nurses. Psychological first-aid and immediate and mid- to long-term support strategies should be provided to help the second victim alleviate distress.
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http://dx.doi.org/10.1111/jonm.13490DOI Listing
January 2022

Mastery of type 2 diabetes prevention and treatment knowledge by general practitioners in Shanghai: a cross-sectional study.

BMC Fam Pract 2021 09 17;22(1):189. Epub 2021 Sep 17.

Shanggang Community Healthcare Center of Pudong New Area, Shanghai, China.

Background: To study the competency of general practitioners (GPs) in Shanghai, China on prevention and management of type 2 diabetes, also understand factors that may prohibit it.

Methods: A survey questionnaire with 25 questions was designed based on 2013 Chinese Type 2 Diabetes Prevention Guidelines and Chinese Type 2 Diabetes Prevention Guidelines (Grassroots Edition) and conducted among 789 GPs who work at 54 community healthcare centers (CHCs) within 16 districts at Shanghai, China. Excel 2016 and SPSS 24.0 were used for data analysis, and a difference of P < 0.05 was considered to be statistically significant.

Results: The GPs did poorly on three aspect of diabetes prevention and treatment: (1) treatment goals in elderly patients, (2) screening methods for high-risk population, and (3) aspirin contraindications. The statistical analysis data showed that GPs who finished standardized training had correct answer on 13.58 ± 3.31 questions out of total 25, with mean accuracy rate of 54.32%. Except the questions for high-risk population screening method and the diagnostic criteria for type 2 diabetes, there was no difference in the accuracy of other questions between GPs with or without standardized training (P < 0.05). However, sex, educational level, and subspecialty experience are affective factors on their competency in type 2 diabetes prevention and treatment knowledge.

Conclusion: The results indicated that communities should strengthen the training of GPs in diabetes management and bidirectional referral. Frequent continuing education and skills training should be provided among GPs at CHCs to ensure their competency of type 2 diabetes prevention and treatment knowledge after obtaining their GP license disregard of their standardized training. In addition, attention should be paid to GPs who had lower education background or non-clinical subspecialty experience to strengthen their clinical knowledge of type 2 diabetes.
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http://dx.doi.org/10.1186/s12875-021-01538-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447626PMC
September 2021

LncRNA BASP1-AS1 interacts with YBX1 to regulate Notch transcription and drives the malignancy of melanoma.

Cancer Sci 2021 Nov 29;112(11):4526-4542. Epub 2021 Sep 29.

Department of Dermatology, The First Hospital of China Medical University and National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China.

Melanoma is a fatal skin malignant tumor with a poor prognosis. We found that long noncoding RNA BASP1-AS1 is essential for the development and prognosis of melanoma. The methylation, RNA sequencing, copy number variation, mutation data, and sample follow-up information of melanoma from The Cancer Genome Atlas (TCGA) were analyzed using weighted gene co-expression network analysis and 366 samples common to the three omics were selected for multigroup clustering analysis. A four-gene prognostic model (BASP1-AS1, LOC100506098, ARHGAP27P1, and LINC01532) was constructed in the TCGA cohort and validated using the GSE65904 series. The expression of BASP1-AS1 was upregulated in melanoma tissues and various melanoma cell lines. Functionally, the ectopic expression of BASP1-AS1 promoted cell proliferation, migration, and invasion in both A375 and SK-MEL-2 cells. Mechanically, BASP1-AS1 interacted with YBX1 and recruited it to the promoter of NOTCH3, initiating its transcription process. The activation of the Notch signaling then resulted in the transcription of multiple oncogenes, including c-MYC, PCNA, and CDK4, which contributed to melanoma progression. Thus, BASP1-AS1 could act as a potential biomarker for cutaneous malignant melanoma.
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http://dx.doi.org/10.1111/cas.15140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586662PMC
November 2021

Boosted polysulfides regulation by iron carbide nanoparticles-embedded porous biomass-derived carbon toward superior lithium-sulfur batteries.

J Colloid Interface Sci 2022 Jan 10;605:129-137. Epub 2021 Jul 10.

CAS Key Laboratory of Green Process and Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China; Center of Materials Science and Optoelectronics Engineering, School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China; Chemistry and Chemical Engineering Guangdong Laboratory, Shantou 515031, China. Electronic address:

Lithium-sulfur (Li-S) batteries are greatly expected to be the favored alternatives in the next-generation energy-storage technologies due to their exceptional advantages. However, the shuttle effect and sluggish reaction kinetics of polysulfides largely hamper the practical success of Li-S batteries. Herein, a unique iron carbide (FeC) nanoparticles-embedded porous biomass-derived carbon (FeC-PBC) is reported as the excellent immobilizer and promoter for polysulfides regulation. Such a distinctive composite strongly couples the vast active sites of FeC nanoparticles and the conductive network of porous biomass-derived carbon. Therefore, FeC-PBC is endowed with outstanding adsorptivity and catalytic effect toward inhibiting the shuttle effect and facilitating the redox kinetics of polysulfides, demonstrated by the detailed experimental demonstrations and theoretical calculation. With these synergistic effects, the FeC-PBC/S electrode embraces a superb capacity retention of 82.7% at 2C over 500 cycles and an excellent areal capacity of 4.81 mAh cm under the high-sulfur loading of 5.2 mg cm. This work will inspire the design of advanced hosts based on biomass materials for polysulfides regulation in pursuing the superior Li-S batteries.
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http://dx.doi.org/10.1016/j.jcis.2021.07.044DOI Listing
January 2022

Efficacy and Safety of Camrelizumab Monotherapy and Combination Therapy for Cancers: A Systematic Review and Meta-Analysis.

Front Oncol 2021 25;11:695512. Epub 2021 Jun 25.

Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, China.

Objective: This meta-analysis compared the safety and efficacy of camrelizumab monotherapy and combination therapy, aiming to provide a reference for the clinical combined use of camrelizumab in the treatment of cancers and also provide a reference for the development of subsequent indications of camrelizumab.

Methods: Meta-analysis was used to analyze the four eligible literatures. Primary endpoints of effectiveness index were objective response rate (ORR), progression-free survival (PFS), control rate (CR). Primary endpoint of safety index was rating of severity of adverse drug reactions (grades 1-5).

Results: The ORR, PFS, and CR values of combined treatment with camrelizumab was better than alone treatment, camrelizumab alone was better than chemotherapy (RR = 0.45; 95% CI, 0.30-0.67; P < 0.001; RR = 1.63; 95% CI, 1.25-2.13; P < 0.001; RR = 0.73; 95% CI, 0.52-1.02; P<0.001). When grade > 2, the incidence rate of combined treatment and chemotherapy are higher than monotherapy (RR = 0.66; 95% CI, 0.51-0.86; P<0.001). In any grade, the safety of camrelizumab combination therapy was better than that of monotherapy, the safety of chemotherapy was better than camrelizumab plus chemotherapy.

Conclusion: In terms of effectiveness, the combination of camrelizumab is better than monotherapy, and monotherapy is better than chemotherapy. In terms of safety, when the grade > 2, single use is better than combination therapy and chemotherapy. In any grade of adverse event, the safety of combined use of camrelizumab is better than that of single use, and the safety of chemotherapy is better than the combined use of camrelizumab plus chemotherapy.
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http://dx.doi.org/10.3389/fonc.2021.695512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268013PMC
June 2021

Incidence and influencing factors of post-intensive care cognitive impairment.

Intensive Crit Care Nurs 2021 Dec 7;67:103106. Epub 2021 Jul 7.

School of Nursing, Lanzhou University, Lanzhou, Gansu Province 730000, China; Department of Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, Gansu Province 730000, China. Electronic address:

Objective: To evaluate the incidence and risks factors of short-term post-intensive care (ICU) cognitive impairment.

Design: Prospective, observational study.

Setting: Closed university-affiliated intensive care unit.

Patients: We enrolled consecutive patients >18 yrs of age expected to be in intensive care unit for ≥24 hours.

Interventions: None.

Measurements And Main Results: The score of Montreal Cognitive Assessment (MoCA) less than 26 was defined as cognitive impairment at hospital discharge and short-term post-ICU cognitive impairment was diagnosed in 185 of 409 assessed patients (45.2%). According to univariate analysis, age, years of education, occupation, past medical history, main ICU diagnosis, Acute Physiology and Chronic Evaluation Scoring System (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, Charlson comorbidity index, ICU length-of-stay (LOS), total hospital LOS, sedation, vasoactive agents, muscle relaxants, mechanical ventilation and duration of mechanical ventilation, constraints, early active mobilisation, hypoxemia, frequency and severity of delirium, blood pressure, rescue experience, and infection were significant predictors of post-ICU cognitive impairment. Multivariate analysis results showed that the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors.

Conclusions: Incidence of post-ICU cognitive impairment is at a high level, which is similar to former researches' results; the frequency and severity of delirium, and advanced age were risk factors of post-ICU cognitive impairment; high years of education and early active mobilisation were protective factors of post-ICU cognitive impairment.
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http://dx.doi.org/10.1016/j.iccn.2021.103106DOI Listing
December 2021

Gastrodin extends the lifespan and protects against neurodegeneration in the Drosophila PINK1 model of Parkinson's disease.

Food Funct 2021 Sep 7;12(17):7816-7824. Epub 2021 Jul 7.

Provincial-Level Key Laboratory for Molecular Medicine of Major Diseases and The Prevention and Treatment with Traditional Chinese Medicine Research in Gansu Colleges and University, Gansu University of Chinese Medicine, Lanzhou 730000, China.

Gastrodin is the main bioactive ingredient of a famous Chinese herb Rhizoma Gastrodiae. Many studies have reported that gastrodin has antioxidative and neuroprotective effects, although its effect on longevity and the mechanism of neuroprotection have not been well studied. Here, we use Drosophila melanogaster as a model to investigate the longevity and neuroprotective effects of gastrodin. Gastrodin significantly extended the lifespan, increased the climbing ability, enhanced the resistance to oxidative stress, increased the enzyme activities of superoxide dismutase (SOD) and catalase (CAT), and promoted the expression of anti-oxidative genes in old flies. The food intake, reproduction and starvation resistance were not affected in flies treated with gastrodin. Moreover, gastrodin delayed the onset of Parkinson-like phenotypes in Pink1 mutant flies, including the prolongation of the lifespan, rescue of the climbing ability, rescue of the progressive loss of a cluster of dopaminergic neurons in the protocerebral posterial lateral 1 region, and increase of the dopamine content in the brain. Gastrodin did not ameliorate the tau-induced neurobehavioral deficits in the fly AD model of taupathy. Together, these results indicate that gastrodin could prolong the lifespan by regulating the antioxidant ability, and protect against neurodegeneration in the Pink1 model of PD. This suggests that gastrodin can be considered as an ideal therapeutic candidate for drug development towards anti-aging.
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http://dx.doi.org/10.1039/d1fo00847aDOI Listing
September 2021

Constructe a novel 5 hypoxia genes signature for cervical cancer.

Cancer Cell Int 2021 Jul 3;21(1):345. Epub 2021 Jul 3.

Department of Dermatology, The First Hospital of China Medical University and National Joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, 110001, China.

Background: Hypoxia, which affects the development, metastasis and prognosis of cancer, represents a key feature of cancer. This study describe a hypoxia risk factor model, with predicting the prognosis of cervical cancer.

Methods: Based on hypoxia pathway related genes, we divided cervical cancer samples into high and low expression groups. A cox analysis was then performed. Genes from these cervical cancer samples showing a significant impact on OS were selected for cluster analysis to obtain two subtypes. The TPM dataset of TCGA was divided into training and validation sets. For the training set, a lasso analysis was conducted as based on cox analysis of meaningful genes and a risk factor model was constructed. The constructed model was verified in internal and external data sets. Finally, RT-PCR, immunohistochemistry were used to detect the expression of relative genes or proteins and functional assays were used to evaluate the biological function of signature genes.

Results: Two molecular subtypes were obtained, Cluster2 vs Cluster1.These subtypes were obtained by clustering with a total of 149 DEGs (Differential expressed genes) being in line with this standard, of which 27 were up-regulated and 122 were down-regulated. The five genes with lambda = 0.0571 were selected to construct the model, the RiskScore = AK4*0.042 + HK2*0.021 + P4HA1*0.22 + TGFBI*0.1 + VEGFA*0.077. Further, in order to verify the signature, we used TCGA-test and GSE44001 chip datasets to test, and finally got a good risk prediction effect in those datasets. Moreover, the result of RT-PCR and immunohistochemistry demonstrated that AK4, HK2, P4HA1, TGFBI and VEGFA were all highly expressed in these cervical cancer tissue samples. The functional study shown that expression of AK4, HK2, P4HA1, TGFBI and VEGFA can regulate the proliferation, migration, and invasion ability of cervical cancer cells in vitro.

Conclusions: In summary, we developed a 5-gene signature prognostic hierarchical system based on the hypoxic pathway of cervical cancer, which is independent of clinical characteristics. And also conducted experimental verifications on these signature gene. Therefore, we propose that use of this classifier as a molecular diagnostic test can provide an effective means for evaluating the prognostic risk of cervical cancer patients, and provide potential targets for the treatment of cervical cancer patients.
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http://dx.doi.org/10.1186/s12935-021-02050-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254931PMC
July 2021

Machine Learning for the Prediction of Lymph Nodes Micrometastasis in Patients with Non-Small Cell Lung Cancer: A Comparative Analysis of Two Practical Prediction Models for Gross Target Volume Delineation.

Cancer Manag Res 2021 17;13:4811-4820. Epub 2021 Jun 17.

Department of Intensive Care Unit, Wuhan No. 1 Hospital, Wuhan, 430022, People's Republic of China.

Purpose: The lymph node gross target volume (GTV) delineation in patients with non-small cell lung cancer (NSCLC) is crucial for prognosis. This study aimed to develop a predictive model that can be used to differentiate between lymph nodes micrometastasis (LNM) and non-lymph nodes micrometastasis (non-LNM).

Patients And Methods: A retrospective study involving 1524 patients diagnosed with NSCLC was collected in the First Hospital of Wuhan between January 1, 2017, and April 1, 2020. Duplicated and useless variables were excluded, and 16 candidate variables were selected for further analysis. The random forest (RF) algorithm and generalized linear (GL) algorithm were used to screen out the variables that greatly affected the LNM prediction, respectively. The area under the curve (AUC) was compared between the RF model and GL model.

Results: The RF model revealed that the variables, including pathology, degree of differentiation, maximum short diameter of lymph node, tumor diameter, pulmonary membrane invasion, clustered lymph nodes, and T stage, were more significant for LNM prediction. Multifactorial logistic regression analysis for the GL model indicated that vascular invasion, tumor diameter, degree of differentiation, pulmonary membrane invasion, and maximum standard uptake value (SUVmax) were positively associated with LNM. The AUC for the RF model and GL model was 0.83 (95% CI: 0.75 to 0.90) and 0.64 (95% CI: 0.60 to 0.70), respectively.

Conclusion: We successfully established an accurate and optimized RF model that could be used to predict LNM in patients with NSCLC. This model can be used to evaluate the risk of an individual patient experiencing LNM and therefore facilitate the choice of treatment.
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http://dx.doi.org/10.2147/CMAR.S313941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217594PMC
June 2021

Characterization of underutilized root starches from eight varieties of ramie (Boehmeria nivea) grown in China.

Int J Biol Macromol 2021 Jul 21;183:1475-1485. Epub 2021 May 21.

Joint International Research Laboratory of Agriculture & Agri-Product Safety of the Ministry of Education, Yangzhou University, Yangzhou 225009, China. Electronic address:

Ramie root is an underutilized starch source. In this study, eight ramie varieties were investigated for starch properties. Starch content ranged from 18.6% to 50.1% in dry root. Starches from different varieties showed similar morphology including ellipsoidal, spherical and truncated granules with size D[4,3] from 10.1 to 14.1 μm. Starch had amylose content from 20.8% to 28.5%. All ramie varieties had B-type starches with relative crystallinity from 24.8% to 27.1%, ordered degree from 0.724 to 0.897 and lamellar thickness from 9.1 to 9.6 nm. Starches had gelatinization peak temperature from 70.5 to 73.8 °C and enthalpy from 14.9 to 15.8 J/g. Starches had swelling power and water solubility from 27.9 to 31.9 g/g and from 11.7% to 15.5%, respectively, at 95 °C, and exhibited different pasting properties with breakdown viscosity from 36 to 377 mPa s and setback viscosities from 1295 to 1863 mPa s. Starch pastes exhibited pseudoplastic behavior and different rheological properties. Native, gelatinized and retrograded starches had resistant starch from 81.7% to 83.9%, from 1.7% to 5.1% and from 5.6% to 13.3%, respectively. The eight varieties were divided into 3 groups according to starch properties. This study is helpful for selecting suitable ramie variety as starch source.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.126DOI Listing
July 2021

Astragalus polysaccharide protects formaldehyde-induced toxicity by promoting NER pathway in bone marrow mesenchymal stem cells.

Folia Histochem Cytobiol 2021 19;59(2):124-133. Epub 2021 May 19.

Department of Pathology, School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu, China.

Introduction: In our previous study, it has been confirmed that formaldehyde (FA) not only inhibits the proliferative activity, but also causes DNA-protein crosslinks (DPCs) formation in bone marrow mesenchymal stem cells (BMSCs). The purpose of this study was to detect the protective effect of astragalus polysaccharide (APS) against the cytotoxicity and genotoxicity of BMSCs exposed to FA, and to explore potential molecular mechanisms of APS activity.

Material And Methods: Human BMSCs were cultured in vitro and randomly divided into control cells (Ctrl group), FA-treated cells (FA group, 120 μmol/L), and cells incubated with FA and increasing concentrations (40, 100, or 400 μg/mL) of APS (FA + APS groups). Cytotoxicity was measured by MTT assay. DNA strand breakage, DNA-protein crosslinks (DPCs), and micronucleus formation were respectively detected by comet assay, KCl-SDS precipitation assay, and micronucleus assay. The mRNA and protein expression level of xeroderma pigmentosum group A (XPA), xeroderma pigmentosum group C (XPC), excision repair cross-complementation group 1 (ERCC1), replication protein A1 (RPA1), and replication protein A2 (RPA2) were all detected by qRT-PCR and Western Blot.

Results: Compared with the FA group, the cytotoxicity, DNA strand breakage, DPCs, and micronucleus levels were decreased significantly in FA + APS groups (P < 0.01). Meanwhile, the mRNA and protein expression of XPA, XPC, ERCC1, RPA1, and RPA2 were up regulated significantly in the FA + APS groups (P < 0.05) with the most prominent effect of the 100 μg/mL APS.

Conclusions: Our results suggest that APS can protect the cytotoxicity and genotoxicity of human BMSCs induced by FA. The mechanism may be associated with up-regulated expression of XPA, XPC, ERCC1, RPA1, and RPA2 in the nucleotide excision repair (NER) pathway which promotes DNA damage repair.
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http://dx.doi.org/10.5603/FHC.a2021.0013DOI Listing
September 2021

Clinical relevance of serum immunoglobulin G4 in glucocorticoid therapy of Graves' ophthalmopathy.

Clin Endocrinol (Oxf) 2021 10 16;95(4):657-667. Epub 2021 Jul 16.

Department of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Objective: Previous study suggested IgG4 levels were associated with the development of Graves' ophthalmopathy (GO). The aims of the present study were to investigate the role of IgG4 levels in glucocorticoid (GC) treatment in GO patients.

Design: 69 GO patients were enrolled. Serum thyroid hormones, thyroid antibodies, IgG, IgG4, ophthalmological examinations and orbital MRI were performed. Furthermore, the clinical outcomes (a composite response endpoint including the clinical activity score (CAS), proptosis, vision, intraocular pressure, diplopia and lid width) after high-dose intravenous GC treatment in 32 active moderate-to-severe GO patients were compared.

Patients: 69 consecutive patients with GO were asked to participate in the study. 32 of 69 GO patients were treated with high-dose intravenous GCs.

Measurements: Measurement of serum IgG and IgG4, serum thyroid hormones and thyroid autoantibodies. An overall ophthalmic assessment was performed pretherapy (week 0) and post-therapy (week 12).

Results: 33.3% of GO patients (23/69) had elevated IgG4 levels. IgG4 levels were positively correlated with the severity and activity of GO. After GC therapy, IgG4, IgG4/IgG, vision and CAS were significantly improved in GO patients. Patients with high IgG4 levels had a significantly reduced extraocular muscle area (EOMs) and better clinical outcomes than patients with normal IgG4 levels.

Conclusions: Our results suggest a possible subgroup of elevated IgG4 GO patients, with more severe ophthalmopathy and better response to GCs treatment compare with normal IgG4 GO patients.
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http://dx.doi.org/10.1111/cen.14493DOI Listing
October 2021

An Efficient Method for the Differentiation of Human iPSC-Derived Endoderm toward Enterocytes and Hepatocytes.

Cells 2021 04 6;10(4). Epub 2021 Apr 6.

Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

The endoderm, differentiated from human induced pluripotent stem cells (iPSCs), can differentiate into the small intestine and liver, which are vital for drug absorption and metabolism. The development of human iPSC-derived enterocytes (HiEnts) and hepatocytes (HiHeps) has been reported. However, pharmacokinetic function-deficiency of these cells remains to be elucidated. Here, we aimed to develop an efficient differentiation method to induce endoderm formation from human iPSCs. Cells treated with activin A for 168 h expressed higher levels of endodermal genes than those treated for 72 h. Using activin A (days 0-7), CHIR99021 and PI-103 (days 0-2), and FGF2 (days 3-7), the hiPSC-derived endoderm (HiEnd) showed 97.97% CD-117 and CD-184 double-positive cells. Moreover, HiEnts derived from the human iPSC line Windy had similar or higher expression of small intestine-specific genes than adult human small intestine. Activities of the drug transporter P-glycoprotein and drug-metabolizing enzyme cytochrome P450 (CYP) 3A4/5 were confirmed. Additionally, Windy-derived HiHeps expressed higher levels of hepatocyte- and pharmacokinetics-related genes and proteins and showed higher CYP3A4/5 activity than those derived through the conventional differentiation method. Thus, using this novel method, the differentiated HiEnts and HiHeps with pharmacokinetic functions could be used for drug development.
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http://dx.doi.org/10.3390/cells10040812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067398PMC
April 2021

The correlation between selenium levels and autoimmune thyroid disease: a systematic review and meta-analysis.

Ann Palliat Med 2021 Apr 16;10(4):4398-4408. Epub 2021 Apr 16.

Department of Internal Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Background: This investigation systematically evaluated the selenium levels and the effects of selenium supplementation in patients with autoimmune thyroid disease (AITD).

Methods: Randomized controlled trials (RCTs) related to selenium supplementation in patients with AITD were selected from the PubMed, Medline, Web of Sciences, Embase, Cochrane Library, and Spring databases. All related literature published between January 2000 and November 2020 were included. The RCT bias risk assessment was conducted according to the Cochrane Handbook 5.0.2. The Review Manager 5.3 software was applied for meta-analysis of the included literature.

Results: A total of 17 articles meeting the requirements were selected, including a total of 1,911 subjects. Meta-analysis results showed that the serum free triiodothyronine (FT3) levels in patients was greatly reduced after selenium supplementation compared to placebo treatment (MD =-0.40; 95% confidential interval (CI): -0.70--0.10; Z=2.61; P=0.009). Serum free thyroxine (FT4) levels and anti-thyroid peroxidase antibody (TPOAb) levels were also significantly reduced (MD = -0.76; 95% CI: -1.58--0.07; Z=1.79; P=0.07), and anti-thyroid peroxidase antibody (TPOAb) level was decreased observably (MD =-150.25; 95% CI: -04.06--96.43; Z=5.47; P<0.00001). The thyroid stimulating hormone (TSH) levels (MD =0.06; 95% CI: -0.53-0.66; Z=0.21; P=0.83) and anti-thyroglobulin antibody (TGAb) levels (MD =17.19; 95% CI: -254.86-289.25; Z=0.12; P=0.90) were not significantly different between the experimental group and the control group.

Conclusions: Selenium-containing drugs were effective in treating AITD patients, and greatly reduced the levels of FT3, FT4, and TPOAb in AITD patients. These results suggested that selenium level had a great effect on AITD and selenium supplementation showed a very important effect on AITD.
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http://dx.doi.org/10.21037/apm-21-449DOI Listing
April 2021

First isolation of vancomycin-resistant Enterococcus faecalis from cattle and swine in Xinjiang, China.

J Infect 2021 07 16;83(1):119-145. Epub 2021 Apr 16.

College of Animal Science and Technology, Shihezi University, Shihezi, Xinjian 832000, People's Republic of China; Key Laboratory of Control and Prevention of Animal Disease, Xinjiang Production and Construction Corps, Shihezi 832000, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.04.006DOI Listing
July 2021

Tentacle-type poly(hydroxamic acid)-modified macroporous cellulose beads: Synthesis, characterization, and application for heavy metal ions adsorption.

J Chromatogr A 2021 May 26;1645:462098. Epub 2021 Mar 26.

Department of Pharmaceutical & Biological Engineering, School of Chemical Engineering, Sichuan University, Chengdu 610065, PR China. Electronic address:

Herein, a facile yet efficient template method to fabricate macroporous cellulose beads (MCBs) is reported. In this method, micro-size CaCO is utilized to create macroporous structure for fast mass transfer, and tentacle-type poly(hydroxamic acid) as adsorption ligand is immobilized on the MCBs to improve adsorption capacity. The obtained tentacle-type poly(hydroxamic acid)-modified MCMs (TP-CMCBs) show uniform spherical shape (about 80 μm), bimodal pore system (macropores≈3.0 μm; diffusional pores≈14.5 nm), and high specific surface area (52.7 m/g). The adsorption performance of TP-CMCBs is evaluated by heavy metal ions adsorption. TP-CMCBs exhibit not only high adsorption capacities (342.5, 261.5 and 243.2 mg/g for Cu, Mn and Ni, respectively.), but also fast adsorption rate (>70% of its equilibrium uptake within 30 min). Additionally, TP-CMCBs have excellent reusability, as evidenced by that the adsorption capacities have no obvious change even after five-time consecutive adsorption-desorption cycles. All results demonstrate that the proposed TP-CMCBs have great potential in removal of heavy metal ions.
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http://dx.doi.org/10.1016/j.chroma.2021.462098DOI Listing
May 2021

Comparative efficacy of various preventive methods for exposure keratopathy among critically ill patients: A network meta-analysis of randomized controlled trials.

Int J Nurs Stud 2021 Jun 10;118:103926. Epub 2021 Mar 10.

Department of Nursing, The Affiliated Hospital of Guizhou Medical University, No. 28 GuiyiRoad, Yunyan District, Guiyang 550000, China. Electronic address:

Background: There is a wide variety of preventive methods currently available for the treatment of exposure keratopathy. Because of a lack of evidence from head-to-head randomized controlled trials (RCTs), the relative effects of these preventive methods in exposure keratopathy patients remain unclear. The purpose of our study is to carry out a network meta-analysis comparing the efficacy of different methods for the prevention of exposure keratopathy and rank these nursing methods for practical consideration.

Methods: A literature search was performed of the MEDLINE (PubMed), EMBASE, Web of Science, China National Knowledge Infrastructure Library (CNKI), China Science and Technology Journal Database (Weipu), WanFang Database and China Biology Medicine disc. Two authors independently extracted data from each included RCTs according to a predesigned Excel spreadsheet and assessed the methodological quality of included RCTs using the Cochrane risk of bias tool. Data was analyzed using the R (V.3.6.2) and the Stata (V.15.0).

Results: 21 RCTs involving 2022 patients and evaluating 11 preventive methods were included. Rankings based on posterior probabilities revealed that artificial tear ointment might be the best way to prevent exposure keratopathy (35%), polyethylene covers might be the second-best (31%), swimming goggles might be the third-best (21%), foam dressing might be the fourth-best (18%).

Conclusions: This network meta-analysis indicated that artificial tear ointment, polyethylene covers, swimming goggles and foam dressing might be selected for the prevention of exposure keratopathy in intensive care unit patients, which is important in future research. Although evidence is scant, more attention should be paid to head-to-head comparisons of the most commonly used prevention methods in this field.
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http://dx.doi.org/10.1016/j.ijnurstu.2021.103926DOI Listing
June 2021

Clinical outcomes and influencing factors of PD-1/PD-L1 in hepatocellular carcinoma.

Oncol Lett 2021 Apr 10;21(4):279. Epub 2021 Feb 10.

Department of Pharmacy, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China.

Hepatocellular carcinoma (HCC) has an increasing incidence worldwide, and the global 5-year survival rate ranges from 5-30%. In China, HCC seriously threatens the nation's health; the incidence of HCC ranks fourth among all theriomas, and the mortality rate is the third highest worldwide. The main therapies for HCC are surgical treatment or liver transplantation; however, most patients with HCC will experience postoperative recurrence or metastasis, eventually resulting in mortality. As for advanced or unresectable HCC, the current appropriate treatment strategy is transarterial chemoembolization; however, limited therapeutic effect and natural or acquired drug resistance affect the efficacy of this approach. Previous studies have demonstrated that PD-L1 expression on host cells and myeloid cells plays an important role in PD-L1 blocked-mediated tumor regression. Thus, further research on programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) is required. Countries including the United States, France, Britain and China have developed PD-1/PD-L1 blockers, including nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, toripalimab, sintilimab and camrelizumab. Notably, all of these blockers have therapeutic effect and influencing factors in HCC. Factors that influence the clinical outcome of PD-1 have also been discovered, such as inflammatory genes, specific receptors and signaling pathways. The discovery of these factors will help to identify novel methods, such as combination treatment, to decrease the influence of other factors on the efficacy of PD-1/PD-L1. Sorafenib and lenvatinib have been approved for first-line treatment for patients with advanced HCC. When first-line treatment frequently fails, pembrolizumab and ipilimumab plus nivolumab are used following sorafenib (but not lenvatinib) treatment in advanced HCC. Thus, tumor immunotherapy using PD-1/PD-L1 blockers exhibits promising outcomes for the treatment of HCC, and more novel PD-1/PD-L1 inhibitors are being developed to fight against this disease. The present review discusses the clinical results and influencing factors of PD-1/PD-L1 inhibitors in HCC to provide insight into the development and optimization of PD-1/PD-L1 inhibitors in the treatment of HCC.
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http://dx.doi.org/10.3892/ol.2021.12540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905537PMC
April 2021

H2S improves doxorubicin-induced myocardial fibrosis by inhibiting oxidative stress and apoptosis via Keap1-Nrf2.

Technol Health Care 2021 ;29(S1):195-209

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.

Objective: We waimed to investigate whether H2S can relieve the myocardial fibrosis caused by doxorubicin through Keap1-Nrf2.

Methods: Sprague-Dawley (SD) rats were randomly divided into four groups: normal control group (Control); DOX model group (DOX); H2S intervention model group (DOX+H2S); H2S control group (H2S). DOX and DOX+H2S group were injected with doxorubicin (3.0 mg/kg/time) intraperitoneally. Both of the Control group and H2S groups were given normal saline in equal volume, 2 weeks later, DOX+H2S and H2S group were controlled with NaHS (56 μmol/kg/d) through the abdominal cavity, while the Control and DOX group were injected with normal saline of the same dosage intraperitoneally.

Results: Myocardial injury and myocardial cell apoptosis were significantly increased, the H2S content in myocardial tissue was remarkably down-regulated, the expression levels of MDA, Keap1, caspase-3, caspase-9, TNF-α, IL1β, MMPs and TIMP-1 in rat myocardial tissue was significantly up-regulated (P< 0.05), and the expression levels of GSH, NQO1, Bcl-2 were down-regulated compared with those of control group. The above results can be reversed by the DOX+H2S group. There is no statistically significant difference between the Control group and the H2S control group.

Conclusions: These results suggest that H2S can improve DOX-induced myocardial fibrosis in rats, and the keap1/Nrf2 signaling pathway, oxidative stress, inflammation, and apoptosis may be involved in the mechanism.
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http://dx.doi.org/10.3233/THC-218020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150551PMC
August 2021

Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway.

Mol Med Rep 2021 04 2;23(4). Epub 2021 Mar 2.

Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.

The present study aimed to determine the role and regulatory mechanism of hydrogen sulfide (HS) in the amelioration of doxorubicin‑induced myocardial fibrosis in rats. It is hypothesized that the PI3K/AKT/mTOR signaling pathway is regulated to inhibit endoplasmic reticulum stress (ERS) and autophagy to reduce myocardial fibrosis. A total of 40 adult male Sprague Dawley rats were randomly divided into 4 groups (n=10/group). The 4 groups included the normal control group (control group), model group [doxorubicin (Dox) group], HS intervention model group (HS+Dox group) and HS control group (HS group). The model used in the present study was constructed by administering intraperitoneal injections of doxorubicin (3.0 mg/kg every other day; total of 6 injections). In addition, the intervention factor, NaHS and the donor of HS, was also administered by intraperitoneal injection (56 µmol/kg/day), which lasted a month. Pathological changes in the rats were observed using Masson staining and transmission electron microscopy, while the protein expression levels of MMPs/TIMPs, transforming growth factor‑β1, cystathionine lyase and PI3K/AKT/mTOR, which are autophagy‑related and ERS‑related proteins were detected in myocardial tissues using western blot analysis. The gene expression levels of collagen type I α‑2 chain and collagen type III α‑1 chain were detected using reverse transcription‑quantitative PCR and the quantification of myocardial HS content was performed using ELISA. In the Dox group compared with that in the control group, myocardial fibers were significantly disordered, while the protein expression levels of ERS‑related and autophagy‑related proteins were increased markedly, and the expression levels of PI3K/AKT/mTOR proteins were reduced markedly. The aforementioned changes were markedly reversed following HS intervention, which indicated that HS exerts a positive protective effect on doxorubicin‑induced myocardial fibrosis. The protective mechanism of HS intervention in myocardial fibrosis is hypothesized to be associated with the inhibition of overactivation of the ER and that of autophagy via upregulation of the PI3K/AKT/mTOR pathway.
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http://dx.doi.org/10.3892/mmr.2021.11938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930940PMC
April 2021
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