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Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.
Diabetic foot ulcers are the prevalent complication of diabetes mellitus, frequently culminating in arteriosclerosis of the lower extremities and consequent development of chronic wounds. The effectiveness of electroacupuncture (EA) as therapeutic intervention for promoting wound healing in this particular group of patients has been comprehensively assessed in this study. A randomized controlled trial involving 380 early diabetic patients with arteriosclerotic lesions of the lower limbs was conducted. Standard wound care plus EA was administered to the treatment group, while standard wound care alone was administered to the control group. The principal outcome assessed was the reduction in lesion size following the 8-week treatment period. Pain scores, recuperation time, and quality of life (QoL) evaluations constituted secondary outcomes. In comparison to the control group, the treatment group exhibited a significantly greater reduction in wound size (p < 0.05). The treatment group exhibited significantly reduced pain scores and significantly higher QoL scores (p < 0.05). The duration of recovery did not vary substantially among the groups (p > 0.05). Electroacupuncture thus appeared to be an effective adjunctive treatment for early diabetic patients with lower limb arteriosclerotic lesions, promoting pain relief and quality of life. Additional investigation is necessary to validate these results and delve into the underlying mechanisms of action.
by Wenbo An, Xuechun Hu, He Chen, Qiqi Wang, Yonglin Zheng, Jiahui Wang, Junzhen Di
The inhibition and toxicity of high acidity and heavy metals on sulfate-reducing bacteria in acid mine drainage (AMD) were targeted. Highly active SRB immobilized particles were prepared using SRB, warm sticker wastes (iron powders), corncobs, and Maifan stones as the main matrix materials, employing microbial immobilization technology. The repair ability and reusability of highly active immobilized particles for AMD were explored. The results indicate that the adaptability of immobilized particles to AMD varied under different initial conditions, such as pH, Mn2+, and SO42-. The adsorption process of immobilized particles on Mn2+ follows the quasi-second-order kinetic model, suggesting that it involves both physical and chemical adsorption. The maximum adsorption capacity of immobilized particles for Mn2+ is 3.878 mg/g at a concentration of 2.0 mg/L and pH 6. On the other hand, the reduction process of immobilized particles on SO42- adheres to the first-order reaction kinetics, indicating that the reduction of SO42- is primarily driven by the dissimilation reduction of SRB. The maximum reduction rate of SO42- by immobilized particles is 94.23% at a concentration of 800 mg/L and pH 6. A layered structure with a flocculent appearance formed on the surface of the immobilized particles. The structure’s characteristics were found to be consistent with sulfate green rust (FeII4FeIII2(OH)12SO4·8H2O). The chemisorption, ion exchange, dissimilation reduction, and surface complexation occurring between the matrices in the immobilized particles can enhance the alkalinity of AMD and decrease the concentration of heavy metals and sulfates. These results are expected to offer novel insights and materials for the treatment of AMD using biological immobilization technology, as well as improve our understanding of the mechanisms behind biological and abiotic enhanced synergistic decontamination.by Junyu Zhang, Zhixi Hu, Yuquan Tan, Jiahao Ye
BackgroundHeart Failure (HF) is a widespread condition that affects millions of people, and it is caused by issues with the heart and blood vessels. Even though we know hypertension, coronary artery disease, obesity, diabetes, and genetics can increase the risk of HF and Chronic Kidney Disease (CKD), the exact cause of these conditions remains a mystery. To bridge this gap, we adopted Mendelian Randomization (MR), which relies on genetic variants as proxies.
MethodsWe used data from European populations for our Bidirectional Two-Sample MR Study, which included 930,014 controls and 47,309 cases of HF from the HERMES consortium, as well as 736,396 controls and 51,256 cases of CKD. We also employed several MR variations, including MR-Egger, Inverse Variance Weighted (IVW), and Weighted Median Estimator (WME), to guarantee the results were accurate and comprehensive.).
ResultsIn this study, the MR analysis found that individuals with a genetic predisposition for HF have an elevated risk of CKD. Our study revealed a significant association between the genetic prediction of HF and the risk of CKD, as evidenced by the IVW method [with an odds ratio (OR) of 1.12 (95% CI, 1.03–1.21), p = 0.009] and the WME [with an OR of 1.14 (95% CI, 1.03–1.26), p = 0.008]. This causal relationship remained robust even after conducting MR analysis while adjusting for the effects of diabetes and hypertension, yielding ORs of 1.13 (IVW:95% CI, 1.03–1.23), 1.12 (MR-Egger: 95% CI, 0.85–1.48), and 1.15 (WME:95% CI, 1.04–1.27) (p = 0.008). However, in the reverse analysis aiming to explore CKD and renal function as exposures and HF as the outcome, we did not observe a statistically significant causal link between CKD and HF.
ConclusionOur study demonstrates the significance of HF in CKD progression, thus having meaningful implications for treatment and the potential for discovering new therapies. To better understand the relationship between HF and CKD, we need to conduct research in a variety of populations.
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.
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 mm2
The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD.
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.
Advancements in 3D bioprinting, particularly the use of gelatin methacrylate (GelMA) hydrogels, are ushering in a transformative era in regenerative medicine and tissue engineering. This review highlights the pivotal role of GelMA hydrogels in wound healing and skin regeneration. Its biocompatibility, tunable mechanical properties and support for cellular proliferation make it a promising candidate for bioactive dressings and scaffolds. Challenges remain in optimizing GelMA hydrogels for clinical use, including scalability of 3D bioprinting techniques, durability under physiological conditions and the development of advanced bioinks. The review covers GelMA's applications from enhancing wound dressings, promoting angiogenesis and facilitating tissue regeneration to addressing microbial infections and diabetic wound healing. Preclinical studies underscore GelMA's potential in tissue healing and the need for further research for real-world applications. The future of GelMA hydrogels lies in overcoming these challenges through multidisciplinary collaboration, advancing manufacturing techniques and embracing personalized medicine paradigms.
On 20 July 2021, after the outbreak of COVID-19 at Nanjing Lukou International Airport, several universities started closed management and online teaching. This had a large impact on students’ daily life and study, which may lead to mental health problems. The purpose of this study is to study the effect of screen time on mental health status of university students and the possible mediating effect of sleep status.
This was a cross-sectional study. A web-based questionnaire survey was employed that included demographic characteristics, sleep status and mental health status (depression, anxiety and loneliness). The Pittsburgh Sleep Quality Index scale was used to assess sleep status, while the Centre for Epidemiologic Studies Depression (CES-D) scale, Generalised Anxiety Disorder-7 (GAD-7) scale and Emotional versus Social Loneliness Scale (ESLS) were used to assess depression, anxiety and loneliness, respectively. Linear and logistic regression models were developed and adjusted for confounding factors, and finally the mediating effects were tested using the Karlson-Holm-Breen method.
Finally, 1070 valid questionnaires were included. Among these, 604 (56.45%) indicated depressive symptoms (CES-D score ≥16) and 902 (84.30%) indicated anxiety symptoms (GAD-7 score ≥10). The mean ESLS score (for loneliness) was 26.51±6.64. The relationship between screen time and depressive symptoms (OR 1.118, 95% CI 1.072 to 1.166) and anxiety symptoms (OR 1.079, 95% CI 1.023 to 1.138) remained significant after adjusting for confounding factors. Meanwhile, sleep status plays an intermediary role in screen time and mental health status (depression and anxiety) and accounts for 13.73% and 19.68% of the total effects, respectively. We did not find a significant association between screen time and loneliness.
During the outbreak of COVID-19, screen time is inevitably prolonged among university students. There is a relationship between mental health and screen time, and sleep status plays a mediating role.
Chronic obstructive pulmonary disease (COPD) is a prevalent chronic lung disease characterised by persistent and progressive airflow obstruction resulting from tracheal and/or alveolar lesions. Patients afflicted with COPD endure a poor quality of life primarily due to the symptoms of the disease. Pulmonary rehabilitation (PR) constitutes a core component of the comprehensive management of individuals dealing with COPD. Nevertheless, suboptimal adherence and completion rates are the chief impediments associated with PR. Virtual reality (VR) is emerging as a promising approach to support patients with COPD in their PR journey. Currently, no comprehensive systematic review has evaluated the impact of VR as a PR adjunct in patients with COPD. We aimed to investigate and summarise the evidence from recent studies related to the effect of VR as an adjunct to PR in COPD cases.
We will conduct a comprehensive search of databases, including Web of Science, CINAHL, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, from their inception up to May 2023 to identify randomised controlled trials examining VR as an adjunct to PR in patients with COPD, with no restrictions on publication status or language. Our primary outcome measure will be the 6-min walk test. Two independent researchers will screen the literature for suitable articles for inclusion in this meta-analysis. Data collection and assessment of bias risk will be performed. This meta-analysis is intended to furnish data on each outcome as sufficient data become available. Heterogeneity will be assessed using the 2 test and I2 statistics. The current review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Ethical approval is waived due to the retrospective nature of this study. Furthermore, the findings will be disseminated through peer-reviewed journals.
CRD42022374736.
Postoperative delirium is a prominent and clinically important complication in older adults after coronary artery bypass grafting (CABG) surgery, resulting in prolonged hospital stay, long-term cognitive impairment and increased morbidity and mortality. Many studies have shown that cerebral desaturation is associated with increased risk of postoperative delirium during on-pump cardiac surgery. However, few studies have focused on the effect of optimising regional cerebral oxygen saturation (rSO2) on postoperative delirium during off-pump CABG. The purpose of this study is to investigate whether intraoperative anaesthetic management based on percutaneous cerebral oximetry monitoring decreases the incidence of postoperative delirium in older adults undergoing off-pump CABG.
This single-centre randomised controlled trial will randomly assign 200 patients to the intervention group or the control group at a ratio of 1:1. The patients in the intervention group will be observed by percutaneous cerebral oximetry monitoring that the desaturation (a drop of more than 20% from baseline value or rSO2 less than 55% for >60 consecutive seconds at either probe) during the procedure triggered the intervention strategies, while the cerebral oximetry data of the control group will be hidden from the clinical team and patients will be anaesthetised by the usual anaesthetic management. The primary outcome will be the incidence of postoperative delirium during the first 7 days after off-pump CABG. Delirium will be comprehensively evaluated by the combination of the Richmond Agitation Sedation Scale and the Confusion Assessment Method for the intensive care unit. The secondary outcomes will include the incidence of postoperative acute kidney injury and myocardial infarction during the hospital stay, as well as the intensive care unit and hospital length of stay.
This study was approved by the Ethics Committee of the Chinese Academy of Medical Sciences, Fuwai Hospital (No 2022–1824). Written informed consent will be obtained from each patient or their legal representatives before enrolment. The results of this trial will be published in an international peer-reviewed scientific journal.
ChiCTR2300068537.
Individuals with Parkinson’s disease (PD) often experience initial hesitation, slowness of movements, decreased balance and impaired standing ability, which can significantly impact their independence. Transcranial magnetic stimulation and transcranial direct current stimulation are two widely used and promising non-invasive brain stimulation (NIBS) modalities for treating PD. The supplementary motor area (SMA), associated with motor behaviour and processing, has received increasing attention as a potential stimulation target to alleviate PD-related symptoms. However, the data on NIBS over SMA in PD individuals are inconsistent and has not been synthesised. In this article, we will review the evidence for NIBS over SMA in PD individuals and evaluate its efficacy in improving PD function.
Randomised controlled clinical trials comparing the effects of NIBS and sham stimulation on motor function, activities of daily living and participation for people with PD will be included. A detailed computer-aided search of the literature will be performed from inception to February 2023 in the following databases: PubMed, EMBASE, Physiotherapy Evidence Database (PEDro), Web of Science (WOS) and The Chinese National Knowledge Infrastructure (CNKI). Two independent reviewers will screen articles for relevance and methodological validity. The PEDro scale will be used to evaluate the risk of bias of selected studies. Data from included studies will be extracted by two independent reviewers through a customised, preset data extraction sheet.
Ethical approval is not required for this systematic review. The study’s findings will be presented at scientific meetings and published in peer-reviewed journals.
CRD42023399945.
Craniotomies are intricate neurosurgical procedures susceptible to post-operative complications, among which surgical site infections (SSIs) are particularly concerning. This study sought to elucidate the potential risk factors and pathogenetic characteristics associated with SSIs following craniotomy procedures in a clinical setting. A retrospective study was conducted from May 2020 to May 2023, examining patients subjected to elective or emergency craniotomies. The cohort underwent post-operative surveillance for SSIs, facilitating patient classification into SSI and Non-SSI groups based on infection occurrence. Data collection encapsulated demographic and clinical parameters, including American Society of Anesthesiologists (ASA) classifications, and operative factors. SSIs were diagnosed via an integrated approach combining clinical symptoms, microbiological culture findings and pertinent laboratory tests. A rigorous statistical methodology employing IBM's SPSS version 27.0 was utilised for data analysis. In a univariate analysis, significant risk factors for post-craniotomy SSIs were identified, with patients aged over 60 displaying a pronounced susceptibility. Moreover, surgeries exceeding a duration of 4 h heightened infection risks. Elevated ASA grades denoted an increased prevalence of SSIs, as did emergency procedures and higher National Nosocomial Infections Surveillance scores. Multivariate analysis pinpointed epidural/subdural drainage as a protective measure against SSIs, whereas emergency surgeries, operative times beyond 4 h and subsequent surgeries within the hospital stay amplified infection risks. Notably, coagulase-negative Staphylococcus dominated the identified pathogens at 28.09%, followed by Escherichia coli (17.98%), Klebsiella pneumoniae (10.11%) and Staphylococcus aureus (11.24%), underscoring the need for diverse prophylactic measures. SSIs following craniotomies present a multifaceted challenge influenced by a confluence of patient-related, operative and post-operative determinants. Understanding these risk factors is paramount in refining surgical protocols and post-operative care strategies to mitigate SSI incidence.
The goal of this overview of systematic reviews (SRs) and meta-analyses (MAs) was to methodically gather, evaluate and summarize the data supporting the use of hyperbaric oxygen therapy (HBOT) to treat diabetic foot ulcers (DFUs). The Cochrane Library, Embase, PubMed, Web of Science and Embase were all searched thoroughly to identify SRs/MAs that qualified. AMSTAR-2 tool, PRISMA checklists and GRADE system were applied by two reviewers independently to assess the methodological quality, reporting and evidence quality of the included SRs/MAs, respectively. Eleven SRs/MAs were enrolled in this overview. According to AMSTAR-2, a very low methodological quality assessment was given to the included SRs/MAs due to the limitations of items 2, 4 and 7. For the PRISMA, the overall quality of reporting is not satisfactory due to missing reporting on protocol, search, as well as additional analysis. The majority of outcomes had low- to moderate-quality evidence, and no high-quality evidence was found to support the role of HBOT for DFUs, according to GRADE. To conclude, the potential of HBOT in treating DFUs is supported by evidence of low to moderate quality. More rigorously designed, high-level studies are needed in the future to determine the evidence for HBOT for DFU, including the timing, frequency and duration of HBOT interventions.
by Guanghao Xin, Jingyan Niu, Qinghua Tian, Yanchi Fu, Lixia Chen, Tingting Yi, Kuo Tian, Xuesong Sun, Na Wang, Jianjian Wang, Huixue Zhang, Lihua Wang
BackgroundParkinson’s disease is the second most common neurodegenerative disease in the world. However, current diagnostic methods are still limited, and available treatments can only mitigate the symptoms of the disease, not reverse it at the root. The immune function has been identified as playing a role in PD, but the exact mechanism is unknown. This study aimed to search for potential immune-related hub genes in Parkinson’s disease, find relevant immune infiltration patterns, and develop a categorical diagnostic model.
MethodsWe downloaded the GSE8397 dataset from the GEO database, which contains gene expression microarray data for 15 healthy human SN samples and 24 PD patient SN samples. Screening for PD-related DEGs using WGCNA and differential expression analysis. These PD-related DEGs were analyzed for GO and KEGG enrichment. Subsequently, hub genes (dld, dlk1, iars and ttd19) were screened by LASSO and mSVM-RFE machine learning algorithms. We used the ssGSEA algorithm to calculate and evaluate the differences in nigrostriatal immune cell types in the GSE8397 dataset. The association between dld, dlk1, iars and ttc19 and 28 immune cells was investigated. Using the GSEA and GSVA algorithms, we analyzed the biological functions associated with immune-related hub genes. Establishment of a ceRNA regulatory network for immune-related hub genes. Finally, a logistic regression model was used to develop a PD classification diagnostic model, and the accuracy of the model was verified in three independent data sets. The three independent datasets are GES49036 (containing 8 healthy human nigrostriatal tissue samples and 15 PD patient nigrostriatal tissue samples), GSE20292 (containing 18 healthy human nigrostriatal tissue samples and 11 PD patient nigrostriatal tissue samples) and GSE7621 (containing 9 healthy human nigrostriatal tissue samples and 16 PD patient nigrostriatal tissue samples).
ResultsUltimately, we screened for four immune-related Parkinson’s disease hub genes. Among them, the AUC values of dlk1, dld and ttc19 in GSE8397 and three other independent external datasets were all greater than 0.7, indicating that these three genes have a certain level of accuracy. The iars gene had an AUC value greater than 0.7 in GES8397 and one independent external data while the AUC values in the other two independent external data sets ranged between 0.5 and 0.7. These results suggest that iars also has some research value. We successfully constructed a categorical diagnostic model based on these four immune-related Parkinson’s disease hub genes, and the AUC values of the joint diagnostic model were greater than 0.9 in both GSE8397 and three independent external datasets. These results indicate that the categorical diagnostic model has a good ability to distinguish between healthy individuals and Parkinson’s disease patients. In addition, ceRNA networks reveal complex regulatory relationships based on immune-related hub genes.
ConclusionIn this study, four immune-related PD hub genes (dld, dlk1, iars and ttd19) were obtained. A reliable diagnostic model for PD classification was developed. This study provides algorithmic-level support to explore the immune-related mechanisms of PD and the prediction of immune-related drug targets.
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.
Surgical site infection (SSI) is one of the common postoperative complications after craniotomy for glioblastoma patients. Previous studies have investigated the risk factors for SSI in patients with glioblastoma. Whereas big differences in research results exist, and the correlation coefficients of different research results are quite different. A meta-analysis was conducted to examine the risk factors related to surgical site infection in patients with glioblastoma. We searched English databases to collect case–control studies or cohort studies published before 15 October 2023 including PubMed, Web of Science, Embase. The risk of bias of the included studies was assessed via Newcastle-Ottawa Scale. The analysis was performed using RevMan 5.4.1 tool. A total of 4 articles (n = 2222) were selected in this meta-analysis. The following risk factors were presented to be correlated with SSI in glioblastoma: irradiation (OR = 1.88, 95% CI [0.46, 7.60]), more than 3 surgeries (OR = 2.99, 95% CI [1.47, 6.08]). Occurrence of SSI is influenced by a variety of factors. Thus, we should pay close attention to high-risk subjects and take crucial targeted interventions to lower the SSI risk following craniotomy. Owing to the limited quality and quantity of the included studies, more rigorous studies with adequate sample sizes are needed to verify the conclusion.
by Shuang Xu, Qiongyu Zhang, Jiayan Zhou
The objective of this study was to investigate the direct effects of pain-induced depression and anxiety, as well as the mediating role of psychological resilience, on the psychological distress associated with rheumatoid arthritis. The method involved a sample of 196 patients with rheumatoid arthritis and applied the Hospital Anxiety and Depression Scale, Connor–Davidson Resilience Scale, and visual analog scale for pain. Bivariate and path analyses were performed, and a multiple mediational model was utilized. Results showed that all correlations among study variables were significant (pby 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.The high incidences of both the developmental delay among young children and the mental health problems of their caregivers are major threats to public health in low-income and middle-income countries. Parental training interventions during early childhood have been shown to benefit early development, yet evidence on strategies to promote caregiver mental health remains limited. In addition, evidence on the optimal design of scalable interventions that integrate early child development and maternal mental health components is scarce.
We design a single-blind, factorial, cluster-randomised controlled, superiority trial that will be delivered and supervised by local agents of the All China Women’s Federation (ACWF), the nationwide, government-sponsored social protection organisation that aims to safeguard the rights and interests of women and children. We randomise 125 villages in rural China into four arms: (1) a parenting stimulation arm; (2) a caregiver mental health arm; (3) a combined parenting stimulation and caregiver mental health arm and (4) a pure control arm. Caregivers and their children (aged 6–24 months at the time of baseline data collection) are selected and invited to participate in the 12-month-long study. The parenting stimulation intervention consists of weekly, one-on-one training sessions that follow a loose adaptation of the Reach Up and Learn curriculum. The caregiver mental health intervention is comprised of fortnightly group activities based on an adaptation of the Thinking Healthy curriculum from the WHO. Primary outcomes include measures of child development and caregiver mental health. Secondary outcomes include a comprehensive set of physical, psychological and behavioural outcomes. This protocol describes the design and evaluation plan for this programme.
This study received approval from the Institutional Review Board of Stanford University (IRB Protocol #63680) and the Institutional Review Board of the Southwestern University of Finance and Economics in Chengdu, Sichuan, China. Informed oral consent will be obtained from all caregivers for their own and their child’s participation in the study. The full protocol will be publicly available in an open-access format. The study findings will be published in economics, medical and public health journals, as well as Chinese or English policy briefs.
AEA RCT Registry (AEARCTR-0010078) and ISRCTN registry (ISRCTN84864201).
Stroke remains the second leading cause of death worldwide, a common cause of which is intracranial atherosclerotic stenosis (ICAS). Medical treatment is recommended as first-line therapy for treating ICAS, but the recurrence rate remains high. Drug-coated balloon (DCB) angioplasty has been designed to lower the risk of recurrent stenosis, holding therapeutic promise in the treatment of ICAS. However, the benefits of DCB require further evaluation.
The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols was followed to develop this protocol. We will systematically search online databases including Cochrane Central Register of Controlled Trials, PubMed, Web of Science, EMBASE, China Biological Medicine Database, ClinicalTrials.gov and WHO ICTRP from 1 January 2011 to the date of search. This will be supplemented by a manual search of unpublished and ongoing trials to manually select articles for inclusion. Inclusion criteria are randomised or quasi-randomised clinical trials and observational studies that investigated DCB or medical treatment for patients with a symptomatic ICAS of 50%–99%. The primary outcome is short-term composite safety including death of any cause, or non-fatal stroke. Secondary outcomes include long-term death or stroke, restenosis, neurological rehabilitation, quality of life and other complications. The available data will be analysed using meta-analysis, if appropriate. The evaluation of heterogeneity and biases will be guided by the Cochrane Handbook for Systematic Reviews of Interventions.
This systematic review does not require ethical approval as all available data from eligible studies will be anonymous with no concerns regarding privacy. Our findings will be disseminated through international conferences and peer-reviewed publications. Additional data from the study are available on request to corresponding authors via email.
CRD42022341607.
by Junghyun Kim, Jenny Jiang, Sophie Shen, Soko Setoguchi
ObjectivesTo describe inpatient and outpatient cardiac rehabilitation (CR) utilization patterns over time and by subgroups among patients admitted for acute heart failure (AHF) in Japan.
BackgroundCardiac rehabilitation (CR) is a crucial secondary prevention strategy for patients with heart failure. While the number of older patients with AHF continues to rise, trends in inpatient and outpatient CR participation following AHF in Japan have not been described to date.
MethodsWe conducted a retrospective cohort study of adult patients hospitalized for AHF in Japan between April 2008 and December 2020. Using data from the Medical Data Vision database, we measured trends in inpatient and outpatient CR participation following AHF. Descriptive analyses and summary statistics for AHF patients by CR participation status were reported.
ResultsThe analytic cohort included 88,052 patients. Among these patients, 37,810 (42.9%) participated in inpatient and/or outpatient CR. Of those, 36,431 (96.4%) participated in inpatient CR only and 1,277 (3.4%) participated in both inpatient and outpatient CR. Rates of inpatient CR rose more than 6-fold over the study period, from 9% in 2009 to 55% in 2020, whereas rates of outpatient CR were consistently low.
ConclusionsThe rate of inpatient CR participation among AHF patients in Japan rose dramatically over a 12-year period, whereas outpatient CR following AHF was vastly underutilized. Further study is needed to assess the clinical effectiveness of inpatient CR and to create infrastructure and incentives to support and encourage outpatient CR.
FreshRSS 