Publications by authors named "Yan Li"

12,544 Publications

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Clinical study on swallowing function of brainstem stroke by tDCS.

Neurol Sci 2021 May 11. Epub 2021 May 11.

Department of Medical Imaging, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 Xianxia Road, Shanghai, 200336, China.

Objective: To investigate the effect of transcranial direct current stimulation (tDCS) combined with conventional comprehensive rehabilitation on dysphagia after brainstem stroke.

Materials And Methods: Forty brainstem stroke patients were randomly divided into tDCS group and conventional comprehensive treatment group, including 20 patients in each group. Both groups were given routine swallowing function training, and tDCS group added transcranial direct current stimulation (tDCS). The Dysphagia Outcome and Severity Scale (DOSS) and Functional Dysphagia Scale (FDS) were evaluated respectively before and after 8 weeks of continuous treatment with VFSS. The white blood cell (WBC), c-reactive protein, prealbumin (PAB), albumin (Alb), and hemoglobin (Hb) were also compared between the two groups before and after 8 weeks of continuous treatment.

Results: After 8 consecutive weeks of treatment, the score of DOSS scale and FDS scale in both groups was improved (P < 0.05), WBC and CRP were decreased (P < 0.05), and Alb and Hb were improved (P < 0.05), and PAB had no differences (P=0.474). The tDCS group was superior to conventional comprehensive group in improving the swallowing function and nutritional indexes (P < 0.05).

Conclusions: tDCS therapy combined with routine training can improve the swallowing function and nutritional status of patients, and reduce infection.
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http://dx.doi.org/10.1007/s10072-021-05247-6DOI Listing
May 2021

Spin-polarized oxygen evolution reaction under magnetic field.

Nat Commun 2021 May 10;12(1):2608. Epub 2021 May 10.

School of Material Science and Engineering, Nanyang Technological University, Singapore, Singapore.

The oxygen evolution reaction (OER) is the bottleneck that limits the energy efficiency of water-splitting. The process involves four electrons' transfer and the generation of triplet state O from singlet state species (OH or HO). Recently, explicit spin selection was described as a possible way to promote OER in alkaline conditions, but the specific spin-polarized kinetics remains unclear. Here, we report that by using ferromagnetic ordered catalysts as the spin polarizer for spin selection under a constant magnetic field, the OER can be enhanced. However, it does not applicable to non-ferromagnetic catalysts. We found that the spin polarization occurs at the first electron transfer step in OER, where coherent spin exchange happens between the ferromagnetic catalyst and the adsorbed oxygen species with fast kinetics, under the principle of spin angular momentum conservation. In the next three electron transfer steps, as the adsorbed O species adopt fixed spin direction, the OER electrons need to follow the Hund rule and Pauling exclusion principle, thus to carry out spin polarization spontaneously and finally lead to the generation of triplet state O. Here, we showcase spin-polarized kinetics of oxygen evolution reaction, which gives references in the understanding and design of spin-dependent catalysts.
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http://dx.doi.org/10.1038/s41467-021-22865-yDOI Listing
May 2021

Correction to: Dexmedetomidine attenuates myocardial ischemia-reperfusion injury in vitro by inhibiting NLRP3 Inflammasome activation.

BMC Anesthesiol 2021 May 10;21(1):141. Epub 2021 May 10.

Shandong Provincial Medicine and Health Key Laboratory of Clinical Anesthesia, School of Anesthesiology, Weifang Medical University, No. 7166, Baotong West Street, Weicheng District, Weifang, 261021, China.

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http://dx.doi.org/10.1186/s12871-021-01356-zDOI Listing
May 2021

Psychometric Properties of the Exercise Orientation Questionnaire: A Confirmatory Study on Chinese University Students.

Front Public Health 2021 22;9:574335. Epub 2021 Apr 22.

The Branch of the Collaborative Innovation Center of Assessment Toward Basic Education Quality, Southwest University, Chongqing, China.

The Exercise Orientation Questionnaire (EOQ) is a method for evaluating individuals' exercise attitudes and behaviors associated with exercise motivation. A lack of exercise motivation can affect physical activity attitudes, behavior, and action among university students. Physical inactivity may lead to health risks. The purpose of this study was to assess the measurement of psychological properties in the EOQ and to determine the reliability and validity of the EOQ when applied to Chinese university students. A total of 368 university students (male 48.8%) aged between 17 and 23 years ( = 19.60, = 1.18) participated in the current study. Confirmatory factor analysis (CFA) and exploratory structural equation modeling (ESEM) were used to verify the factorial validity of the EOQ. The internal consistency coefficient (Cronbach's alpha and McDonald's omega) was used to determine reliability. Multiple regression analysis was used to test concurrent validity. The International Physical Activity Questionnaire (IPAQ) was used to determine the participants' level of physical activity. The range of the subscale coefficient was 0.80-0.89, and the total scale was 0.95, which indicated that the reliability of the EOQ was excellent. The research showed that the initial CFA model of the EOQ had poorly fitting indices. The corrected model after seven residual correlations achieved the setting standard, but the correlation coefficient between some factors exceeded the standard threshold, which indicated that the CFA fitting model was not ideal. ESEM is a combination of exploratory and verifiable analytical techniques. Using ESEM and abbreviated version CFA to analyze the data indicated that the model fitted well [ESEM: TLI = 0.97 > 0.90, CFI = 0.96 > 0.90, SRMR = 0.02 < 0.08, and RMSEA = 0.045 < 0.08 (90% CI 0.033-0.055); CFA: TLI = 0.92 > 0.90, CFI = 0.91 > 0.90, SRMR = 0.08, and RMSEA = 0.06 < 0.08 (90% CI 0.055-0.067)]. The results of multiple regression analysis suggested that the ESEM model was effective in distinguishing the differences between individuals with different levels of physical activity (PAL) and body mass index (BMI). Overall, the Chinese abbreviated version of the EOQ (EOQ-CA) was fond to be a reliable tool for monitoring the exercise attitudes and behaviors of Chinese University students.
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http://dx.doi.org/10.3389/fpubh.2021.574335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101286PMC
April 2021

The Immune-Related Gene HCST as a Novel Biomarker for the Diagnosis and Prognosis of Clear Cell Renal Cell Carcinoma.

Front Oncol 2021 23;11:630706. Epub 2021 Apr 23.

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga) and GEO (https://www.ncbi.nlm.nih.gov/geo/). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (https://www.immport.org/). Differential analysis with R software (https://www.r-project.org/) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (https://www.oncomine.org/), Human Protein Atlas (https://www.proteinatlas.org/), and PubMed (https://pubmed.ncbi.nlm.nih.gov/) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis ( < 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression ( < 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042-2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115-3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562-4.442) were independent risk factors affecting the OS of ccRCC patients (all, < 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.
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http://dx.doi.org/10.3389/fonc.2021.630706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103545PMC
April 2021

Contralateral axillary lymph node metastasis and molecular changes in second primary breast cancer: a case report.

Gland Surg 2021 Apr;10(4):1547-1552

Breast Disease Department, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Contralateral axillary metastasis (CAM) is rather rare in primary breast cancer. In this case, we present a 46-year-old female patient who underwent left breast-conserving surgery (BCS) and left axillary lymph node dissection (ALND). Two years later, an enlarged lymph node was found in her right axilla. Magnetic resonance imaging (MRI) of the breast displayed a left breast mass with multiple internal mammary lymph nodes and abnormal lymph nodes in the right axillary region. However, no abnormalities were found in the right breast. The left breast mass was diagnosed as invasive carcinoma by core needle biopsy. During the operation, we suggested that the contralateral lymph nodes were metastatic from the second primary breast cancer by preoperative 99mTc injection around the left breast. The patient underwent left mastectomy and right axillary lymph node dissection. The postoperative pathology was diagnosed as metachronous secondary primary left breast cancer, in which the initial presentation was lymph node metastasis to the contralateral axilla of the left breast. Therefore, we propose that CAM may be more common in second primary or recurrent breast cancer. It should be treated as locoregional extension. Preoperative lymph node markers are important to identify whether contralateral axillary lymph node metastasis occurs from a second primary breast cancer.
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http://dx.doi.org/10.21037/gs-20-708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102228PMC
April 2021

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal metastasis from breast cancer: a preliminary report of 4 cases.

Gland Surg 2021 Apr;10(4):1315-1324

Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Background: Breast cancer (BC) has the highest morbidity and the fifth-highest mortality rate among women in China. Peritoneal metastases from BC are rare, and presently, there are no guidelines or international consensus on its treatment. Patients with a prognosis of peritoneal carcinomatosis (PC) have poorer survival rates than patients with other regional metastases from BC.

Methods: Four BC PC patients, who had undergone cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), participated in this study. Clinicopathologic characteristics and overall survival (OS) data were collected and analyzed.

Results: Patients' average age when they underwent CRS + HIPEC was 59.8 years. The average time of CRS + HIPEC was 8.8 h. The median number of resected organ areas was 7. Following CRS + HIPEC, each of the 4 patients survived for 31, 28, 16 and 52 months, respectively. There were no serious adverse events during the perioperative period.

Conclusions: The study examined the detailed process of CRS + HIPEC and found that patients with BC PC may benefit from this treatment. The 4 cases provided evidence that the integrated therapy of CRS + HIPEC is a promising strategy that could improve outcomes for BC PC patients. Further, no serious adverse events (SAEs) occurred during the CRS + HIPEC perioperative period.
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http://dx.doi.org/10.21037/gs-20-893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102231PMC
April 2021

Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review.

J Gastrointest Oncol 2021 Apr;12(Suppl 1):S70-S78

Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China.

Peritoneal metastasis (PM) from gastric cancer (GC) has long been regarded as the terminal disease, lacking of effective treatments. In recent 40 years, cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and early post-operative intraperitoneal chemotherapy (EPIC), has been recommended as a preferred treatment option for some selected patients with GCPM. Intraperitoneal free cancer cells were recognized as the pathological cause of PM and the primary target for intraperitoneal chemotherapy. There were a lot of evidence demonstrating that HIPEC could effectively eradiate intraperitoneal free cancer cells and prolong overall survival in GCPM. However, there are still no standard HIPEC protocols. This review summarized the current HIPEC regimens used in GCPM from a literature search, trying to conclude the optimal HIPEC in GCPM, and indicate the future direction of HIPEC study. Moreover, the new data on the exploration of HIPEC in GCPM at Shijitan Hospital, Capital Medical University was shared. In conclusion, there was not enough evidence from publications and our own experience to conclude a recommended HIPEC regimen for GCPM. There is urgent need for standardizing HIPEC protocols worldwide. Accordingly, more international collaborations focusing on pharmacology and HIPEC-related parameters to generate high level evidence are essential.
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http://dx.doi.org/10.21037/jgo-20-262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100728PMC
April 2021

Agitation in a Microcarrier-based Spinner Flask Bioreactor Modulates Homeostasis of Human Mesenchymal Stem Cells.

Biochem Eng J 2021 Apr 27;168. Epub 2021 Jan 27.

Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida, United States.

Human mesenchymal stem cells (hMSCs) are well known in cell therapy due to their secretion of trophic factors, multipotent differentiation potential, and ability for self-renewal. As a result, the number of clinical trials has been steadily increasing over the last decade highlighting the need for in vitro systems capable of producing large quantities of cells to meet growing demands. However, hMSCs are highly sensitive to microenvironment conditions, including shear stress caused by dynamic bioreactor systems, and can lead to alteration of cellular homeostasis. In this study, hMSCs were expanded on microcarriers within a 125 mL spinner flask bioreactor system. Our results demonstrate a three-fold expansion over seven days. Furthermore, our results show that culturing hMSCs in the microcarrier-based suspension bioreactor (compared to static planar culture) results in smaller cell size and higher levels of reactive oxidative species (ROS) and ROS regulator Sirtuin-3, which have implications on the nicotinamide adenine dinucleotide metabolic pathway and metabolic homeostasis. In addition, hMSCs in the bioreactor showed the increased Prostaglandin E secretion as well as reduced the Indoleamine-pyrrole 2,3-dioxygenase secretion upon stimulus with interferon gamma. The results of this study provide understanding of potential hMSC physiology alterations impacted by bioreactor microenvironment during scalable production of hMSCs for biomanufacturing and clinical trials.
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http://dx.doi.org/10.1016/j.bej.2021.107947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104359PMC
April 2021

Overexpression of Toll-like receptor 4 contributes to the internalization and elimination of Escherichia coli in sheep by enhancing caveolae-dependent endocytosis.

J Anim Sci Biotechnol 2021 May 10;12(1):63. Epub 2021 May 10.

Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.

Background: Gram-negative bacterial infections have a major economic impact on both the livestock industry and public health. Toll-like receptor 4 (TLR4) plays a crucial role in host defence against Gram-negative bacteria. Exploring the defence mechanism regulated by TLR4 may provide new targets for treatment of inflammation and control of bacterial infections. In a previous study, we generated transgenic sheep overexpressing TLR4 by microinjection to improve disease resistance. The defence mechanism through which TLR4 overexpression protected these sheep against pathogens is still not fully understood.

Results: In the present study, we used Escherichia coli to infect monocytes isolated from peripheral blood of the animal model. The overexpression of TLR4 strongly enhanced the percentage of endocytosis and capacity of elimination in monocytes during the early stages of infection. This phenomenon was mainly due to overexpression of TLR4 promoting caveolae-mediated endocytosis. Pretreatment of the transgenic sheep monocytes with inhibitors of TLR4, Src signalling, or the caveolae-mediated endocytosis pathway reduced the internalization of bacteria, weakened the ability of the monocytes to eliminate the bacteria, and increased the pH of the endosomes.

Conclusion: Together, our results reveal the effects of TLR4 on the control of E. coli infection in the innate immunity of sheep and provide crucial evidence of the caveolae-mediated endocytosis pathway required for host resistance to invading bacteria in a large animal model, providing theoretical support for breeding disease resistance in the future. Furthermore, Src and caveolin 1 (CAV1) could be potentially valuable targets for the control of infectious diseases.
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http://dx.doi.org/10.1186/s40104-021-00585-zDOI Listing
May 2021

The efficacy and risk factors of mechanical thrombectomy for the treatment of vertebrobasilar artery occlusion: a single center study.

Ann Palliat Med 2021 Apr;10(4):4697-4704

Department of Neurology, Taixing People's Hospital, Taixing, China.

Background: The mortality of acute ischemic stroke patients caused by vertebrobasilar artery occlusion (VBAO) is high and mechanical thrombectomy has gradually become a promising treatment for acute ischemic stroke. This study analyzed the efficacy of mechanical thrombectomy and the risk factors associated with poor outcomes in VBAO patients caused by severe local atherosclerotic stenosis.

Methods: This retrospective study enrolled patients with acute ischemic stroke caused by VBAO between March 1, 2016 and August 31, 2019. Patient demographic and clinical data were collected retrospectively. All enrolled patients were retrospectively interviewed for at least 3 months. Patients with a modified Rankin scale (mRS) score between 0 and 3 points were defined as having satisfactory outcomes while those with more than 3 points were defined as having unsatisfactory outcomes. In-hospital mortality, the rates of recanalization, and the rates of intracerebral hemorrhage were also recorded. Multivariable logistic regression was used to determine the risk factors of unsatisfactory outcomes in enrolled patients.

Results: A total of 65 patients were enrolled in this study with a median age 69.0 (63.0-78.0) years and 48 patients (73.8%) were male. Approximately 50% of patients had a mRS score of 0 or 1 point within 90 days after treatment with mechanical thrombectomy and 14 patients had a mRS score of 6 points. A total of 11 patients died in hospital. Out of the 65 patients, 7 required recanalization and 9 patients suffered from intracerebral hemorrhage. Multivariate logistic regression analysis showed that older age, lower baseline posterior circulation acute stroke prognosis early CT score (pcASPECTS), higher baseline National Institutes of Health stroke scale (NIHSS) score, and residual stenosis were independent risk factors of both unsatisfactory outcomes and mortality of VBAO patients.

Conclusions: This study confirmed the important role of mechanical thrombectomy in the treatment of acute ischemic stroke caused by VBAO and may provide some guidance for improving the prognosis of patients.
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http://dx.doi.org/10.21037/apm-21-614DOI Listing
April 2021

miR-21 in EVs from pulmonary epithelial cells promotes myofibroblast differentiation via glycolysis in arsenic-induced pulmonary fibrosis.

Environ Pollut 2021 Apr 29;286:117259. Epub 2021 Apr 29.

Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; China International Cooperation Center for Environment and Human Health, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. Electronic address:

As an environmental toxicant, arsenic causes damage to various organs and systems of the body and has attracted worldwide attention. It is well-known that exposure to arsenic can induce pulmonary fibrosis, but the molecular mechanisms are elusive. Glycolysis is involved in the process of various diseases, including pulmonary fibrosis. Extracellular vehicles (EVs) are mediators of cell communication through transporting miRNAs. The potential of miRNAs in EVs as liquid biopsy biomarkers for various diseases has been reported, and they have been applied in clinical diagnoses. In the present investigation, we focused on the roles and mechanisms of miR-21 in EVs on arsenic-induced glycolysis and pulmonary fibrosis through experiments with human populations, experimental animals, and cells. The results for arsenicosis populations showed that the serum levels of hydroxyproline, lactate, and EVs-miRNAs were elevated and that EVs-miR-21 levels were positively related to the levels of hydroxyproline and lactate. For mice, chronic exposure to arsenite led to high levels of miR-21, AKT activation, elevated glycolysis, and pulmonary fibrosis; however, these effects were blocked by the depletion of miR-21 in miR-21 knockout (miR-21) mice. After MRC-5 cells were co-cultured with arsenite-treated HBE cells, the levels of miR-21, AKT activation, glycolysis, and myofibroblast differentiation were enhanced, effects that were blocked by reducing miR-21 and by inhibiting the EVs in HBE cells. The down-regulation of PTEN in MRC-5 cells and primary lung fibroblasts (PLFs) reversed the blocking effect of inhibiting miR-21 in HBE cells. Thus, miR-21 down-regulates PTEN and promotes glycolysis via activating AKT, which is associated with arsenite-induced myofibroblast differentiation and pulmonary fibrosis. Our results provide a new approach for the construction of clinical diagnosis technology based on analysis of the mechanism of arsenite-induced pulmonary fibrosis.
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http://dx.doi.org/10.1016/j.envpol.2021.117259DOI Listing
April 2021

Cotton DMP gene family: Characterization, evolution, and expression profiles during development and stress.

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

State Key Laboratory of Cotton Biology, Institute of Cotton Research, Chinese Academy of Agricultural Sciences, Anyang 455000, Henan, China. Electronic address:

Members of DOMAIN OF UNKNOWN FUNCTION 679 membrane protein (DMP) gene family, a type of plant-specific membrane proteins, have been proposed to function in various physiological processes such as reproductive development and senescence in plants. Here, a total of 174 DMP genes were identified and analyzed in 16 plant species (including 58 DMPs in four cotton species). Phylogenetic analysis showed that these DMPs could be clustered into five subfamilies (I-V). 137 duplicated cotton gene pairs were identified and most duplicate events were formed by whole-genome duplication (WGD)/segmental duplications. Expression analysis revealed that most of cotton DMPs were mainly expressed in the reproductive organs (the sepal, petal, pistil and anther) and the fiber of secondary cell wall stage. GhDMPs promoter regions containing the different cis-elements also showed different responses to abiotic stress. In addition, gene interaction networks showed that DMPs, as an endomembrane system, were involved in plant senescence process and flower reproductive development. We speculated GhDMP8-A/-D, GbDMP8-A/-D could be used as some candidate gene for inducing cotton haploid. This genome-wide study provides a systematic analysis of the cotton DMP gene family, and further insights towards understanding the potential functions of candidate genes.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.023DOI Listing
May 2021

Detection of k-complexes in EEG signals using a multi-domain feature extraction coupled with a least square support vector machine classifier.

Neurosci Res 2021 May 6. Epub 2021 May 6.

School of Electrical and Electronic Engineering, Hubei University of Technology, Wuhan, China.

Sleep scoring is one of the primary tasks for the classification of sleep stages using electroencephalogram (EEG) signals. It is one of the most important diagnostic methods in sleep research and must be carried out with a high degree of accuracy because any errors in the scoring in the patient's sleep EEG recordings can cause serious problems. The aim of this research is to develop a new automatic method for detecting the most important characteristics in sleep stage 2 such as k-complexes based on multi-domain features. In this study, each EEG signal is divided into a set of segments using a sliding window technique. Based on extensive experiments during the training phase, the size of the sliding window is set to 0.5 seconds (s). Then a set of statistical, fractal, frequency and non-linear features are extracted from each epoch based on the time domain, Katz's algorithm, power spectrum density (PSD) and tunable Q-factor wavelet transform (TQWT). As a result, a vector of twenty-two features is obtained to represent each EEG segment. In order to detect k-complexes, the extracted features were analysed for their ability to detect the k-complex waveforms. Based on the analysis of the features, twelve out of twenty-two features are selected and forwarded to a least square support vector machine (LS-SVM) classifier to identify k-complexes in EEG signals. A set of various classification techniques of K-means and extreme learning machine classifiers are used to compare the obtained results and to evaluate the performance of the proposed method.The experimental results showed that the proposed method, based on multi-domain features, achieved better recognition results than other methods and classifiers. An average accuracy, sensitivity and specificity of 97.7%, 97%, and 94.2% were obtained, respectively, with the CZ-A1 channel according to the R&K standard. The experimental results with high classification performance demonstrated that the technique can help doctors optimize the diagnosis and treatment of sleep disorders.
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http://dx.doi.org/10.1016/j.neures.2021.03.012DOI Listing
May 2021

Electrospun fibrous sponge via short fiber for mimicking 3D ECM.

J Nanobiotechnology 2021 May 8;19(1):131. Epub 2021 May 8.

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, People's Republic of China.

Background: Most of the natural extracellular matrix (ECM) is a three-dimensional (3D) network structure of micro/nanofibers for cell adhesion and growth of 3D. Electrospun fibers distinctive mimicked 2D ECM, however, it is impossible to simulate 3D ECM because of longitudinal collapse of continuous micro/nanofibers. Herein, 3D electrospun micro/nano-fibrous sponge was fabricated via electrospinning, homogenization, shaping and thermal crosslinking for 3D tissue regeneration of cells and vascular.

Results: Fibrous sponge exhibited high porosity, water absorption and compression resilience and no chemical crosslinked agent was used in preparation process. In vitro studies showed that the 3D short fiber sponge provided an oxygen-rich environment for cell growth, which was conducive to the 3D proliferation and growth of HUVECs, stimulated the expression of VEGF, and well promoted the vascularization of HUVECs. In vivo studies showed that the 3D short fiber sponges had a good 3D adhesion to the chronic wound of diabetes in rats. Furthermore, 3D short fibrous sponges were better than 2D micro/nanofiber membranes in promoting the repair of diabetic full-thickness skin defects including wound healing, hair follicle regeneration, angiogenesis, collagen secretion.

Conclusion: Therefore, electrospun short fibrous sponges are special candidates for mimicking the 3D ECM and promoting 3D regeneration of tissue.
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http://dx.doi.org/10.1186/s12951-021-00878-5DOI Listing
May 2021

Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals.

Nat Commun 2021 May 7;12(1):2563. Epub 2021 May 7.

National Centre for Gene Research, CAS-JIC Centre of Excellence for Plant and Microbial Science (CEPAMS), Centre of Excellence for Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat-the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a 'self-poisoning' scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.
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http://dx.doi.org/10.1038/s41467-021-22920-8DOI Listing
May 2021

Role of innate immunity in chemotherapy-induced peripheral neuropathy.

Neurosci Lett 2021 May 4;755:135941. Epub 2021 May 4.

The Department of Pain Medicine Research, The Division of Anesthesiology, Critical Care and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, United States. Electronic address:

It has become increasingly clear that the innate immune system plays an essential role in the generation of many types of neuropathic pain including that which accompanies cancer treatment. In this article we review current findings of the role of the innate immune system in contributing to cancer treatment pain at the distal endings of peripheral nerve, in the nerve trunk, in the dorsal root ganglion and in the spinal dorsal horn.
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http://dx.doi.org/10.1016/j.neulet.2021.135941DOI Listing
May 2021

Optimization, and and evaluation of etomidate intravenous lipid emulsion.

Drug Deliv 2021 Dec;28(1):873-883

School of Pharmacy, North China University of Science and Technology, Tangshan, China.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties and . Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.
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http://dx.doi.org/10.1080/10717544.2021.1917729DOI Listing
December 2021

Transformation pathway from CdSe magic-size clusters with absorption doublets at 373/393 nm to clusters at 434/460 nm.

Angew Chem Int Ed Engl 2021 May 6. Epub 2021 May 6.

Sichuan University Engineering Research Center in Biomaterials: National Engineering Research Center for Biomaterials, No. 24, South Section, First Ring Road, Chengdu, 610065, Chengdu, CHINA.

Divergent interpretations have appeared in the literature regarding the structural nature and evolutionary behavior for photoluminescent CdSe nano-species with sharp doublets in optical absorption. Here, we report a comprehensive description of the transformation pathway from one CdSe nano-species displaying an absorption doublet at 373/393 nm to another species with a doublet at 433/460 nm. These two nano-species are shown to be as zero-dimension (0D) magic-size clusters (MSCs) with 3D quantum confinement, and are labelled dMSC-393 and dMSC-460, respectively. Synchrotron-based small angle X-ray scattering (SAXS) returns a radius of gyration of 0.92 nm for dMSC-393 and 1.14 nm for dMSC-460, and indicates that both types are disc-shaped with the exponent of the SAXS form factor equal to 2.1. The MSCs develop from their unique counterpart precursor compounds (PCs), which are labelled PC-393 and PC-460, respectively. For the dMSC-393 to dMSC-460 transformation, the proposed PC-enabled pathway is comprised of three key steps, dMSC-393 to PC-393 (Step 1), PC-393 to PC-460 (Step 2 involving monomer addition), and PC-460 to dMSC-460 (Step 3). The present study provides a framework for understanding the PC-based evolution of MSCs and how PCs enable transformations between MSCs.
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http://dx.doi.org/10.1002/anie.202104986DOI Listing
May 2021

Comparison of Clinical Outcomes Between Second-and First-Generation Drug-Eluting Stents in Patients With Chronic Total Occlusion Lesion: A Meta-Analysis.

Front Cardiovasc Med 2021 20;8:598046. Epub 2021 Apr 20.

Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, China.

The second-generation drug-eluting stents have been used to treat chronic total occlusion lesion. However, there is limited evidence of the clinical outcomes that whether the second-generation drug-eluting stents is superior to first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The study aimed to compare the differences in clinical outcomes between the two generations drug-eluting stents in patients with those by a meta-analysis. PubMed, Embase, the Cochrane library and Web of science databases were systemically searched before March, 2021. Randomized controlled trials and observational studies were included to compare the second-generation drug-eluting stents with the first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The clinical outcomes were major adverse cardiac events (MACE), target vessel revascularization, myocardial infarction, all-cause death. Fixed effects models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of each clinical outcome. Sensitivity analysis was performed to detect potential sources of heterogeneity. Subgroup analyses were used to assess the differential effects. The meta-analysis included eight studies involving 4,583 patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. Pooled analysis showed that the incidence of MACE (OR = 0.68, 95%CI 0.54-0.85, = 0.0008), target vessel revascularization (OR = 0.70, 95%CI 0.54-0.91, = 0.007), and myocardial infarction (OR = 0.58, 95%CI 0.37-0.93, = 0.02) were lower in the second-generation drug-eluting stents compared with the first-generation ones. However, there was not difference in all-cause deaths between two drug-eluting stents (OR = 0.67, 95%CI 0.45-1.01, = 0.05). The second-generation drug-eluting stents are associated with lower MACE, target vessel revascularization, and myocardial infarction compared with the first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The results of this study can provide a reference for the selection of stents in patients with chronic total occlusion lesion. Further randomized controlled trials are needed to verify that the second-generation drug-eluting stents is superior to the first-generation ones in patients with chronic total occlusion (Registered by PROSPERO, CRD42020158406).
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http://dx.doi.org/10.3389/fcvm.2021.598046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096061PMC
April 2021

Population Pharmacokinetics of CC-122.

Clin Pharmacol 2021 28;13:61-71. Epub 2021 Apr 28.

Clinical Pharmacology & Pharmacometrics, Bristol Myers Squibb, Summit, NJ, USA.

Background: CC-122 is a cereblon-modulating agent that exerts direct cell-autonomous activity against malignant B cells and immunomodulatory effects. Herein, a population pharmacokinetic (popPK) model of CC-122 was developed and the influence of demographic and disease-related covariates on population pharmacokinetic parameters was assessed based on data from three clinical studies of CC-122 (dose range, 0.5-15 mg) in healthy subjects and cancer patients.

Methods: Nonlinear mixed effects modeling was employed in developing a population pharmacokinetic model of CC-122 based on 298 patients from 3 clinical studies.

Results: The PK of CC-122 was adequately described with a two-compartment model with first-order absorption and elimination. Tumor types were found to be significantly correlated with apparent clearance (CL/F) and apparent volume of distribution of the central compartment. Creatinine clearance was identified as a statistically significant covariate of CL/F. Sex and body weight were statistically but not clinically relevant on V2/F.

Conclusion: In conclusion, the two-compartment model built can be used to adequately describe the time course of the population pharmacokinetics of CC-122 and should serve as the basis for dose adjustment decision-making of CC-122.
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http://dx.doi.org/10.2147/CPAA.S310604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093142PMC
April 2021

MiR-34a suppression targets Nampt to ameliorate bone marrow mesenchymal stem cell senescence by regulating NAD-Sirt1 pathway.

Stem Cell Res Ther 2021 May 6;12(1):271. Epub 2021 May 6.

The Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xin Min Street, Changchun, Jilin Province, People's Republic of China.

Background: Expansion-mediated replicative senescence and age-related natural senescence have adverse effects on mesenchymal stem cell (MSC) regenerative capability and functionality, thus severely impairing the extensive applications of MSC-based therapies. Emerging evidences suggest that microRNA-34a (miR-34a) has been implicated in the process of MSC senescence; however, the molecular mechanisms with regard to how miR-34a influencing MSC senescence remain largely undetermined.

Methods: MiR-34a expression in MSCs was evaluated utilizing RT-qPCR. The functional effects of miR-34a exerting on MSC senescence were investigated via gene manipulation. Relevant gene and protein expression levels were analyzed by RT-qPCR and western blot. Luciferase reporter assays were applied to confirm that Nampt is a direct target of miR-34a. The underlying regulatory mechanism of miR-34a targeting Nampt in MSC senescence was further explored by measuring intracellular NAD content, NAD/NADH ratio and Sirt1 activity.

Results: In contrast to Nampt expression, miR-34a expression incremented in senescent MSCs. MiR-34a overexpression in young MSCs resulted in senescence-associated characteristics as displayed by senescence-like morphology, prolonged cell proliferation, declined osteogenic differentiation potency, heightened senescence-associated-β-galactosidase activity, and upregulated expression levels of the senescence-associated factors. Conversely, miR-34a suppression in replicative senescent and natural senescent MSCs contributed to diminished senescence-related phenotypic features. We identified Nampt as a direct target gene of miR-34a. In addition, miR-34a repletion resulted in prominent reductions in Nampt expression levels, NAD content, NAD/NADH ratio, and Sirt1 activity, whereas anti-miR-34a treatment exerted the opposite effects. Furthermore, miR-34a-mediated MSC senescence was evidently rescued following the co-treatment with Nampt overexpression.

Conclusion: This study identifies a significant role of miR-34a playing in MSC replicative senescence and natural senescence via targeting Nampt and further mediating by NAD-Sirt1 pathway, carrying great implications for optimal strategies for MSC therapeutic applications.
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http://dx.doi.org/10.1186/s13287-021-02339-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101138PMC
May 2021

Prenatal exposure to propylparaben at human-relevant doses accelerates ovarian aging in adult mice.

Environ Pollut 2021 Apr 28;285:117254. Epub 2021 Apr 28.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, Hubei, China. Electronic address:

Embryonic exposure to environmental chemicals may result in specific chronic diseases in adulthood. Parabens, a type of environmental endocrine disruptors widely used in pharmaceuticals and cosmetics, have been shown to cause a decline in women's reproductive function. However, whether exposure to parabens during pregnancy also negatively affect the ovarian function of the female offspring in adulthood remains unclear. This study aims to investigate the effects of prenatal propylparaben (PrP) exposure on the ovarian function of adult mice aged 46 weeks, which is equivalent to the age of 40 years in women. Pregnant ICR mice were intraperitoneally injected with human-relevant doses of PrP (i.e., 0, 7.5, 90, and 450 mg/kg/day) during the fetal sex determination period-from embryonic day E7.5 to E13.5. Our results revealed that ovarian aging was accelerated in PrP-exposed mice at 46 weeks, with altered regularity of the estrous cycle, decreased serum estrogen (E2) and progesterone (P4) levels, reduced size of the primordial follicle pool, and increased number of atretic follicles. It was found that prenatal exposure to human-relevant doses of PrP exacerbated ovarian oxidative stress, inflammation, and fibrosis, which promoted follicular atresia by activating the mitochondrial apoptosis pathway. To compensate, the depletion of primordial follicles was also accelerated by activating the PI3K/AKT/mTOR signaling pathway in PrP-exposed mice. Moreover, PrP induced hypermethylation of CpG sites in the promoter region of Cyp11a1 (a 17.16-64.28% increase) partly led to the disrupted steroidogenesis, and the altered methylation levels of imprinted genes H19 and Peg3 may also contribute to the phenotypes observed. These remarkable findings highlight the embryonic origin of ovarian aging and suggest that a reduced use of PrP during pregnancy should be advocated.
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http://dx.doi.org/10.1016/j.envpol.2021.117254DOI Listing
April 2021

Percutaneous gastrostomy compared with esophageal stenting for the treatment of esophageal cancer with dysphagia.

J Vasc Interv Radiol 2021 May 3. Epub 2021 May 3.

Minimally Invasive and Interventional Department, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan, China. Electronic address:

Purpose: To compare the outcomes of self-expandable metal stent and percutaneous gastrostomy (PG) for treatment of patients with esophageal cancer (EC) and dysphagia.

Materials And Methods: This retrospective observational study consisted of 113 patients with EC and dysphagia who underwent either stent insertion (n = 47) or PG (n = 66) at a single center between June 2014 and June 2018.

Results: There were 63 men and 50 women with the mean age of 76.5 ± 4.9 years. The two groups had similar baseline characteristics, except that the PG group had a higher percentage of patients with cervical EC (22.7%. vs 2.1%, P < 0.001). The PG group had better maintenance of nutritional status in terms of reduction of serum albumin level (P = 0.039) and weight loss (P = 0.041). Compared with the stent group, the PG group demonstrated a lower incidence of local severe pain (0% vs 21.3%, P < 0.001), and lower incidence of dislodgment of device (1.5% vs 19.1%, P = 0.002). The PG group demonstrated longer overall survival than the stent group, for stages II and III (201 vs 185 days, P = 0.034) and stage IV (122 vs 86 days, P = 0.001).

Conclusion: Compared with stent insertion, PG is associated with better maintenance of nutritional status, fewer complications, and better survival. Thus, PG may be the preferred choice for treating malnutrition in patients with EC and dysphagia.
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http://dx.doi.org/10.1016/j.jvir.2021.04.019DOI Listing
May 2021

Resilience function uncovers the critical transitions in cancer initiation.

Brief Bioinform 2021 May 5. Epub 2021 May 5.

School of Automation, Northwestern Polytechnical University, No.127, Youyi West Road, Xi'an 710072, China.

Considerable evidence suggests that during the progression of cancer initiation, the state transition from wellness to disease is not necessarily smooth but manifests switch-like nonlinear behaviors, preventing the cancer prediction and early interventional therapy for patients. Understanding the mechanism of such wellness-to-disease transitions is a fundamental and challenging task. Despite the advances in flux theory of nonequilibrium dynamics and 'critical slowing down'-based system resilience theory, a system-level approach still lacks to fully describe this state transition. Here, we present a novel framework (called bioRFR) to quantify such wellness-to-disease transition during cancer initiation through uncovering the biological system's resilience function from gene expression data. We used bioRFR to reconstruct the biologically and dynamically significant resilience functions for cancer initiation processes (e.g. BRCA, LUSC and LUAD). The resilience functions display the similar resilience pattern with hysteresis feature but different numbers of tipping points, which implies that once the cell become cancerous, it is very difficult or even impossible to reverse to the normal state. More importantly, bioRFR can measure the severe degree of cancer patients and identify the personalized key genes that are associated with the individual system's state transition from normal to tumor in resilience perspective, indicating that bioRFR can contribute to personalized medicine and targeted cancer therapy.
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http://dx.doi.org/10.1093/bib/bbab175DOI Listing
May 2021

Efficacy and Safety of Qingpeng Ointment for Subacute and Chronic Eczema: A Systematic Review and Meta-Analysis.

Biomed Res Int 2021 15;2021:5594953. Epub 2021 Apr 15.

Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Objective: To evaluate the efficacy and safety of Qingpeng ointment for the treatment of subacute and chronic eczema.

Method: Randomized controlled trials (RCTs) on Qingpeng ointment for subacute and chronic eczema were searched on PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Science and Technology Periodical Journal from their inception to 30 November 2020. Quality assessment and data analysis were performed by Review Manager 5.3.

Results: A total of 26 RCTs were included. Qingpeng ointment could significantly improve the total efficacy rate (TER) (RR = 2.60, 95% CI: 2.11 to 3.21, < 0.00001), reduce the total symptom score (TSS) (SMD = -2.35, 95% CI: -3.74 to -0.97, = 0.0009), and decrease visual analogue scale (VAS) for pruritus (MD = -3.86, 95% CI: -4.41 to -3.31, < 0.00001) compared with the placebo. The TER of Qingpeng ointment was similar to that of topical corticosteroid (TCS) (RR = 0.96, 95% CI: 0.88 to 1.03, = 0.25), and the TSSs between Qingpeng ointment and medium or low potency TCS were not significantly different (SMD = -0.05, 95% CI: -0.22 to 0.12, = 0.54). However, Qingpeng ointment was not superior to TCS in reducing VAS score (SMD = 0.48, 95% CI: 0.00 to 0.96, = 0.05). In addition, Qingpeng ointment combined with TCS performed better than TCS alone in all three outcomes. For safety, nothing but skin irritative reactions occurred in the Qingpeng ointment group, and its incidence of skin irritative reactions was similar to those of the placebo (RR = 1.47, 95% CI: 0.61 to 3.55, = 0.40) and TCS (RR = 1.82, 95% CI: 0.79 to 4.22, = 0.16). The combined therapy did not increase the risk of skin irritative reactions (RR = 0.69, 95% CI: 0.27 to 1.78, = 0.44).

Conclusion: Qingpeng ointment is an effective and safe treatment for subacute and chronic eczema. It is also an add-on treatment to TCS for eczema. However, due to the suboptimal quality of the included studies, more large-sample and high-quality RCTs are needed to improve the evidence quality.
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http://dx.doi.org/10.1155/2021/5594953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064792PMC
April 2021

Different Metabolites in the Roots, Seeds, and Leaves of and Their Role in Alleviating Oxidative Stress.

J Anal Methods Chem 2021 15;2021:6628880. Epub 2021 Apr 15.

State Key Laboratory of Innovative Drug and Efficient Energy-Saving Pharmaceutical Equipment, Nanchang 330006, China.

In this study, we examined the metabolites from different parts of and their role in alleviating damage caused by oxidative stress. We used UHPLC-QTOF-MS to analyze the chemical components in the root, seed, and leaf extracts of . Two multivariate statistical analysis methods-namely, principal component analysis and partial least square discriminant analysis-were used to distinguish the samples obtained from different parts of the plant. Using univariate statistics, 130 different metabolites were screened out. Among these, the relative content of flavonoids and terpenoids was found to be highest in the leaves, the lignin and phenolic acid content was highest in the roots, and the amino acid and phenolic acid levels were highest in seeds. An MTT assay was used to test the anti-HO oxidative damage to PC12 cells in different parts of the sample. Lastly, using Pearson's correlation analysis, various metabolites from different parts of were correlated with their antioxidant effects from the corresponding parts. Fifty-two related different metabolites were found, of which 20 metabolites that were positively correlated to oxidative stress were present at a relatively higher level in the roots, whereas 32 metabolites that were negatively correlated were present at relatively higher levels in the seeds and leaves. The results of this study reveal the distribution characteristics and the antioxidant activity of different metabolites of and provide a reference for the rational development of its medicinal parts.
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http://dx.doi.org/10.1155/2021/6628880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064801PMC
April 2021

Extremity Gangrene Caused by HBV-Related Cryoglobulinemia Vasculitis in a Patient with Diabetes - A Case Report.

J Inflamm Res 2021 28;14:1661-1666. Epub 2021 Apr 28.

Diabetic Foot Care Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

We presented a case of hepatitis B virus (HBV)-related type III cryoglobulinemia vasculitis (CryoVas) characterized by extremity gangrene in a patient with diabetes. The 60-year-old female had a 10-year history of poorly controlled type 2 diabetes mellitus. She complained of sudden onset pain and swelling of toes which quickly progressed to gangrene, with fingers becoming pain and dark violet. The patient was initially misdiagnosed as diabetic foot (DF). Although DF is one of the common chronic complications of diabetes, it rarely involves the hand. What is more, the ischemic manifestations of the extremity were not consistent with the results of the vascular examination and immune system changes. The patient had Raynaud's phenomenon, arthralgia, and extremity gangrene. Test results showed cryoglobulinemia multiple positive, polyclonal immunoglobulin with rheumatoid factor negative, lower complement 3, leukocytoclastic vasculitis, and HBV infection. HBV-related type III CryoVas was finally diagnosed, and a conservative therapy strategy was given. Six months after treatment with cyclophosphamide, corticosteroid, nucleoside/nucleotide analog therapy, local debridement, and dressing change, she recovered and kept no recurrence by following up for 30 months. To our knowledge, this is the first report of extremity gangrene caused by HBV-related CryoVas in a diabetic patient.
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http://dx.doi.org/10.2147/JIR.S308687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092113PMC
April 2021

Stimulation of α7-nAChRs coordinates autophagy and apoptosis signaling in experimental knee osteoarthritis.

Cell Death Dis 2021 May 5;12(5):448. Epub 2021 May 5.

Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, China.

Osteoarthritis (OA) is the most common chronic joint disease in the elderly population. Growing evidence indicates that a balance between autophagy and apoptosis in chondrocytes plays a key role in OA's cartilage degradation. Thus, drugs targeting the balance between apoptosis and autophagy are potential therapeutic approaches for OA treatment. In previous studies, we found that the activation of α7 nicotinic acetylcholine receptors (α7-nAChRs) alleviated monosodium iodoacetate (MIA)-induced joint degradation and osteoarthritis pain. To explore the potential functions of α7-nAChRs in autophagy and apoptosis signaling in knee OA, we compared the expression of α7-nAChRs in human knee articular cartilage tissues from normal humans and OA patients. We found that knee joint cartilage tissues of OA patients showed decreased α7-nAChRs and an imbalance between autophagy and apoptosis. Next, we observed that α7-nAChRs deficiency did not affect cartilage degradation in OA development but reversed the beneficial effects of nicotine on mechanical allodynia, cartilage degradation, and an MIA-induced switch from autophagy to apoptosis. Unlike in vivo studies, we found that primary chondrocytes from α7-nAChRs knockout (KO) mice showed decreased LC3 levels under normal conditions and were more sensitive toward MIA-induced apoptosis. Finally, we found that α7-nAChRs deficiency increased the phosphorylation of mTOR after MIA treatment, which can also be observed in OA patients' tissues. Thus, our findings not only confirmed that nicotine alleviated MIA-induced pain behavior and cartilage degradation via stimulating the α7-nAChRs/mTOR signal pathway but found the potential role of α7-nAChRs in mediating the balance between apoptosis and autophagy.
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http://dx.doi.org/10.1038/s41419-021-03726-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100296PMC
May 2021

Sustained delivery of MMP-9 siRNA via thermosensitive hydrogel accelerates diabetic wound healing.

J Nanobiotechnology 2021 May 5;19(1):130. Epub 2021 May 5.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, P. R. China.

Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.
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http://dx.doi.org/10.1186/s12951-021-00869-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097905PMC
May 2021