Publications by authors named "Zhe Chen"

1,069 Publications

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DG-8d, a novel diosgenin derivative, decreases the proliferation and induces the apoptosis of A549 cells by inhibiting the PI3k/Akt signaling pathway.

Steroids 2021 Jul 30:108898. Epub 2021 Jul 30.

Qiqihaer Medical University, Heilongjiang Qiqihaer 161006, China. Electronic address:

Lung neoplasm has a relatively poor prognosis, and the clinical efficacy of targeted medicine remains unsatisfactory. Therefore, the development of novel efficient anti-lung cancer drugs is urgently needed. In our previous study, we showed that a novel diosgenin derivative 8d (DG-8d), which contained 5-(3-pyridyl)-1,3,4-thiadiazole moiety, had significant cytotoxic activity on human tumor cells, especially the A549 cells. However, the underlying mechanism of DG-8d was unknown. In this study, the pharmacological effect of DG-8d on the A549 cells was inspected.

Method: Cell viability and apoptosis were detected by CCK-8 assays, morphological changes and quantitative analysis of flow cytometry. Levels of gene and protein expression of apoptosis-related and PI3k/Akt pathway were evaluated by qRT-PCR, immunostaining and Western blot analysis.

Result: The findings proved that DG-8d could inhibit cell growth and induce apoptosis. The effect of DG-8d on the proliferation and apoptosis in the A549 cells were improved with LY294002 (PI3K inhibitor). Moreover, the effect of DG-8d on apoptosis was further confirmed by AO-EB dye, mitochondrial depolarization and accrued intracellular ROS. Gene and protein detection showed that DG-8d or DG-8d combined with LY294002 could down-regulate signaling molecules of Bcl-2, PI3k, p-Akt, p-FoxO3a and up-regulate signaling molecules of Bax snd Bim. In addition, nuclear translocation of FoxO3a was observed significantly in the cells.

Conclusion: DG-8d could inhibit the proliferation and induce the apoptosis of the A549 cells, which maybe mainly because of the suppression of the PI3k/Akt pathways. Finally, we believe that DG-8d can be developed as a possible agent for carcinoma therapy.
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http://dx.doi.org/10.1016/j.steroids.2021.108898DOI Listing
July 2021

Exploring the Clinical Characteristics of COVID-19 Clusters Identified Using Factor Analysis of Mixed Data-Based Cluster Analysis.

Front Med (Lausanne) 2021 16;8:644724. Epub 2021 Jul 16.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

The COVID-19 outbreak has brought great challenges to healthcare resources around the world. Patients with COVID-19 exhibit a broad spectrum of clinical characteristics. In this study, the Factor Analysis of Mixed Data (FAMD)-based cluster analysis was applied to demographic information, laboratory indicators at the time of admission, and symptoms presented before admission. Three COVID-19 clusters with distinct clinical features were identified by FAMD-based cluster analysis. The FAMD-based cluster analysis results indicated that the symptoms of COVID-19 were roughly consistent with the laboratory findings of COVID-19 patients. Furthermore, symptoms for mild patients were atypical. Different hospital stay durations and survival differences among the three clusters were also found, and the more severe the clinical characteristics were, the worse the prognosis. Our aims were to describe COVID-19 clusters with different clinical characteristics, and a classifier model according to the results of FAMD-based cluster analysis was constructed to help provide better individualized treatments for numerous COVID-19 patients in the future.
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http://dx.doi.org/10.3389/fmed.2021.644724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323882PMC
July 2021

Assessment of carbon emissions of building interior decoration and renovation waste disposal in the fast-growing Greater Bay Area, China.

Sci Total Environ 2021 Jul 23;798:149158. Epub 2021 Jul 23.

College of Civil & Transportation Engineering, Underground Polis Academy, Shenzhen University, Shenzhen 518060, China. Electronic address:

Continuing urbanization and significant improvement of lifestyle have ushered in high demand for building floor area, inevitably leading to a rapid increase of interior decoration and renovation activities, which in turn produce a massive quantity of decoration and renovation waste (DRW). However, like many other countries with unremitting demand for building space and infrastructure, China has failed to attach adequate attention to DRW management. Using the yield-per-area method and life cycle assessment approach, this study aims to characterize the generation, flows, management and environmental impacts of DRW from commercial housing in nine cities in the Greater Bay Area (GBA), a highly developed economic zone in China. The results show that the production of DRW in the GBA increased from 0.16 million metric tons (Mt) in 1999 to 2.6 (±10%) Mt in 2018, with an annual growth rate of 16%. Ninety-five percent of the DRW is directly disposed of via simple landfilling. Although the recycling rate is relatively low, it still generated a benefit of 119,000 tons COeq mitigation in 2018. According to scenario-based analysis, improving the recycling rate and encouraging the use of prefabricated decoration could go a long way toward tackling the DRW problem. These findings can help reveal the full impacts of DRW in the GBA, and also provide a reference for other cities to take action.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149158DOI Listing
July 2021

Genome-wide characterization and expression profiling of B3 superfamily during ethylene-induced flowering in pineapple (Ananas comosus L.).

BMC Genomics 2021 Jul 21;22(1):561. Epub 2021 Jul 21.

Key Laboratory of Tropical Fruit Tree Biology of Hainan Province, Institute of Tropical Fruit Trees, Hainan Academy of Agricultural Sciences, Haikou, 571100, China.

Background: The B3 superfamily (B3s) represents a class of large plant-specific transcription factors, which play diverse roles in plant growth and development process including flowering induction. However, identification and functional surveys of B3 superfamily have not been reported in ethylene-induced pineapple flowering (Ananas comosus).

Results: 57 B3 genes containing B3 domain were identified and phylogenetically classified into five subfamilies. Chromosomal localization analysis revealed that 54 of 57 AcB3s were located on 21 Linkage Groups (LG). Collinearity analysis demonstrated that the segmental duplication was the main event in the evolution of B3 gene superfamily, and most of them were under purifying selection. The analysis of cis-element composition suggested that most of these genes may have function in response to abscisic acid, ethylene, MeJA, light, and abiotic stress. qRT-PCR analysis of 40 AcB3s containing ethylene responsive elements exhibited that the expression levels of 35 genes were up-regulated within 1 d after ethephon treatment and some were highly expressed in flower bud differentiation period in stem apex, such as Aco012003, Aco019552 and Aco014401.

Conclusion: This study provides a basic information of AcB3s and clues for involvement of some AcB3s in ethylene-induced flowering in pineapple.
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http://dx.doi.org/10.1186/s12864-021-07854-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296579PMC
July 2021

Voice Emotion Recognition by Mandarin-Speaking Children with Cochlear Implants.

Ear Hear 2021 Jul 7. Epub 2021 Jul 7.

Department of Otolaryngology, Head and Neck Surgery, Peking University First Hospital, Beijing, China.

Objectives: Emotional expressions are very important in social interactions. Children with cochlear implants can have voice emotion recognition deficits due to device limitations. Mandarin-speaking children with cochlear implants may face greater challenges than those speaking nontonal languages; the pitch information is not well preserved in cochlear implants, and such children could benefit from child-directed speech, which carries more exaggerated distinctive acoustic cues for different emotions. This study investigated voice emotion recognition, using both adult-directed and child-directed materials, in Mandarin-speaking children with cochlear implants compared with normal hearing peers. The authors hypothesized that both the children with cochlear implants and those with normal hearing would perform better with child-directed materials than with adult-directed materials.

Design: Thirty children (7.17-17 years of age) with cochlear implants and 27 children with normal hearing (6.92-17.08 years of age) were recruited in this study. Participants completed a nonverbal reasoning test, speech recognition tests, and a voice emotion recognition task. Children with cochlear implants over the age of 10 years also completed the Chinese version of the Nijmegen Cochlear Implant Questionnaire to evaluate the health-related quality of life. The voice emotion recognition task was a five-alternative, forced-choice paradigm, which contains sentences spoken with five emotions (happy, angry, sad, scared, and neutral) in a child-directed or adult-directed manner.

Results: Acoustic analyses showed substantial variations across emotions in all materials, mainly on measures of mean fundamental frequency and fundamental frequency range. Mandarin-speaking children with cochlear implants displayed a significantly poorer performance than normal hearing peers in voice emotion perception tasks, regardless of whether the performance is measured in accuracy scores, Hu value, or reaction time. Children with cochlear implants and children with normal hearing were mainly affected by the mean fundamental frequency in speech emotion recognition tasks. Chronological age had a significant effect on speech emotion recognition in children with normal hearing; however, there was no significant correlation between chronological age and accuracy scores in speech emotion recognition in children with implants. Significant effects of specific emotion and test materials (better performance with child-directed materials) in both groups of children were observed. Among the children with cochlear implants, age at implantation, percentage scores of nonverbal intelligence quotient test, and sentence recognition threshold in quiet could predict recognition performance in both accuracy scores and Hu values. Time wearing cochlear implant could predict reaction time in emotion perception tasks among children with cochlear implants. No correlation was observed between the accuracy score in voice emotion perception and the self-reported scores of health-related quality of life; however, the latter were significantly correlated with speech recognition skills among Mandarin-speaking children with cochlear implants.

Conclusions: Mandarin-speaking children with cochlear implants could have significant deficits in voice emotion recognition tasks compared with their normally hearing peers and can benefit from the exaggerated prosody of child-directed speech. The effects of age at cochlear implantation, speech and language development, and cognition could play an important role in voice emotion perception by Mandarin-speaking children with cochlear implants.
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http://dx.doi.org/10.1097/AUD.0000000000001085DOI Listing
July 2021

A risk factor-based predictive model for linezolid-induced anaemia: A 7-year retrospective study.

J Clin Pharm Ther 2021 Jul 20. Epub 2021 Jul 20.

Department of Pharmacy, Zhongshan Hospital, FuDan University, Shanghai, China.

What Is Known And Objective: The primary adverse reaction of linezolid is haematological toxicity, leading to thrombocytopenia and anaemia. This study aimed to investigate the risk factors of linezolid-induced anaemia (LI-AN) and establish a predictive model by multivariate logistic regression model analysis to predict LI-AN risks in Chinese adult patients.

Methods: Demographic and clinical data of patients who underwent linezolid therapy for more than three days between January 2014 and December 2020 in Zhongshan Hospital, Fudan University, were retrieved from the hospital's electronic medical record for analysis. Multivariate logistic regression analysis was employed to establish a predictive model, whose predictability was further evaluated by the area under the receiver operating characteristic (ROC) curve.

Results And Discussion: The study comprised 298 patients among the 2322 patients who underwent linezolid treatment between 2014 and 2020. Among the 298 patients, 32 (10.7%) developed anaemia with an average of 11.4 (SD 6.2) days after the initiation of linezolid therapy. Multivariate logistic analysis revealed that age ≥60 years (odds ratio [OR] 2.815, 95% confidence interval [CI] 1.242-6.379), higher total bilirubin (TBi) (OR 1.031, 95% CI 1.011-1.051), eGFR < 60 ml/(min·1.73 m ) (OR 2.537, 95% CI 1.054-6.106), duration of linezolid therapy (DLT) (OR 1.091, 95% CI 1.023-1.163) and intensive care unit (ICU) admittance (OR 2.664, 95% CI 1.150-6.174) were the independent risk factors for anaemia occurrence among patients receiving linezolid therapy. A logistic regression equation based on the five risk factors was subsequently established and transformed to obtain the calculation formula of the combined predictor: Y  = X  + 34.5 × X  + 31.1 × X  + 32.7 × X  + 2.9 × X , (where Age ≥60 years, yes = 1, no = 0; eGFR < 60 ml/(min·1.73 m ), yes = 1, no = 0; ICU admittance, yes = 1, no = 0). The area under the ROC curve of the combined predictors equation was 0.773 with an optimal cut-off point value of 92.4, corresponding to a 75.0% sensitivity and 76.7% specificity.

What Is New And Conclusion: LI-AN is associated with age (≥60 years), higher TBi, eGFR < 60 ml/(min·1.73 m ), DLT and ICU admittance. Physicians should thus calculate the combined predictor value at the beginning of linezolid treatment to predict and evaluate the risk of LI-AN. An optimal cut-off value larger than 92.4 indicates that the patient has a higher LI-AN risk. As such, Hb levels should be monitored regularly, and dosage regimens adjusted accordingly to prevent anaemia occurrence. This study provides an evidence-based logistic model that reduces LI-AN incidences and promotes the safe clinical use of linezolid.
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http://dx.doi.org/10.1111/jcpt.13495DOI Listing
July 2021

Evaluation of the reporting quality of clinical practice guidelines on gliomas using the RIGHT checklist.

Ann Transl Med 2021 Jun;9(12):1002

Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The reporting quality of clinical practice guidelines (CPGs) for gliomas has not yet been thoroughly assessed. The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) statement developed in 2016 provides a reporting framework to improve the quality of CPGs. We aimed to estimate the reporting quality of glioma guidelines using the RIGHT checklist and investigate how the reporting quality differs by selected characteristics.

Methods: We systematically searched electronic databases, guideline databases, and medical society websites to retrieve CPGs on glioma published between 2018 and 2020. We calculated the compliance of the CPGs to individual items, domains and the RIGHT checklist overall. We performed stratified analyses by publication year, country of development, reporting of funding, and impact factor (IF) of the journal.

Results: Our search revealed 20 eligible guidelines. Mean overall adherence to the RIGHT statement was 54.6%. Eight CPGs reported more than 60% of the items, and five reported less than 50%. All guidelines adhered to the items 1a, 3, 7a, 13a, while no guidelines reported the items 17 or 18b (see http://www.right-statement.org/right-statement/checklist for a description of the items). Two of the seven domains, "Basic information" and "Background", had mean reporting rates above 60%. The "Review and quality assurance" domain had the lowest mean reporting rate, 12.5%. The reporting quality of guidelines published in 2020, guidelines developed in the United States, and guidelines that reported funding tended to be above average.

Conclusions: The reporting quality of CPGs on gliomas is low and needs improvement. Particular attention should be paid on reporting the external review and quality assurance process. The use of the RIGHT criteria should be encouraged to guide the development, reporting and evaluation of CPGs.
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http://dx.doi.org/10.21037/atm-21-2604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267264PMC
June 2021

Broadband mode-selective couplers based on tapered side-polished fibers.

Opt Express 2021 Jun;29(13):19690-19702

We propose the broadband mode-selective coupler (MSC) formed with a side-polished six mode fiber (6MF) and a tapered side-polished small core single-mode fiber (SC-SMF) or an SMF. The MSCs are designed to allow the LP mode in the SC-SMF and SMF to completely couple to the LP, LP, LP, LP, LP, LP modes in the 6MF over a broadband wavelength range. The phase-matching conditions of the MSCs are satisfied by tapering the SC-SMF and SMF to specific diameters. The tapered fibers are side-polished to designed residual fiber thickness using the wheel polishing technique. The effective indices of the side-polished fibers are measured with the prism coupling method. The MSCs provide high coupling ratio and high mode purity. High coupling efficiencies in excess of 81% for all the higher-order modes are obtained in the wavelength range 1530-1600 nm. For the LP, LP, LP, LP, LP, LP MSCs at 1550 nm, the coupling ratios are 96.2%, 99.8%, 89.5%, 85.0%, 90.9%, 96.1%, respectively, and the mode purity of the MSCs is higher than 88.0%. The loss of the MSCs is lower than 1.8 dB in the wavelength range 1530-1600 nm. This device can be applied in broadband mode-division multiplexing transmission systems.
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http://dx.doi.org/10.1364/OE.426698DOI Listing
June 2021

The impact of a closed-loop thalamocortical model on the spatiotemporal dynamics of cortical and thalamic traveling waves.

Sci Rep 2021 Jul 13;11(1):14359. Epub 2021 Jul 13.

Department of Psychiatry, Department of Neuroscience and Physiology, Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, 10016, USA.

Propagation of activity in spatially structured neuronal networks has been observed in awake, anesthetized, and sleeping brains. How these wave patterns emerge and organize across brain structures, and how network connectivity affects spatiotemporal neural activity remains unclear. Here, we develop a computational model of a two-dimensional thalamocortical network, which gives rise to emergent traveling waves similar to those observed experimentally. We illustrate how spontaneous and evoked oscillatory activity in space and time emerge using a closed-loop thalamocortical architecture, sustaining smooth waves in the cortex and staggered waves in the thalamus. We further show that intracortical and thalamocortical network connectivity, cortical excitation/inhibition balance, and thalamocortical or corticothalamic delay can independently or jointly change the spatiotemporal patterns (radial, planar and rotating waves) and characteristics (speed, direction, and frequency) of cortical and thalamic traveling waves. Computer simulations predict that increased thalamic inhibition induces slower cortical frequencies and that enhanced cortical excitation increases traveling wave speed and frequency. Overall, our results provide insight into the genesis and sustainability of thalamocortical spatiotemporal patterns, showing how simple synaptic alterations cause varied spontaneous and evoked wave patterns. Our model and simulations highlight the need for spatially spread neural recordings to uncover critical circuit mechanisms for brain functions.
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http://dx.doi.org/10.1038/s41598-021-93618-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277909PMC
July 2021

Shuanghuanglian oral preparations combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: A systematic review and meta-analysis of randomized controlled trials.

PLoS One 2021 13;16(7):e0254405. Epub 2021 Jul 13.

Department of Pediatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Background: Mycoplasma pneumoniae is one of the main causes of community-acquired pneumonia. Due to the imperfect immune system of children, this also causes Mycoplasma pneumoniae pneumonia (MPP) to be more common in children. Globally, the incidence of MPP in children is gradually increasing. This study was the first to systematically review the clinical efficacy and safety of Shuanghuanglian (SHL) oral preparations combined with azithromycin in the treatment of MPP in children.

Methods: This study fully retrieved 3 Chinese databases and 5 English databases to search the randomized controlled trials (RCTs) of SHL oral preparations combined with azithromycin in the treatment of children with MPP. The search time is from the inception to September 2020. Data extraction and risk bias evaluation were performed independently by two researchers. We conducted a Meta-analysis of all the outcome indicators. Besides, Meta-regression, subgroup analysis, and heterogeneity analysis were used for the primary outcomes to find the possible potential confounding factors.

Results: Finally, we included 27 RCTs involving 2884 patients. SHL oral preparations combined with azithromycin were better than azithromycin alone in response rate (RR = 1.14, 95% CI[1.11, 1.18]; low certainty evidence), disappearance time of fever(MD = -1.72, 95% CI[-2.47, -0.97]; low certainty evidence), disappearance time of cough (MD = -2.95, 95% CI[-3.55, -2.34]; low certainty evidence), and disappearance time of pulmonary rales (MD = -2.13, 95% CI[-2.88, -1.38]; low certainty evidence). The Meta-regression results showed that the course of disease, age, and method of administration may be the source of heterogeneity. Subgroup analysis and sensitivity analysis have found that the results were stable. For other related clinical symptoms, T lymphocytes, and Serum inflammatory factors, SHL oral preparations combined with azithromycin was better than azithromycin alone, and the difference was statistically significant. For adverse events with low certainty evidence, safety needs further verification.

Conclusion: Based on the results of meta-analysis with low certainty evidence, we believed that SHL oral preparations combined with azithromycin likely be effectively improved clinical symptoms compared with azithromycin alone. Low certainty evidence showed that SHL may safety with no serious adverse events. Due to these limitations, the safety needs further verification. More high-quality, multicenter, and large-sample RCTs should be tested and verified in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254405PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277054PMC
July 2021

Potential Implications of Quercetin in Autoimmune Diseases.

Front Immunol 2021 23;12:689044. Epub 2021 Jun 23.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.
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http://dx.doi.org/10.3389/fimmu.2021.689044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260830PMC
June 2021

How personal characteristics impact phishing susceptibility: The mediating role of mail processing.

Appl Ergon 2021 Jul 8;97:103526. Epub 2021 Jul 8.

CAS Key Laboratory of Behavioral Science, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China. Electronic address:

In the phishing email literature, recent researchers have given much attention to individual differences in phishing susceptibility from the perspective of the Big Five personality traits. Although the effectiveness and advantages of the phishing susceptibility measures in the signal detection theory (SDT) framework have been verified, the cognitive mechanisms that lead to individual differences in these measures remain unknown. The current study proposed and examined a theoretical path model to explore how the Big Five personality traits, related knowledge and experience and the cognitive processing of emails (i.e., mail elaboration) influence users' susceptibility to phishing emails. A sample of 414 Chinese participants completed the 44-item Big Five Personality Inventory (BFI-44), Mail Elaboration Scale (MES), Web Experience Questionnaire, Experience with Electronic Mail Scale, Knowledge and Technical Background Test and a demographic questionnaire. The phishing susceptibility measures were calculated after the participants finished an email legitimacy task in a role-playing scenario. The results showed that the general profile of the "victim personality" included low conscientiousness, low openness and high neuroticism, and Internet experience and computer and web knowledge played an important role. All of these factors have significant indirect effects on phishing susceptibility by influencing mail elaboration. Moreover, the probabilities of checking for further information or deleting the email reflect the sensitivity of email judgment. These findings reveal the mediating role of cognitive processing between individual factors and phishing susceptibility. The theoretical implications of this study for the phishing susceptibility literature and its applications to phishing risk interventions or training programs are discussed.
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http://dx.doi.org/10.1016/j.apergo.2021.103526DOI Listing
July 2021

Application of bedside ultrasound in predicting the outcome of weaning from mechanical ventilation in elderly patients.

BMC Pulm Med 2021 Jul 9;21(1):217. Epub 2021 Jul 9.

Department of Respiratory and Critical Care Medicine, Beijing Haidian Hospital, No. 29, Zhongguancun St, Haidian District, Beijing, 100080, China.

Background: With the increased ageing of society, more and more elderly people are admitted to the intensive care unit, How to accurately predict whether elderly patients can successfully wean from the ventilator is more complicated. Diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were measured by bedside ultrasound to assess diaphragm function. The lung ultrasound score (LUS) and the rapid shallow breathing index (RBSI) were used as indices of diaphragm function to predict the outcome of weaning from mechanical ventilation. The aim of this study was to examine the clinical utility of these parameters in predicting extubation success.

Methods: This prospective study included 101 consecutive elderly patients undergoing a trial of extubation in the ICU of Haidian Hospital between June 2017 and July 2020. Patients were divided into the successful weaning group (n = 69) and the failed weaning group (n = 32). Baseline characteristics, including RSBI, were recorded. Measurements of DE, DTF and LUS were made using ultrasound within 24 h before extubation.

Results: Median DE was greater in patients with extubation success than in those with extubation failure (1.64 cm vs. 0.78 cm, p = 0.001). Patients with extubation success had a greater DTF than those with extubation failure (49.48% vs. 27.85%, p = 0.001). The areas under the receiver operating curves for the RSBI, LUS, DE and DFT were 0.680, 0.764, 0.831 and 0.881, respectively. The best cut-off values for predicting successful weaning were DTF ≥ 30%, DE ≥ 1.3 cm, LUS ≤ 11, and RSBI ≤ 102. The specificity of DTF (84%) in predicting weaning outcome was higher than that of RBSI (53%), that of LUS (55%), and that of DE (62%). The sensitivity of DTF (94%) was greater than that of RBSI (85%), that of LUS (71%), and that of DE (65%). The combination of RSBI, LUS, DE, and DTF showed the highest AUC (AUC = 0.919), with a sensitivity of 96% and a specificity of 89%.

Conclusions: DTF has higher sensitivity and specificity for the prediction of successful weaning in elderly patients than the other parameters examined. The combination of RSBI, LUS, DE and DFT performed well in predicting weaning outcome. This has potentially important clinical application and merits further evaluation.
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http://dx.doi.org/10.1186/s12890-021-01605-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267769PMC
July 2021

A novel Keap1 inhibitor iKeap1 activates Nrf2 signaling and ameliorates hydrogen peroxide-induced oxidative injury and apoptosis in osteoblasts.

Cell Death Dis 2021 Jul 5;12(7):679. Epub 2021 Jul 5.

Department of Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

An ultra-large structure-based virtual screening has discovered iKeap1 as a direct Keap1 inhibitor that can efficiently activate Nrf2 signaling. We here tested its potential effect against hydrogen peroxide (HO)-induced oxidative injury in osteoblasts. In primary murine and human osteoblasts, iKeap1 robustly activated Nrf2 signaling at micromole concentrations. iKeap1 disrupted Keap1-Nrf2 association, causing Nrf2 protein stabilization, cytosol accumulation and nuclear translocation in murine and human osteoblasts. The anti-oxidant response elements (ARE) activity and transcription of Nrf2-ARE-dependent genes (including HO1, NQO1 and GCLC) were increased as well. Significantly, iKeap1 pretreatment largely ameliorated HO-induced reactive oxygen species production, lipid peroxidation and DNA damage as well as cell apoptosis and programmed necrosis in osteoblasts. Moreover, dexamethasone- and nicotine-induced oxidative injury and apoptosis were alleviated by iKeap1. Importantly, Nrf2 shRNA or CRISPR/Cas9-induced Nrf2 knockout completely abolished iKeap1-induced osteoblast cytoprotection against HO. Conversely, CRISPR/Cas9-induced Keap1 knockout induced Nrf2 cascade activation and mimicked iKeap1-induced cytoprotective actions in murine osteoblasts. iKeap1 was ineffective against HO in the Keap1-knockout murine osteoblasts. Collectively, iKeap1 activated Nrf2 signaling cascade to inhibit HO-induced oxidative injury and death of osteoblasts.
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http://dx.doi.org/10.1038/s41419-021-03962-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257690PMC
July 2021

Apelin/APJ signaling activates autophagy to promote human lung adenocarcinoma cell migration.

Life Sci 2021 Sep 26;281:119763. Epub 2021 Jun 26.

Institute of Pharmacy and Pharmacology, College of Basic Medical Science, Hengyang Medical College, University of South China, Hengyang, China. Electronic address:

Aims: Beclin1(BECN1) is known as an autophagy-related protein and the expression is promoted by apelin in lung adenocarcinoma cells, suggesting that apelin activates autophagy in lung adenocarcinoma. However, the functions of apelin-induced autophagy in lung adenocarcinoma tumorigenesis and deterioration are still unknown. Thus, this study aims to investigate the effects of apelin-induced autophagy on lung adenocarcinoma tumorigenesis and deterioration.

Main Methods: Protein expression of exogenous genes were detected by Western blotting analysis. Lung adenocarcinoma cell migration was assessed with cell migration assays. Autophagy was measured with quantification of GFP-LC3 or RFP-GFP-LC3 puncta using fluorescence microscopy in cells by an observed blinded to experimental condition and by western blot analysis of LC3 and p62 in cell lysates as well as autophagy flux. Immunofluorescence staining was performed in human lung adenocarcinoma A549 cells with p-cofilin antibody. The proteins expression in cancer specimens were examined with immunohistochemistry.

Key Findings: Here, we reveal that apelin induces autophagy activation in lung adenocarcinoma. Apelin/APJ regulates BECN1 transcription via HIF1A. Apelin/APJ-activated autophagy promotes lung adenocarcinoma cell migration. Moreover, treatment with autophagy inhibitors significantly decreases apelin/APJ-induced lung adenocarcinoma cell migration. Evaluation of patient samples of lung adenocarcinoma reveals an association between APJ with BECN1 expression and a poor prognosis.

Significance: Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.
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http://dx.doi.org/10.1016/j.lfs.2021.119763DOI Listing
September 2021

A prototype closed-loop brain-machine interface for the study and treatment of pain.

Nat Biomed Eng 2021 Jun 21. Epub 2021 Jun 21.

Department of Anesthesiology, Perioperative Care and Pain, New York University School of Medicine, New York, NY, USA.

Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.
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http://dx.doi.org/10.1038/s41551-021-00736-7DOI Listing
June 2021

[Comparison of the effectiveness of the posterior malleolus fixed or not on treatment of different Haraguchi's classification of posterior malleolus fractures].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jun;35(6):722-728

Department of Spinal Surgery, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou Zhejiang, 310000, P.R.China.

Objective: To investigate the effectiveness of fixation the posterior malleolus or not to treat different Haraguchi's classification of posterior malleolus fractures.

Methods: The clinical data of 86 trimalleolar fracture patients who were admitted between January 2015 and September 2019 and met the selection criteria were retrospectively reviewed. There were 29 males and 57 females; the age ranged from 26 to 82 years with a mean age of 55.2 years. According to Haraguchi's classification, 38 patients were in type Ⅰ group, 30 patients in type Ⅱ group, and 18 patients in type Ⅲ group. There was no significant difference in the general data such as gender, age, and fracture location among the 3 groups ( >0.05). The fixation of the posterior malleolus was performed in 23, 21, and 5 patients in type Ⅰ, Ⅱ, and Ⅲ groups, respectively. The operation time, fracture healing time, full weight-bearing time, postoperative joint flatness, and joint degeneration degree of the patients in each group were recorded and compared. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to evaluate ankle function, including pain, quality of daily life, joint range of motion, and joint stability. The AOFAS scores were compared between fixation and non-fixation groups in each group.

Results: The procedure was successfully completed by all patients in each group, and there was no significant difference in operation time ( =3.677, =0.159). All patients were followed up 12-36 months with a mean time of 16.8 months. At last follow-up, 6 patients were found to have suboptimal ankle planarity, including 2 patients (5.3%) in the type Ⅰ group and 4 patients (13.3%) in the type Ⅱ group, with no significant difference between groups ( =6.566, =0.161). The ankle joints of all the patients in each group showed mild degeneration; the fractures all healed well and no delayed union or nonunion occurred. There was no significant difference in the fracture healing time and full weight-bearing time between groups ( >0.05). No complications such as incision infection, fracture displacement, or plate screw loosening and fracture occurred during follow-up. At last follow-up, the total scores and pain scores of the AOFAS scores in the type Ⅱ group were significantly lower than those in the type Ⅰand Ⅲ groups ( <0.05), there was no significant difference between groups in the scores for the quality of daily life, joint range of motion, and joint stability between groups ( >0.05). There was no significant difference in any of the scores between the unfixed and fixed groups, except for the pain and quality of daily life scores, which were significantly lower ( <0.05) in the unfixed group of type Ⅱ group than the fixed group.

Conclusion: Haraguchi type Ⅱ posterior malleolus fractures have a worse prognosis than types Ⅰ and Ⅲ fractures, especially in terms of postoperative pain, which can be significantly improved by fixing the posterior malleolus; the presence or absence of posterior malleolus fixation in types Ⅰ and Ⅲ has less influence on prognosis.
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http://dx.doi.org/10.7507/1002-1892.202012114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218178PMC
June 2021

Adaptive compounding speckle-noise-reduction filter for optical coherence tomography images.

J Biomed Opt 2021 Jun;26(6)

Universidad Politécnica de Madrid, ETSI Telecomunicación, Biomedical Image Technologies Laboratory,, Spain.

Significance: Speckle noise limits the diagnostic capabilities of optical coherence tomography (OCT) images, causing both a reduction in contrast and a less accurate assessment of the microstructural morphology of the tissue.

Aim: We present a speckle-noise reduction method for OCT volumes that exploits the advantages of adaptive-noise wavelet thresholding with a wavelet compounding method applied to several frames acquired from consecutive positions. The method takes advantage of the wavelet representation of the speckle statistics, calculated properly from a homogeneous sample or a region of the noisy volume.

Approach: The proposed method was first compared quantitatively with different state-of-the-art approaches by being applied to three different clinical dermatological OCT volumes with three different OCT settings. The method was also applied to a public retinal spectral-domain OCT dataset to demonstrate its applicability to different imaging modalities.

Results: The results based on four different metrics demonstrate that the proposed method achieved the best performance among the tested techniques in suppressing noise and preserving structural information.

Conclusions: The proposed OCT denoising technique has the potential to adapt to different image OCT settings and noise environments and to improve image quality prior to clinical diagnosis based on visual assessment.
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http://dx.doi.org/10.1117/1.JBO.26.6.065001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211087PMC
June 2021

Blocking the JAK2/STAT3 and ERK pathways suppresses the proliferation of gastrointestinal cancers by inducing apoptosis.

J Zhejiang Univ Sci B 2021 Jun;22(6):492-503

Key Laboratory of Digestive Pathophysiology of Zhejiang Province, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310006, China.

Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.
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http://dx.doi.org/10.1631/jzus.B2000842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214945PMC
June 2021

Fear extinction learning modulates large-scale brain connectivity.

Neuroimage 2021 Sep 11;238:118261. Epub 2021 Jun 11.

Department of Psychiatry, New York University School of Medicine, New York, NY, United States; The Neuroscience Institute, New York University School of Medicine, New York, NY, United States; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States. Electronic address:

Exploring the neural circuits of the extinction of conditioned fear is critical to advance our understanding of fear- and anxiety-related disorders. The field has focused on examining the role of various regions of the medial prefrontal cortex, insular cortex, hippocampus, and amygdala in conditioned fear and its extinction. The contribution of this 'fear network' to the conscious awareness of fear has recently been questioned. And as such, there is a need to examine higher/multiple cortical systems that might contribute to the conscious feeling of fear and anxiety. Herein, we studied functional connectivity patterns across the entire brain to examine the contribution of multiple networks to the acquisition of fear extinction learning and its retrieval. We conducted trial-by-trial analyses on data from 137 healthy participants who underwent a two-day fear conditioning and extinction paradigm in a functional magnetic resonance imaging (fMRI) scanner. We found that functional connectivity across a broad range of brain regions, many of which are part of the default mode, frontoparietal, and ventral attention networks, increased from early to late extinction learning only to a conditioned cue. The increased connectivity during extinction learning predicted the magnitude of extinction memory tested 24 h later. Together, these findings provide evidence supporting recent studies implicating distributed brain regions in learning, consolidation and expression of fear extinction memory in the human brain.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118261DOI Listing
September 2021

Running Promotes Transformation of Brain Astrocytes Into Neuroprotective Reactive Astrocytes and Synaptic Formation by Targeting Gpc6 Through the STAT3 Pathway.

Front Physiol 2021 21;12:633618. Epub 2021 May 21.

Department of Cardiothoracic Surgery, Xiangya Changde Hospital, Changde, China.

Ischemic stroke is caused by cerebral ischemia upon the blockage of an artery, which results in a high disability rate. Little is known regarding the mechanism of astrocyte function in cerebral ischemia. We aimed to determine the effects of running on the transformation of astrocytes, and subsequent synapse formation. A study of middle cerebral artery occlusion (MCAO) after running showed that running can promote the transformation of astrocytes toward the neuroprotective phenotype. Our findings of oxygen-glucose deprived astrocytes after running revealed that these astrocytes transformed into the neuroprotective phenotype, and that the expression of STAT3 and Gpc6 was increased. We confirmed that mechanistically, running can target Gpc6 through the STAT3 pathway and then regulate the number of synapses. We concluded that running promotes synapse proliferation by polarizing astrocytes toward the neuroprotective phenotype and ultimately leads to nerve regeneration.
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http://dx.doi.org/10.3389/fphys.2021.633618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189178PMC
May 2021

Traditional Chinese Medicine Oral Liquids Combined With Azithromycin for Pneumonia in Children: A Bayesian Network Meta-Analysis.

Front Pharmacol 2021 28;12:652412. Epub 2021 May 28.

Evidence-Based Medicine Center, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

pneumonia (MPP) causes flu-like symptoms in children, increasing the burden on the health and education systems. In China, traditional Chinese medicine oral liquids (TCMOLs) combined with azithromycin (TCMOLs + Azithromycin) is commonly used to treat MPP in children. However, TCMOLs with the optimal clinical applicability remain unknown. Here, we evaluated the clinical effectiveness and safety of TCMOLs + Azithromycin in children with MPP. We searched PubMed, Embase, Cochrane Library, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for eligible randomized controlled trials (RCTs) published from database inception to October 2020. Two reviewers independently performed data extraction and risk of bias assessment. After Bayesian random effect modeling and surface under the cumulative ranking curve (SUCRA) scoring, we ranked each intervention. We assessed heterogeneity using multivariate meta-regression for potential modifiers and used the Grading of Recommendations, Assessment, Development, and Evaluation to rate pooled evidence's certainty. In the 63 included RCTs with 6,410 children, five different TCMOLs were combined with azithromycin. TCMOLs + Azithromycin had significantly better primary outcomes than did azithromycin alone. Of all TCMOLs, Xiaoer Xiaoji Zhike (XEXJZK)+Azithromycin showed the best effectiveness with respect to the response rate (odds ratio [OR] = 6.5, 95% credible interval [CrI] = 4.3-10; low certainty) and pulmonary rales disappearance time (mean difference [MD] = -2.1, 95% CrI: -2.9 to -1.2; low certainty) with SUCRA 85 and 80%, respectively. Pudilan Xiaoyan + Azithromycin showed the highest effectiveness with respect to cough disappearance time (MD = -2.6, 95% CrI: -3.4 to -1.7; very low certainty) and fever disappearance time (MD = -1.8, 95% CrI: -2.3 to -1.3; very low certainty) with SUCRA 87 and 87%, respectively. The difference in the adverse effects between TCMOLs + Azithromycin and azithromycin alone was nonsignificant. Of the different TCMOLs, XEXJZK may be the best option to combine with azithromycin to treat children with MPP. However, our results should be interpreted with caution due to the low certainty of evidence. In general, TCMOLs' safety remains unclear because of a lack of evidence. More high-quality RCTs are needed to further evaluate efficacy and safety of these TCMOLs.
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http://dx.doi.org/10.3389/fphar.2021.652412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194818PMC
May 2021

Sec62 promotes pro-angiogenesis of hepatocellular carcinoma cells under hypoxia.

Cell Biochem Biophys 2021 Jun 12. Epub 2021 Jun 12.

Department of Traditional Chinese Medicine, Changhai Hospital, Naval Medical University, Shanghai, China.

This study aimed to investigate the underlying molecular pathogenic mechanism of Sec62 in hepatocellular carcinoma (HCC). Microarray analysis was conducted to profile the global gene expression in the HCC cell line Huh7 cells transfected with Sec62 vs. NC and Sec62 vs. NC. Ingenuity pathway analysis and gene set enrichment analysis were used to perform Sec62-related signaling pathway analysis from screened differentially expressed genes (DEGs). A protein-protein interaction network was constructed. Experimental validation of the expression of key DEGs was conducted. Hypoxia-induced tube formation was undertaken to investigate the role of Sec62 in angiogenesis. A total of 74 intersected DEGs were identified from Huh7 cells with Sec62 vs. NC and Sec62 vs. NC. Among them, 65 DEGs were correlated with the expression of Sec62. The P53 signaling pathway was found to be enriched in Huh7 cells with Sec62 vs. NC, while the acute phase response signaling pathway was enriched in Huh7 cells with Sec62 vs. NC. DEGs, such as serine protease inhibitor E (SERPINE) and tumor necrosis factor receptor superfamily, member 11B (TNFRSF11B), were not only identified as the lead genes of these enriched pathways, but were also found to be closely related to Sec62. Moreover, knockdown of Sec62 decreased the expression of SERPINE1 (plasminogen activator inhibitor type 1 (PAI-1)) and TNFRSF11B, whereas overexpression of Sec62 had the opposite effects. In addition, knockdown of Sec62 inhibited hypoxia-induced tube formation via PAI-1. Sec62 promoted pro-angiogenesis of HCC under hypoxia by regulating PAI-1, and it may be a crucial angiogenic switch in HCC.
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http://dx.doi.org/10.1007/s12013-021-01008-6DOI Listing
June 2021

Cross-Modality Imaging of Murine Tumor Vasculature-a Feasibility Study.

Mol Imaging Biol 2021 Jun 8. Epub 2021 Jun 8.

Austrian BioImaging/CMI, Vienna BioCenter Core Facilities GmbH (VBCF), Vienna, Austria.

Tumor vasculature and angiogenesis play a crucial role in tumor progression. Their visualization is therefore of utmost importance to the community. In this proof-of-principle study, we have established a novel cross-modality imaging (CMI) pipeline to characterize exactly the same murine tumors across scales and penetration depths, using orthotopic models of melanoma cancer. This allowed the acquisition of a comprehensive set of vascular parameters for a single tumor. The workflow visualizes capillaries at different length scales, puts them into the context of the overall tumor vessel network and allows quantification and comparison of vessel densities and morphologies by different modalities. The workflow adds information about hypoxia and blood flow rates. The CMI approach includes well-established technologies such as magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and ultrasound (US), and modalities that are recent entrants into preclinical discovery such as optical coherence tomography (OCT) and high-resolution episcopic microscopy (HREM). This novel CMI platform establishes the feasibility of combining these technologies using an extensive image processing pipeline. Despite the challenges pertaining to the integration of microscopic and macroscopic data across spatial resolutions, we also established an open-source pipeline for the semi-automated co-registration of the diverse multiscale datasets, which enables truly correlative vascular imaging. Although focused on tumor vasculature, our CMI platform can be used to tackle a multitude of research questions in cancer biology.
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http://dx.doi.org/10.1007/s11307-021-01615-yDOI Listing
June 2021

Reactive Oxygen Species Mediate Low Back Pain by Upregulating Substance P in Intervertebral Disc Degeneration.

Oxid Med Cell Longev 2021 14;2021:6681815. Epub 2021 May 14.

Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), Henan Provincial Orthopedic Institute, Zhengzhou 450000, China.

Reactive oxygen species (ROS) are thought to have a strong correlation with a number of intervertebral disc (IVD) diseases. Here, we aimed to determine whether ROS represent an etiology of low back pain (LBP) during IVD degeneration. Thirty degenerated intervertebral disc samples were obtained from patients, and ROS levels were quantified using dihydroethidium (DHE) staining. The results suggested a significant correlation between the ROS level and the severity of LBP. Subsequently, a puncture-induced LBP model was established in rats, and ROS levels significantly increased compared with those in the sham surgery group, accompanied with severe puncture-induced IVD degeneration. In addition, when ROS levels were increased by HO administration or decreased by NAC treatment, the rats showed increased or decreased LBP, respectively. Based on this evidence, we further determined that stimulation with HO in nucleus pulposus cells (NPCs) or resulted in upregulation of substance P (SP), a peptide thought to be involved in the synaptic transmission of pain, and that the severity of LBP decreased when SP levels were increased by exogenous SP administration or neutralized via aprepitant treatment in the IVDs of rats. In conclusion, ROS are primary inducers of LBP based on clinical and animal data, and the mechanism involves ROS stimulation of NPCs to secrete SP, which is a critical neurotransmitter peptide, to promote LBP in IVDs. Therefore, reducing the level of ROS with specific drugs and inhibiting SP may be alternative methods to treat LBP in the clinic.
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http://dx.doi.org/10.1155/2021/6681815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140854PMC
May 2021

Formosanin C promotes the curative efficacy of ultrasound-guided radiofrequency ablation in a mouse model of breast cancer.

Oncol Lett 2021 Jul 24;22(1):550. Epub 2021 May 24.

Department of Ultrasound, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China.

Breast cancer is the leading cause of tumor-associated death among women worldwide, and new therapeutic strategies are required to improve the post-surgery prognosis and quality of life of patients. Radiofrequency ablation (RFA) is a less invasive approach compared with traditional surgical resection to treat malignancies, and the combination of RFA and chemotherapeutic agents, including formosanin C (FC), can synergistically improve the curative effects against breast carcinoma. However, the detailed mechanisms remain unclear. In the present study, nude mice were used to identify the influence of FC on the therapeutic efficacy of RFA for breast cancer. Flow cytometry was performed to demonstrate the proportional alteration of CD8 and CD45 T cells with different biomarkers, including CD107a, IFNγ and TNFα. It was demonstrated that FC enhanced the therapeutic efficacy of RFA in breast cancer, while RFA combined with FC improved the proportion of IFNγ and TNFα CD8 T cells and CD107a CD8 T cells in tumor-infiltrating lymphocytes, thus increasing the immune responses caused by surgery and chemotherapy. The present study indicated that FC may promote the curative efficacy of ultrasound-guided RFA against breast tumor by regulating adaptive immune responses.
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http://dx.doi.org/10.3892/ol.2021.12811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170285PMC
July 2021

[Meta-analysis of clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in treatment of hypertensive left ventricular hypertrophy].

Zhongguo Zhong Yao Za Zhi 2021 May;46(10):2578-2587

Tianjin University of Traditional Chinese Medicine Tianjin 301617, China Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.

To systematically evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy. China National Knowledge Infrastructure(CNKI), Wanfang, VIP, PubMed, EMbase, Cochrane Library, Ovid and Web of Science databases were searched by computer to retrieve the randomized controlled trials(RCTs) of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy from the establishment of databases to July 2020. After two researchers performed data retrieval, data extraction, and risk assessment of bias, they used RevMan 5.3 software for Meta-analysis. A total of 10 RCTs were included, with a total of 979 patients. Meta-analysis results showed that in terms of interventricular septal thickness(MD=-0.70, 95%CI[-1.15,-0.24], P=0.003), left ventricular posterior wall thickness(MD=-0.81, 95%CI[-1.41,-0.21], P=0.008), left ventricular mass index(MD=-8.75, 95%CI[-17.40,-0.10], P=0.05), systolic blood pressure(MD=-8.97, 95%CI[-13.46,-4.48], P<0.000 1), diastolic blood pressure(MD=-5.87, 95%CI[-8.39,-3.34], P<0.000 01) and left ventricular end-diastolic diameter(MD=-1.73, 95%CI[-2.38,-1.08], P<0.000 01), Compound Danshen Dripping Pills combined with conventional antihypertensive drugs was superior to conventional antihypertensive drugs. In terms of left ventricular ejection fraction(MD=0.41, 95%CI[-0.74, 1.55], P=0.49), there was no statistical difference in treatment between the two groups. Because of the small amount of literatures included in the safety aspect, it is impossible to give an accurate conclusion. The GRADE score showed that the level of evidence was low and extremely low. The results show that the Compound Danshen Dripping Pills combined with conventional antihypertensive drugs may effectively improve the clinical efficacy for hypertensive ventricular hypertrophy, and the safety needs to be further explored. Due to the low quality of the included literatures, more high-quality RCTs are needed for verification.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210222.502DOI Listing
May 2021

Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis.

J Ethnopharmacol 2021 May 20;279:114213. Epub 2021 May 20.

Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, China. Electronic address:

Ethnopharmacological Relevance: Herba taxilli (HT, Sangjisheng in Chinese), which is composed of the dried stems and leaves of Taxillus chinensis (DC.) Danser, has been commonly used to treat inflammation and arthritis in traditional Chinese medicine (TCM). Quercetin (Que) is a major active flavonoid component isolated from HT and is one of the quality control indexes of HT. In the clinical practice of TCM, formulas containing HT are commonly used to treat rheumatoid arthritis (RA). Recent studies have shown that Que exerts antiarthritic effects. However, the mechanism by which Que treatment affects RA is not fully understood.

Aim Of The Study: This study aimed to explore the antiarthritic activity of Que in a collagen-induced arthritis (CIA) mouse model and investigate the underlying mechanisms.

Materials And Methods: The antiarthritic activity of Que was evaluated in a CIA mouse model by determining the paw clinical arthritis scores and left ankle thicknesses and by conducting micro-PET imaging and histopathological analysis of ankle joint tissues. The proinflammatory cytokine (IL-6, TNF-α, IL-1β, IL-8, IL-13, IL-17) levels in the serum and ankle joint tissues were measured by ELISA. Mitochondrial oxidative stress was assessed by biochemical methods. Mitochondrial biogenesis was analysed by RT-qPCR. The protein levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), p38, phospho-p38, extracellular signal-regulated kinases (ERK)-1/2, phospho-ERK1/2, p65, and phospho-p65 in ankle joint tissues were detected by Western blot analysis. A total of 30 RA patients were recruited to investigate the relationship between the disease activity score (DAS28) and the SIRT1, PGC-1α, NRF1, and HMGB1 plasma levels.

Results: Que treatment decreased the clinical score and left ankle thickness of CIA mice, attenuated the synovial inflammation and hyperplasia and bone/cartilage destruction in ankle joints, and decreased the secretion of IL-6, TNF-α, IL-1β, IL-8, IL-13, and IL-17. Mechanistically, Que treatment improved impaired mitochondrial biogenesis and mitochondrial function by regulating the SIRT1/PGC-1α/NRF1/TFAM pathway and inhibited inflammation via the HMGB1/TLR4/p38/ERK1/2/NF-κB p65 pathway. Notably, epidemiological data revealed correlations between abnormal circulating levels of SIRT1, PGC-1α, NRF1, HMGB1 and RA disease activity in patients.

Conclusions: Our data suggested a potential role of Que as a dietary therapeutic drug for RA treatment that may act through SIRT1 to target mitochondrial biogenesis. Additionally, the role of impaired mitochondrial biogenesis in RA was evaluated.
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http://dx.doi.org/10.1016/j.jep.2021.114213DOI Listing
May 2021

Mechanically Robust and UV-Curable Shape-Memory Polymers for Digital Light Processing Based 4D Printing.

Adv Mater 2021 Jul 17;33(27):e2101298. Epub 2021 May 17.

Shenzhen Key Laboratory of Biomimetic Robotics and Intelligent Systems, Department of Mechanical and Energy Engineering, Southern University of Science and Technology, Shenzhen, 518055, China.

4D printing is an emerging fabrication technology that enables 3D printed structures to change configuration over "time" in response to an environmental stimulus. Compared with other soft active materials used for 4D printing, shape-memory polymers (SMPs) have higher stiffness, and are compatible with various 3D printing technologies. Among them, ultraviolet (UV)-curable SMPs are compatible with Digital Light Processing (DLP)-based 3D printing to fabricate SMP-based structures with complex geometry and high-resolution. However, UV-curable SMPs have limitations in terms of mechanical performance, which significantly constrains their application ranges. Here, a mechanically robust and UV-curable SMP system is reported, which is highly deformable, fatigue resistant, and compatible with DLP-based 3D printing, to fabricate high-resolution (up to 2 µm), highly complex 3D structures that exhibit large shape change (up to 1240%) upon heating. More importantly, the developed SMP system exhibits excellent fatigue resistance and can be repeatedly loaded more than 10 000 times. The development of the mechanically robust and UV-curable SMPs significantly improves the mechanical performance of the SMP-based 4D printing structures, which allows them to be applied to engineering applications such as aerospace, smart furniture, and soft robots.
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http://dx.doi.org/10.1002/adma.202101298DOI Listing
July 2021
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