Explore the vast range of titles available.

Background Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. Main body of the abstract We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn’s Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. Short conclusion MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs’ efficacy.

Wildfire damage is expected to increase under climate warming. Research now suggests that increased human exposure to wildfires will be driven primarily by population growth in areas with frequent wildfires, rather than by a general increase in fire area. Wildfires are an important component of terrestrial ecosystem ecology but also a major natural hazard to societies, and their frequency and spatial distribution must be better understood 1 . At a given location, risk from wildfire is associated with the annual fraction of burned area, which is expected to increase in response to climate warming 1 , 2 , 3 . Until recently, however, only a few global studies of future fire have considered the effects of other important global environmental change factors such as atmospheric CO 2 levels and human activities, and how these influence fires in different regions 4 , 5 . Here, we contrast the impact of climate change and increasing atmospheric CO 2 content on burned area with that of demographic dynamics, using ensembles of climate simulations combined with historical and projected population changes under different socio-economic development pathways for 1901–2100. Historically, humans notably suppressed wildfires. For future scenarios, global burned area will continue to decline under a moderate emissions scenario, except for low population growth and fast urbanization, but start to increase again from around mid-century under high greenhouse gas emissions. Contrary to common perception, we find that human exposure to wildfires increases in the future mainly owing to projected population growth in areas with frequent wildfires, rather than by a general increase in burned area.

Wildfires are by far the largest contributor to global biomass burning and constitute a large global source of atmospheric traces gases and aerosols. Such emissions have a considerable impact on air quality and constitute a major health hazard. Biomass burning also influences the radiative balance of the atmosphere and is thus not only of societal, but also of significant scientific interest. There is a common perception that climate change will lead to an increase in emissions as hot and dry weather events that promote wildfire will become more common. However, even though a few studies have found that the inclusion of CO2 fertilisation of photosynthesis and changes in human population patterns will tend to somewhat lower predictions of future wildfire emissions, no such study has included full ensemble ranges of both climate predictions and population projections, including the effect of different degrees of urbanisation. Here, we present a series of 124 simulations with the LPJ-GUESS-SIMFIRE global dynamic vegetation-wildfire model, including a semi-empirical formulation for the prediction of burned area based on fire weather, fuel continuity and human population density. The simulations use Climate Model Intercomparison Project 5 (CMIP5) climate predictions from eight Earth system models. These were combined with two Representative Concentration Pathways (RCPs) and five scenarios of future human population density based on the series of Shared Socioeconomic Pathways (SSPs) to assess the sensitivity of emissions to the effect of climate, CO2 and humans. In addition, two alternative parameterisations of the semi-empirical burned-area model were applied. Contrary to previous work, we find no clear future trend of global wildfire emissions for the moderate emissions and climate change scenario based on the RCP 4.5. Only historical population change introduces a decline by around 15% since 1900. Future emissions could either increase for low population growth and fast urbanisation, or continue to decline for high population growth and slow urbanisation. Only for high future climate change (RCP8.5), wildfire emissions start to rise again after ca. 2020 but are unlikely to reach the levels of 1900 by the end of the 21st century. We find that climate warming will generally increase the risk of fire, but that this is only one of several equally important factors driving future levels of wildfire emissions, which include population change, CO2 fertilisation causing woody thickening, increased productivity and fuel load and faster litter turnover in a warmer climate.

Nucleic acid-based drugs offer a potentially effective tool for treatment of a variety of diseases, including cancer, cardiovascular diseases, neurological disorders and infectious diseases. However, clinical applications are hindered by instability of RNA molecules in the circulation and lack of efficient vectors that can deliver RNAs to target tissues and into diseased target cells. Synthetic polymer and lipids as well as virus-based vectors are among the most widely explored vehicles for RNA delivery, but clinical progress has been limited as a result of issues related to toxicity, immunogenicity and low efficiency. Most recently, the discovery that extracellular vesicles (EVs) are endogenous RNA carriers, which may display better biocompatibility and higher delivery efficiency as compared with the synthetic systems, has provided a ray of hope in coping with the delivery dilemma, and EV-based gene therapy has already sparked general interest both in academia and industry. In this review, the current knowledge on EV biology and their role in cell–cell communication will be summarized. Promises of EVs as drug carriers and recent technologies on tailoring EVs’ biological attributes will be included, and preclinical studies in which EVs have shown promise for therapeutic RNA delivery will be discussed.

Objective To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection. Methods The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated. Results The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group. Conclusion For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.

Summary An inverse relationship between osteoarthritis and osteoporosis has been debated over years. The microstructure of the femoral heads from postmenopausal osteoarthritic and osteoporotic women was evaluated with micro-CT. Significant differences were observed in microstructural parameters between them. Different microstructure might relate to the opposite bone defects in osteoarthritis and osteoporosis. Introduction This study was undertaken to verify the inverse relationship between osteoarthritis (OA) and osteoporosis (OP) by comparing the structural and mechanical indices. Methods Femoral head specimens were obtained from 17 postmenopausal women (OA, n = 8; OP, n = 9) during hip surgery. The microstructural parameters were measured with micro-CT. Mechanical test was performed after bone cube scanning. Results Significant difference in bone volume fraction (BV/TV) and trabecular thickness was noted between OA and OP groups. Structure model index decreased in OA, and increased in OP. The higher apparent density (AD) and lower material density (MD) were also shown in OA. Different from OP, positive correlation were noted between connectivity density and mechanical indices in OA. In OA group, BV/TV was associated with Young's modulus and AD, while trabecular number was the only parameter that correlated with MD. However, in OP group, only BV/TV correlated with yield strength, AD, and MD. Conclusions We observed the difference in microstructure between postmenopausal women with OA and OP, which might relate to the opposite bone defects in OA and OP. BV/TV might play an important role in mechanical properties of the subchondral bone in either OA or OP.

Molecular differences between individual cells can lead to dramatic differences in cell fate, such as death versus survival of cancer cells upon drug treatment. These originating differences remain largely hidden due to difficulties in determining precisely what variable molecular features lead to which cellular fates. Thus, we developed Rewind, a methodology that combines genetic barcoding with RNA fluorescence in situ hybridization to directly capture rare cells that give rise to cellular behaviors of interest. Applying Rewind to BRAF V600E melanoma, we trace drug-resistant cell fates back to single-cell gene expression differences in their drug-naive precursors (initial frequency of ~1:1,000–1:10,000 cells) and relative persistence of MAP kinase signaling soon after drug treatment. Within this rare subpopulation, we uncover a rich substructure in which molecular differences among several distinct subpopulations predict future differences in phenotypic behavior, such as proliferative capacity of distinct resistant clones after drug treatment. Our results reveal hidden, rare-cell variability that underlies a range of latent phenotypic outcomes upon drug exposure. A new methodology, Rewind, traces vemurafenib-resistant melanoma back to its initial cell state before drug treatment, creating, effectively, a cellular time machine.

Background The transitional period from hospital to home is vital for stroke patients, but it poses serious challenges. Good self-management ability can optimize disease outcomes. However, stroke patients in China have a low level of self-management ability during the transitional period, and a lack of effective support may be the reason. With the rapid development of technology, using wearable monitors to achieve real-time and individualized support may be the key to solving this problem. This study uses a randomized controlled trial design to assess the efficacy of using wearable technology to realize real-time and individualized self-management support in stroke patients’ self-management behavior during the transitional period following discharge from hospital. Methods This parallel-group randomized controlled trial will be conducted in two hospitals and patients’ homes. A total of 183 adult stroke patients will be enrolled in the study and randomly assigned to three groups in a 1:1:1 ratio. The smartwatch intervention group ( n  = 61) will receive Real-time and Individualized Self-management Support (RISS) program + routine care, the wristband group ( n  = 61) will wear a fitness tracker (self-monitoring) + routine care, and the control group ( n  = 61) will receive routine stroke care. The intervention will last for 6 months. The primary outcomes are neurological function status, self-management behavior, quality of life, biochemical indicators, recurrence rate, and unplanned readmission rate. Secondary outcomes are resilience, patient activation, psychological status, and caregiver assessments. The analysis is intention-to-treat. The intervention effect will be evaluated at baseline (T0), 2 months after discharge (T1), 3 months after discharge (T2), and 6 months after discharge (T3). Discussion The cloud platform designed in this study not only has the function of real-time recording but also can push timely solutions when patients have abnormal conditions, as well as early warnings or alarms. This study could also potentially help patients develop good self-management habits through resilience theory, wearable devices, and individualized problem–solution library of self-management which can lay the foundation for long-term maintenance and continuous improvement of good self-management behavior in the future. Trial registration The ethics approval has been granted by the Ethics Committee of West China Hospital, Sichuan University (2022–941). All patients will be informed of the study details and sign a written informed consent form before enrollment. The research results will be reported in conferences and peer-reviewed publications. The trial registration number is ChiCTR2300070384 . Registered on 11 April 2023.

Cardiac progenitor cells derived from adult heart have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are known to mediate cell–cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we investigated the cardiac progenitor cell (CPC)-derived exosomal miRNAs on protecting myocardium under oxidative stress. Sca1 + CPCs-derived exosomes were purified from conditional medium, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting using CD63, CD9 and Alix as markers. Exosomes production was measured by NTA, the result showed that oxidative stress-induced CPCs secrete more exosomes compared with normal condition. Although six apoptosis-related miRNAs could be detected in two different treatment-derived exosomes, only miR-21 was significantly upregulated in oxidative stress-induced exosomes compared with normal exosomes. The same oxidative stress could cause low miR-21 and high cleaved caspase-3 expression in H9C2 cardiac cells. But the cleaved caspase-3 was significantly decreased when miR-21 was overexpressed by transfecting miR-21 mimic. Furthermore, miR-21 mimic or inhibitor transfection and luciferase activity assay confirmed that programmed cell death 4 (PDCD4) was a target gene of miR-21, and miR-21/PDCD4 axis has an important role in anti-apoptotic effect of H9C2 cell. Western blotting and Annexin V/PI results demonstrated that exosomes pre-treated H9C2 exhibited increased miR-21 whereas decreased PDCD4, and had more resistant potential to the apoptosis induced by the oxidative stress, compared with non-treated cells. These findings revealed that CPC-derived exosomal miR-21 had an inhibiting role in the apoptosis pathway through downregulating PDCD4. Restored miR-21/PDCD4 pathway using CPC-derived exosomes could protect myocardial cells against oxidative stress-related apoptosis. Therefore, exosomes could be used as a new therapeutic vehicle for ischemic cardiac disease.