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☐ ☆ ✇ BMJ Open

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II)

Por: Zhang · J. · Hu · X. · Jiang · J. · Lu · D. · Guo · L. · Peng · X. · Pan · Y. · He · W. · Li · J. · Zhou · H. · Huang · J. · Jiang · F. · Pu · J. · Cheng · Z. · Yang · B. · Ma · J. · Chen · P. · Liu · Q. · Song · D. · Lu · L. · Li · S. · Fan · Y. · Meng · Z. · Tang · L. · Shin · E.-S. · Tu · S. · Koo · B.- — Diciembre 10th 2023 at 15:59
Introduction

Percutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses, FFR resulted in fewer coronary interventions and was non-inferior to IVUS with respect to clinical outcomes. However, whether this finding can be applied to angiography-derived FFR in significant coronary artery disease (CAD) remains unclear.

Method and analysis

The comparison of angiography-derived FFR-guided and IVUS-guided intervention strategies for clinical outcomes in patients with coronary artery disease (FLAVOUR II) trial is a multicentre, prospective, randomised controlled trial. A total of 1872 patients with angiographically significant CAD (stenoses of at least 50% as estimated visually through angiography) in a major epicardial coronary artery will be randomised 1:1 to receive either angiography-derived FFR-guided or IVUS-guided PCI. Patients will be treated with second-generation drug-eluting stent according to the predefined criteria for revascularisation: angiography-derived FFR≤0.8 and minimal lumen area (MLA)≤3 mm2 or 3 mm22 and plaque burden>70%. The primary endpoint is a composite of all-cause death, myocardial infarction and revascularisation at 12 months after randomisation. We will test the non-inferiority of the angiography-derived FFR-guided strategy compared with the IVUS-guided decision for PCI and the stent optimisation strategy.

The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD.

Ethics and dissemination

FLAVOUR II was approved by the institutional review board at each participating site (The Second Affiliated Hospital of Zhejiang University School of Medicine Approval No: 2020LSYD410) and will be conducted in line with the Declaration of Helsinki. Informed consent would be obtained from each patient before their participation. The study results will be submitted to a scientific journal.

Trial registration number

NCT04397211.

☐ ☆ ✇ BMJ Open

Effects of the different intensities of task-oriented training on the upper extremity motor function and self-care ability of stroke survivors: study protocol for a multiarm parallel-group randomised controlled trial in a tertiary hospital in China

Por: Liu · S. · Zhang · K. · Li · X. · Li · C. · Peng · M. — Diciembre 9th 2023 at 17:51
Introduction

Although task-oriented training (TOT) may provide added therapeutic value to stroke survivors, current TOT guidance offers insufficient advice on standardisation, particularly choices of intensity, for clinical practice. Therefore, this study aims to explore the effects of different intensities of TOT on motor function and self-care ability of stroke survivors.

Methods and analysis

This randomised controlled clinical trial will recruit 72 participants from a tertiary hospital, diagnosed with decreased self-care ability and upper limb motor dysfunction post-stroke. All participants will be randomly assigned to one of three experimental groups or the control group to undergo intervention for 8 weeks. The participants in the control group (n=18) will receive traditional occupational therapy, while those in the experimental groups will receive different intensities of TOT (50%, 75% and 100% intensity for groups A, B and C, respectively). This protocol designed a more innovative and optimised TOT programme to explore the optimal intensity of TOT on stroke survivors. The primary outcome is Canadian Occupational Performance Measure, and the secondary outcomes include Modified Barthel Index, Wolf Motor Function Test and Motor Activity Log.

Ethics and dissemination

The Second Affiliated Hospital of Hainan Medical University Ethics Committee approved the medical and ethical protocol for this study (LW2022015). All participants will sign an informed consent form. The results will be presented in scientific conferences and published in peer-reviewed journals.

Trial registration number

ChiCTR2200056390.

☐ ☆ ✇ BMJ Open

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial

Por: Li · G. · Sun · Y. · Liu · T. · Yang · P. · Peng · Y. · Chen · W. · Zhang · L. · Chu · J. · Kuai · D. · Wang · Z. · Wu · W. · Xu · Y. · Zhou · B. · Geng · Y. · Yin · C. · Li · J. · Wang · M. · Peng · X. · Xiao · Y. · Li · M. · Zhang · X. · Liu · P. · Wang · N. · Zhang · Y. — Diciembre 9th 2023 at 17:51
Objectives

This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation.

Setting and participants

This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18–80 years with LVO in anterior circulation.

Interventions

Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis.

Primary and secondary outcome measures

The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the 2 test or Fisher’s exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach.

Results

Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass.

Conclusions

Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy.

Trial registration number

NCT04995757.

☐ ☆ ✇ BMJ Open

Experiences and management needs of endocrine therapy-related symptoms in patients with breast cancer: a systematic review and qualitative evidence synthesis protocol

Por: Wang · L. · Wei · T. · Liu · J. · Peng · S. · Chen · J. · Hu · M. · Li · X. — Diciembre 7th 2023 at 23:50
Introduction

Patients with breast cancer and endocrine therapy-related symptoms often experience pain, self-denial, anxiety, fear of recurrence and despair, which can be extremely physically and psychologically traumatising for the patients. Failure to receive effective support and management reduces adherence to medications, leading to a higher risk of relapse and mortality. Clearly, it is paramount to identify what support these patients may need and how to meet their symptom management needs. This paper outlines a protocol to synthesise qualitative evidence on endocrine therapy symptom experiences, management expectations and preferences of patients with breast cancer.

Methods and analysis

The following databases were searched in November 2023 with no date restriction applied: The Cochrane Library, PubMed, Embase, Web of Science, Scopus, CINAHL and OpenGrey. Published studies on qualitative or mixed-method on symptom experiences and management needs during endocrine therapy in patients with breast cancer will be retrieved. We will also search for reference lists and perform a forward citation search. Before inclusion in this review, two reviewers will independently apply the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research to ensure methodological validity. Any disagreements regarding the evaluation of the articles will be resolved through discussion with or by a third reviewer. Data will be extracted using the standardised data extraction tool EndNote20 for unified management, assessment, and review of information. The common sense model of self-regulation will guide data extraction and synthesis. The final synthesised findings will be graded according to the GRADE-CERQual approach to establish confidence.

Ethics and dissemination

This systematic review addressed previously published studies without personally identifiable participant information. Ethical approval from the research committee was not required. The findings of this systematic review will be disseminated to various key stakeholders and published in peer-reviewed journals.

PROSPERO registration number

CRD42023406987

☐ ☆ ✇ PLOS ONE Medicine&Health

Polyethylene glycol precipitation is an efficient method to obtain extracellular vesicle-depleted fetal bovine serum

by Peng Wang, Onno J. Arntz, Johanna F. A. Husch, Van der Kraan P. M., Jeroen J. J. P. van den Beucken, Fons A. J. van de Loo

Mesenchymal stromal/stem cell derived-extracellular vesicles (MSC-EVs) have gained interest as drug delivery nanoparticles, having immunoregulatory and potentiating tissue repair property. To maintain growth of MSCs and obtain pure MSC-derived EVs, the culture media should contain fetal bovine serum (FBS) devoid of EVs, as the presence of FBS EVs confounds the properties of MSC-EVs. Therefore, we tested three methods: 18h ultracentrifugation (UC) and ultrafiltration (UF), which are common FBS EV depletion methods in current MSC-EV research, and polyethylene glycol (PEG) precipitation to obtain three EV depleted FBS (EVdFBS) batches, and compared them to FBS and commercial (Com) EVdFBS on human adipose stem cell (hADSC) growth, differentiation, enrichment of EVs in hADSC supernatant and their biological function on collagen metabolism. Our comparative study showed UC and UF vary in terms of depletion efficiency and do not completely deplete EVs and affects the growth-promoting quality of FBS. Specifically, FBS EV depletion was comparable between PEG (95.6%) and UF (96.6%) but less by UC (82%), as compared to FBS. FBS protein loss was markedly different among PEG (47%), UF (87%), and UC (51%), implying the ratio of EV depletion over protein loss was PEG (2.03), UF (1.11), and UC (1.61). A significant decrease of TGFβ/Smad signaling, involving in MSC growth and physiology, was observed by UF. After 96 hours of exposure to 5% FBS or 5% four different EVdFBS cell growth media, the osteogenesis ability of hADSCs was not impaired but slightly lower mRNA expression level of Col2a observed in EVdFBS media during chondrogenesis. In consistent with low confluency of hADSCs observed by optical microscope, cell proliferation in response to 5% UF EVdFBS media was inhibited significantly. Importantly, more and purer ADSCs EVs were obtained from ADSCs cultured in 5% PEG EVdFBS media, and they retained bioactive as they upregulated the expression of Col1a1, TIMP1 of human knee synovial fibroblast. Taken together, this study showed that PEG precipitation is the most efficient method to obtain EV depleted FBS for growth of MSCs, and to obtain MSC EVs with minimal FBS EV contamination.
☐ ☆ ✇ International Wound Journal

Effect of wound infiltration of dexmedetomidine in lumbar spine surgery on postoperative wound pain: A meta‐analysis

Por: Xiaoping Wang · Yao Peng · Yao Si · Xi Hu — Diciembre 5th 2023 at 09:29

Abstract

In a meta-study, we evaluated the effectiveness and security of the combination of topical anaesthetic and dexmedetomidine in the treatment of postoperative pain in patients with lumbar disease. Four databases were systematically searched for possible related articles. Only English-language research was taken into account on the Internet. Furthermore, we only took into account the studies that were published prior to 2023. Only those that fulfilled the eligibility criteria were considered: (1) in adults who were about to undergo spine operation, (2) dexmedetomidine combined with local anaesthesia, (3) Visual Analog Scale scores at 4 and 24 h after the event and (4) this was a randomized or nonrandomized, controlled study. The meta-analysis was carried out with Revman 5.3 software. A ROBINS-I-based instrument was used to evaluate controlled studies. All trials were synthesized by computing the end results with either a fixed or a random effect model, which was dependent on statistical diversity. Five trials showed a marked reduction in wound pain at 4 h after the operation in patients who were treated with dexmedetomidine for lumbar spinal surgery (MD, −0.81; 95% CI, −1.24, −0.35; p = 0.0005). In the case of lumbar spinal operations, the addition of dexmedetomidine to the postoperative treatment resulted in a marked reduction in the pain at 24 h post-operation (MD, −0.64; 95% CI, −0.79, −0.48; p < 0.0001). The quality of the data we evaluated was ‘moderate’ to ‘good’; thus, we have limited confidence in the impact estimation, and the actual impact might be significantly different from what we had expected. Additional studies should concentrate on practices that are well known to cause severe postoperative pain, especially for cases where the improvement of pain management may lead to substantial clinical benefits in terms of reduction of morbidity or cost-effectiveness in terms of quicker healing and release.

☐ ☆ ✇ International Wound Journal

Effects of Peripherally inserted Central Catheter (PICC) materials and designs on reduction of PICC‐related complications: A systematic review and meta‐analysis

Por: Nannan Ding · Huizhen Peng · Wenli Zhao · Yinping Yi · Yufeng Ma · Yaru Guo · Haiyun Li · Xue Wu — Diciembre 5th 2023 at 08:11

Abstract

Studies showed that integrating coating or valve into Peripherally Inserted Central (PICC) can prevent related complications. However, data regarding efficiency were controversial. Therefore, a systematic review was needed to analyse the effect of PICC materials and designs on reduction of PICC-related complications. We searched PubMed, Cochrane library, EMbase, grey literature and referent literature from inception to 5 August 2022. Randomized controlled trials (RCTs) and case–control study were included. Two authors extracted data independently, using a predesigned Excel form, and assessed the quality of included RCTs according to the Cochrane Handbook for Systematic Reviews (V5.1.0), case–control study was assessed by the Newcastle-Ottawa Scale. Data were analysed using Review Manager (v5.3.0). A total of 10 RCTs and one case–control study were included. Meta-analysis results showed that PICC designs reduce the incidence of obstruction, and at the critical value of PICC-associated bloodstream infection, but may have no effects on other complications. Based on the literature reviewed, we can only say PICC new materials did not reflect significant reduction on complications, what's more, the result needs more multicentre, large RCTs to support. We suggested clinicians combine descriptive research and cost-effect analysis to select appropriate PICC materials and designs for patients.

☐ ☆ ✇ International Wound Journal

Application of direct observation of operational skills in nursing skill evaluation of pressure injury: A randomized clinical trial

Por: Wei‐ying Zhang · Youqing Peng · Hui‐ren Zhuang · Hai‐ping Yu · Qin Liu · Yingjie Gu · Jiali Yao — Diciembre 5th 2023 at 08:10

Abstract

This was a non-blinded, single-centre, randomized, controlled clinical trial that compared the effectiveness of direct observation of procedural skills (DOPSs)with traditional assessment methods in pressure injury (PI) care skills. The study population included 82 nursing professionals randomly assigned to the study group (n = 41) and the control group (n = 41). Both groups of nurses underwent a 6-month training in PI care skills and were subsequently evaluated. The main outcome variables were the PI skill operation scores and theoretical scores. Secondary outcome variables included satisfaction and critical thinking abilities. Independent sample t-tests and chi-square tests were used to assess differences between the two groups of nurses. The results showed no statistically significant difference in PI skill operation scores between the two groups of nurses (p > 0.05). When comparing the PI theoretical scores, the study group scored higher than the control group, and this difference was statistically significant (p < 0.05). In terms of satisfaction assessment, the study group and the control group showed differences in improving self-directed learning, enhancing communication skills with patients, improving learning outcomes and increasing flexibility in clinical application (p < 0.05). When comparing critical thinking abilities between the two groups of nurses, there was no statistically significant difference at the beginning of the training, but after 3 months following the training, there was a statistically significant difference between the two groups (p < 0.01).The results indicated that the DOPS was effective in improving PI theoretical scores, increasing nurse satisfaction with the training and enhancing critical thinking abilities among nurses.

☐ ☆ ✇ PLOS ONE Medicine&Health

Effect of pueraria on left ventricular remodelling in HFrEF: A systematic review and meta-analysis

Por: Lipeng Shi · Lumei Huang · Erqian Yin · Jingwei Deng · Xuqin Du — Diciembre 4th 2023 at 15:00

by Lipeng Shi, Lumei Huang, Erqian Yin, Jingwei Deng, Xuqin Du

Background

Heart failure with reduced ejection fraction (HFrEF) is a prevalent cardiovascular disease globally, posing a significant burden on healthcare and society. Left ventricular remodelling is the primary pathology responsible for HFrEF development and progression, leading to increased morbidity and mortality. Pueraria, a traditional Chinese herbal medicine and food, is commonly used in China to treat HFrEF. Accumulating evidence suggests that pueraria can effectively reverse left ventricular remodelling in HFrEF patients. This meta-analysis aims to assess the impact of pueraria on left ventricular remodelling in HFrEF patients.

Methods

Eight electronic databases, including PubMed, EMBASE, Clinicaltrials.gov, Cochrane Library, Wanfang, CNKI, CQVIP, and CBM were searched for literature from inception to June 2023. All randomized controlled trials (RCTs) using pueraria in the treatment of HFrEF were included. The Cochrane Risk of Bias tool was utilized for RCTs’ methodological evaluation, while Review Manager 5.4.1 was used to analyze the data.

Results

Nineteen RCTs with a total of 1,911 patients (1,077 males and 834 females) were identified. Meta-analysis indicated that combination medication of pueraria and conventional medicine (CM) was superior to the CM alone in raising left ventricular ejection fraction (LVEF; MD = 6.46, 95% CI, 4.88 to 8.04, P CI, -6.55 to -3.01, P CI, -5.98 to -1.99, P CI, -185.30 to -67.03, P CI, 2.54 to 4.59, P CI, 41.77 to 89.31, P CI, 1.57 to 5.83, P = 0.0009). Regarding safety, no difference was observed for adverse events (RR = 0.59, 95% CI, 0.22 to 1.54, P = 0.28).

Conclusion

The use of pueraria combined with conventional medicine in HFrEF patients has superiority over conventional medicine alone in ameliorating cardiac function and reversing left ventricular remodeling. Moreover, combination medication has no increase in adverse drug events. Given some limitations, more prudence and high-quality clinical trials are needed in the future to verify the conclusions.

☐ ☆ ✇ Journal of Clinical Nursing

The incidence and risk factors of unplanned removal of peripherally inserted central catheters among adult patients: A multi‐centre cohort study

Por: Yan Liu · Xiaopeng Huo · Dingding Zhang · Yue Liu · Ruibin Ge · Jingyan Zhang · Weinan Liu · Yanping Shi · Kunrong Yu · Zhen Li · Wei Chen · Xinjuan Wu · Wenyan Sun — Diciembre 4th 2023 at 07:24

Abstract

Aims and Objectives

(i) To estimate the national incidence of unplanned removal of peripherally inserted central catheters (PICCs) in China. (ii) To explore the associated risk factors to provide evidence for the prevention.

Design

A multi-centre prospective cohort study.

Methods

A representative sample of 3222 Chinese adult patients with successful PICC insertion was recruited for the PICC Safety Management Research (PATH) using a two-stage cluster sampling method from December 2020 to June 2022. Sixty hospitals from seven Chinese provinces representing all geographical regions were selected. Demographic information and PICC characteristics were collected using a standard online case report form. Risk factors for the unplanned removal of PICCs were assessed using a cause-specific hazard model and verified using a sub-distribution hazard model. STROBE guidelines were followed in reporting this study.

Results

Three thousand one hundred and sixty-six patients were included in the final analysis with a mean age of 59 years and a total of 344,247 catheter days. The incidence of unplanned removal was 10.04%. Female, with thrombosis history, PICC insertion due to infusion failure, valved catheter and double-lumen catheter were risk factors, whereas longer insertion and exposure length were protective factors in the cause-specific hazard model. Higher BMI became an independent risk factor in the sub-distribution hazard model.

Conclusions

Unplanned removal of PICCs is a serious clinical challenge in China. Our findings call for prevention strategies targeting the identified risk factors.

Relevance to Clinical Practice

Our study characterised the epidemiology of unplanned removal of PICCs among Chinese adult inpatients, highlighting the need for prevention among this population and providing a basis for the formulation of relevant prevention strategies.

Patient or Public Contribution

Patients contributed through sharing their information required for the case report form. Healthcare professionals who provide direct care to the patient at each medical centre contributed by completing the online case report form.

☐ ☆ ✇ PLOS ONE Medicine&Health

Prime editing-mediated correction of the <i>CFTR</i> W1282X mutation in iPSCs and derived airway epithelial cells

by Chao Li, Zhong Liu, Justin Anderson, Zhongyu Liu, Liping Tang, Yao Li, Ning Peng, Jianguo Chen, Xueming Liu, Lianwu Fu, Tim M. Townes, Steven M. Rowe, David M. Bedwell, Jennifer Guimbellot, Rui Zhao

A major unmet need in the cystic fibrosis (CF) therapeutic landscape is the lack of effective treatments for nonsense CFTR mutations, which affect approximately 10% of CF patients. Correction of nonsense CFTR mutations via genomic editing represents a promising therapeutic approach. In this study, we tested whether prime editing, a novel CRISPR-based genomic editing method, can be a potential therapeutic modality to correct nonsense CFTR mutations. We generated iPSCs from a CF patient homozygous for the CFTR W1282X mutation. We demonstrated that prime editing corrected one mutant allele in iPSCs, which effectively restored CFTR function in iPSC-derived airway epithelial cells and organoids. We further demonstrated that prime editing may directly repair mutations in iPSC-derived airway epithelial cells when the prime editing machinery is efficiently delivered by helper-dependent adenovirus (HDAd). Together, our data demonstrated that prime editing may potentially be applied to correct CFTR mutations such as W1282X.
☐ ☆ ✇ International Wound Journal

Comparative study on gene expression in psoriatic lesions versus chronic wound healing processes

Por: Zhang Qiong · Fu Dongxue · Zhang Qing · Ren Yukun · An Yuepeng — Noviembre 28th 2023 at 04:50

Abstract

Psoriasis and chronic ulcers not only significantly impair quality of life but also pose a challenge in dermatological treatment. This study aimed to identify new therapeutic targets and biomarkers for psoriasis and chronic ulcers by comparing their gene expression profiles. The gene expression profiles of psoriatic, wound and chronic ulcer patients, as well as healthy controls, were determined via RNA extraction and next-generation sequencing of biopsies. In order to identify biomarkers, functional enrichment, differential expression analysis and machine learning algorithms were implemented. It is worth mentioning that the genes IL17A, TNF, KRT16, MMP9, and CD44 exhibited substantial correlations with the pathogenesis of the conditions being studied. As evidenced by their AUC-ROC values approaching 0.90, machine learning models accurately identified these biomarkers. The differential gene expression was consequently validated via qRT-PCR, which highlighted the increased expression of matrix remodelling enzymes and inflammatory cytokines. Additionally, genes essential for maintaining epidermis integrity and facilitating wound healing exhibited downregulation. These insights into the molecular mechanisms of psoriasis and chronic ulcers pave the way for the development of targeted therapies, offering hope for improved treatment strategies.

☐ ☆ ✇ International Wound Journal

Human umbilical cord mesenchymal stem cell‐derived exosomes combined with gelatin methacryloyl hydrogel to promote fractional laser injury wound healing

Por: Xinling Zhang · Pengbing Ding · Yujie Chen · Zhiyu Lin · Xun Zhao · Hongbin Xie — Noviembre 27th 2023 at 21:38

Abstract

To investigate whether human umbilical cord mesenchymal stem cell-derived exosomes combined with gelatin methacryloyl (GelMA) hydrogel are beneficial in promoting healing of laser-injured skin wounds in mice. Supernatants of cultured human umbilical cord mesenchymal stem cells (HUC-MSCs) were collected to obtain human umbilical cord MSC-derived exosomes (HUC-MSCs-Exos), which were combined with GelMA hydrogel complex to treat a mouse fractional laser injury model. The study was divided into PBS group, EX (HUC-MSCs-Exos) group, GEL (GelMA hydrogel) group and EX+GEL (HUC-MSCs-Exos combined with GelMA hydrogel) group. The healing of laser-injured skin in each group was observed by gross view and dermatoscopy, and changes in skin structure, angiogenesis and proliferation-related indexes were observed during the healing process of laser-injured skin in each group. The results of the animal experiments showed that the EX and GEL groups alone and the EL+EX group exhibited less inflammatory response compared to the PBS group. The EX and GEL groups showed marked tissue proliferation and favourable angiogenesis, which promoted the wound healing well. The GEL+EX group had the most significant promotion of wound healing compared to the PBS group. qPCR results showed that the expression levels of proliferation-related factors, including KI67 and VEGF and angiogenesis-related factor CD31, were significantly higher in the GEL+EX group than in the other groups, with a time-dependent effect. The combination of HUC-MSCs-Exos and GelMA hydrogel is beneficial in reducing the early inflammatory response of laser-injured skin in mice and promoting its proliferation and angiogenesis, which in turn promotes wound healing.

☐ ☆ ✇ PLOS ONE Medicine&Health

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis

Por: Yulian Wang · Weidong Yang · Lulu Liu · Lihong Liu · Jiepeng Chen · Lili Duan · Yuyuan Li · Shuzhuang Li — Noviembre 27th 2023 at 15:00

by Yulian Wang, Weidong Yang, Lulu Liu, Lihong Liu, Jiepeng Chen, Lili Duan, Yuyuan Li, Shuzhuang Li

Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.
☐ ☆ ✇ PLOS ONE Medicine&Health

Efficacy of mesenchymal stromal cells in the treatment of unexplained recurrent spontaneous abortion in mice: An analytical and systematic review of meta-analyses

Por: Xiaoxuan Zhao · Yijie Hu · Wenjun Xiao · Yiming Ma · Dan Shen · Yuepeng Jiang · Yi Shen · Suxia Wang · Jing Ma — Noviembre 27th 2023 at 15:00

by Xiaoxuan Zhao, Yijie Hu, Wenjun Xiao, Yiming Ma, Dan Shen, Yuepeng Jiang, Yi Shen, Suxia Wang, Jing Ma

Objectives

Unexplained recurrent spontaneous abortion (URSA) remains an intractable reproductive dilemma due to the lack of understanding of the pathogenesis. This study aimed to evaluate the preclinical evidence for the mesenchymal stromal cell (MSC) treatment for URSA.

Methods

A meticulous literature search was independently performed by two authors across the Cochrane Library, EMBASE, and PubMed databases from inception to April 9, 2023. Each study incorporated was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool. The amalgamated standardized mean difference (SMD) accompanied by 95% confidence interval (CI) were deduced through a fixed-effects or random-effects model analysis.

Results

A total of ten studies incorporating 140 mice were subjected to data analysis. The MSC treatment yielded a significant reduction in the abortion rate within the URSA model (OR = 0.23, 95%CI [0.17, 0.3], PP = 0.01), IL10 (SMD 1.60, 95% CI [0.58, 2.61], P = 0.002), IFN-γ (SMD -1.66, 95%CI [-2.79, -0.52], P = 0.004), and TNF-α (SMD -1.98, 95% CI [-2.93, -1.04], PPP>0.05).

Conclusions

The findings underscore the considerable potential of MSCs in URSA therapy. Nonetheless, the demand for enhanced transparency in research design and direct comparisons between various MSC sources and administration routes in URSA is paramount to engendering robust evidence that could pave the way for successful clinical translation.

☐ ☆ ✇ Journal of Clinical Nursing

Best evidence summary for prevention and management of enteral feeding intolerance in critically ill patients

Por: Fang Peng · Huaqin Wang · Jianzhi Li · Mengqi Ma · Xuemeng Jiang · Han Run · Qingting Li · Juanjuan Leng · Luwei Xiao · Li Tang — Noviembre 23rd 2023 at 08:23

Abstract

Aim

To evaluate and summarize the evidence for prevention and management of enteral feeding intolerance in critically ill patients and provide reference for clinical practice.

Design

This study was an evidence summary followed by the evidence summary reporting standard of Fudan University Center for Evidence-based Nursing.

Methods

Current literatures were systematically searched for the best evidence for prevention and management of enteral feeding intolerance in critically ill patients. Literature types included clinical guidelines, best practice information sheets, expert consensuses, systematic reviews, evidence summaries and cohort studies.

Data Sources

UpToDate, BMJ Best Practice, Joanna Briggs Institute, Guidelines International Network, National Institute for Health and Care Excellence, Registered Nurses Association of Ontario, Scottish Intercollegiate Guidelines Network, the Cochrane Library, Embase, PubMed, Sinomed, Web of Science, Yi Maitong Guidelines Network, DynaMed, MEDLINE, CNKI, WanFang database, Chinese Medical Journal Full-text Database, European Society for Clinical Nutrition and Metabolism website, the American Society for Parenteral and Enteral Nutrition website were searched from January 2012 to April 2023.

Results

We finally identified 18 articles that had high-quality results. We summarized the 24 pieces of best evidence from these articles, covering five aspects: screening and assessment of the risk of enteral nutritional tolerance; formulation of enteral nutrition preparations; enteral nutritional feeding implementation; feeding intolerance symptom prevention and management; and multidisciplinary management. Of these pieces of evidence, 19 were ‘strong’ and 5 were ‘weak’, 7 pieces of evidence were recommended in level one and 4 pieces of evidence were recommended in level two.

Conclusion

The following 24 pieces of evidence for prevention and management of enteral feeding intolerance in critically ill patients were finally recommended. However, as these evidences came from different countries, relevant factors such as the clinical environment should be evaluated before application. Future studies should focus on more specific symptoms of feeding intolerance and more targeted prevention design applications.

Implications for the profession and patient care

The clinical medical staffs are recommended to take evidence-based recommendations for the implementation of standardized enteral nutrition to improve patient outcomes and decrease gastrointestinal intolerance in critically ill patients.

Impact

The management of enteral nutrition feeding intolerance has always been a challenge and difficulty in critically ill patients. This study summarizes 24 pieces of the best evidence for prevention and management of enteral nutrition feeding intolerance in critically ill patients. Following and implementing these 24 pieces of evidence is beneficial to the prevention and management of feeding intolerance in clinical practice. The 24 pieces of evidence include five aspects, including screening and assessment of the risk of enteral nutritional tolerance, formulation of enteral nutrition preparations, enteral nutritional feeding implementation, feeding intolerance symptom prevention and management and multidisciplinary management. These five aspects constitute a good implementation process. Screening and assessment of enteral nutritional tolerance throughout intervention are important guarantees for developing a feasible nutrition program in critically ill patients. This study will be benefit to global medical workers in the nutritional management of critically ill patients.

Reporting Method

This evidence summary followed the evidence summary reporting specifications of Fudan University Center for Evidence-based Nursing, which were based on the methodological process for the summary of the evidence produced by the Joanna Briggs Institute (JBI). The reporting specifications include problem establishment, literature retrieval, literature screening, literature evaluation, the summary and grading of evidence and the formation of practical suggestions. This study was based on the evidence summary reporting specifications of the Fudan University Center for the Evidence-based Nursing, the register name is ‘Best evidence summary for prevention and management of enteral feeding intolerance in critically ill patients’, the registration number is ‘ES20231823’.

☐ ☆ ✇ PLOS ONE Medicine&Health

Heavy-tailed distributions of confirmed COVID-19 cases and deaths in spatiotemporal space

Por: Peng Liu · Yanyan Zheng — Noviembre 21st 2023 at 15:00

by Peng Liu, Yanyan Zheng

This paper conducts a systematic statistical analysis of the characteristics of the geographical empirical distributions for the numbers of both cumulative and daily confirmed COVID-19 cases and deaths at county, city, and state levels over a time span from January 2020 to June 2022. The mathematical heavy-tailed distributions can be used for fitting the empirical distributions observed in different temporal stages and geographical scales. The estimations of the shape parameter of the tail distributions using the Generalized Pareto Distribution also support the observations of the heavy-tailed distributions. According to the characteristics of the heavy-tailed distributions, the evolution course of the geographical empirical distributions can be divided into three distinct phases, namely the power-law phase, the lognormal phase I, and the lognormal phase II. These three phases could serve as an indicator of the severity degree of the COVID-19 pandemic within an area. The empirical results suggest important intrinsic dynamics of a human infectious virus spread in the human interconnected physical complex network. The findings extend previous empirical studies and could provide more strict constraints for current mathematical and physical modeling studies, such as the SIR model and its variants based on the theory of complex networks.
☐ ☆ ✇ International Wound Journal

Machine learning and single‐cell transcriptome profiling reveal regulation of fibroblast activation through THBS2/TGFβ1/P‐Smad2/3 signalling pathway in hypertrophic scar

Por: Binyu Song · Yuhan Zhu · Ying Zhao · Kai Wang · Yixuan Peng · Lin Chen · Zhou Yu · Baoqiang Song — Noviembre 21st 2023 at 08:23

Abstract

Hypertrophic scar (HS) is a chronic inflammatory skin disorder characterized by excessive deposition of extracellular matrix, and the mechanisms underlying their formation remain poorly understood. We analysed scRNA-seq data from samples of normal skin and HS. Using the hdWGCNA method, key gene modules of fibroblasts in HS were identified. Non-negative matrix factorization was employed to perform subtype analysis of HS patients using these gene modules. Multiple machine learning algorithms were applied to screen and validate accurate gene signatures for identifying and predicting HS, and a convolutional neural network (CNN) based on deep learning was established and validated. Quantitative reverse transcription-polymerase chain reaction and western blotting were performed to measure mRNA and protein expression. Immunofluorescence was used for gene localization analysis, and biological features were assessed through CCK8 and wound healing assay. Single-cell sequencing revealed distinct subpopulations of fibroblasts in HS. HdWGCNA identified key gene characteristics of this population, and pseudotime analysis was conducted to investigate gene variation during fibroblast differentiation. By employing various machine learning algorithms, the gene range was narrowed down to three key genes. A CNN was trained using the expression of these key genes and immune cell infiltration, enabling diagnosis and prediction of HS. Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFβ1/P-Smad2/3 pathway. Our study identifies unique fibroblast subpopulations closely associated with HS and provides biomarkers for the diagnosis and treatment of HS.

☐ ☆ ✇ PLOS ONE Medicine&Health

Data glove-based gesture recognition using CNN-BiLSTM model with attention mechanism

Por: Jiawei Wu · Peng Ren · Boming Song · Ran Zhang · Chen Zhao · Xiao Zhang — Noviembre 17th 2023 at 15:00

by Jiawei Wu, Peng Ren, Boming Song, Ran Zhang, Chen Zhao, Xiao Zhang

As a novel form of human machine interaction (HMI), hand gesture recognition (HGR) has garnered extensive attention and research. The majority of HGR studies are based on visual systems, inevitably encountering challenges such as depth and occlusion. On the contrary, data gloves can facilitate data collection with minimal interference in complex environments, thus becoming a research focus in fields such as medical simulation and virtual reality. To explore the application of data gloves in dynamic gesture recognition, this paper proposes a data glove-based dynamic gesture recognition model called the Attention-based CNN-BiLSTM Network (A-CBLN). In A-CBLN, the convolutional neural network (CNN) is employed to capture local features, while the bidirectional long short-term memory (BiLSTM) is used to extract contextual temporal features of gesture data. By utilizing attention mechanisms to allocate weights to gesture features, the model enhances its understanding of different gesture meanings, thereby improving recognition accuracy. We selected seven dynamic gestures as research targets and recruited 32 subjects for participation. Experimental results demonstrate that A-CBLN effectively addresses the challenge of dynamic gesture recognition, outperforming existing models and achieving optimal gesture recognition performance, with the accuracy of 95.05% and precision of 95.43% on the test dataset.
☐ ☆ ✇ PLOS ONE Medicine&Health

Emissions reduction strategy in a three-stage agrifood value chain: A dynamic differential game approach

Por: Huanhuan Wang · Xiaoli Fan · Qilan Zhao · Pengfei Cui — Noviembre 17th 2023 at 15:00

by Huanhuan Wang, Xiaoli Fan, Qilan Zhao, Pengfei Cui

Agrifood systems account for 31% of global greenhouse gas emissions. Substantial emissions reduction in agrifood systems is critical to achieving the temperature goal set by the Paris Agreement. A key challenge in reducing GHG emissions in the agrifood value chain is the imbalanced allocation of benefits and costs associated with emissions reduction among agrifood value chain participants. However, only a few studies have examined agrifood emissions reduction from a value chain perspective, especially using dynamic methods to investigate participants’ long-term emissions reduction strategies. This paper helps fill this gap in the existing literature by examining the impact of collaborations among agrifood value chain participants on correcting those misallocations and reducing emissions in agrifood systems. We develop a dynamic differential game model to examine participants’ long-term emissions reduction strategies in a three-stage agrifood value chain. We use the Hamilton-Jacobi-Bellman equation to derive the Nash equilibrium emissions reduction strategies under non-cooperative, cost-sharing, and cooperative mechanisms. We then conduct numerical analysis and sensitivity analysis to validate our model. Our results show that collaboration among value chain participants leads to higher emissions reduction efforts and profits for the entire value chain. Specifically, based on our numerical results, the cooperative mechanism results in the greatest emissions reduction effort by the three participants, which leads to a total that is nearly three times higher than that of the non-cooperative mechanism and close to two times higher than the cost-sharing mechanism. The cooperative mechanism also recorded the highest profits for the entire value chain, surpassing the non-cooperative and cost-sharing mechanisms by around 37% and 16%, respectively. Our results provide valuable insights for policymakers and agrifood industry stakeholders to develop strategies and policies encouraging emissions reduction collaborations in the agrifood value chain and reduce emissions in the agrifood systems.
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