Serum Procalcitonin, Hematology Parameters, and Cell Morphology in Multiple Clinical Conditions and Sepsis.

BACKGROUND: The clinical value of procalcitonin (PCT) in infection diagnosis and antibiotic stewardship is still unclear. This study aimed to investigate the association between serum PCT and different clinical conditions as well as other infectious/inflammatory parameters in different septic patients in order to elucidate the value of PCT detection in infection management. METHODS: Chemiluminescence immunoassay was used for serum PCT analysis. Hematology analysis was used for complete blood cell count. Digital automated cell morphology analysis was used for blood cell morphology examination. Blood, urine, and stool cultures were performed according to routine clinical laboratory standard operating procedures. C-reactive protein (CRP) was analyzed by immunoturbidimetry. Erythrocyte sedimentation rate test was performed using natural sedimentation methods. RESULTS: Outpatients, ICU patients, and patients under 2 years of age with respiratory infections had higher serum PCT levels. Septic patients had the highest-serum PCT levels and other infection indexes. PCT levels in the blood, urine, and stool culture-positive patients were significantly higher than in culture-negative patients. The neutrophil granulation and reactive lymphocytes were observed together with the PCT-level increments in different septic patients, and these alterations were lessened after treatment. There was no significant change in monocyte morphology between pre- and posttreatment septic patients. CONCLUSIONS: Serum PCT is associated with neutrophil cytotoxicity and lymphocyte morphology changes in sepsis; thus, the combination of neutrophil and lymphocyte digital cell morphology evaluations with PCT detection may be a useful examination for guiding the clinical management of sepsis.

Ethical considerations in public engagement: developing tools for assessing the boundaries of research and involvement.

Public engagement with research (PEwR) has become increasingly integral to research practices. This paper explores the process and outcomes of a collaborative effort to address the ethical implications of PEwR activities and develop tools to navigate them within the context of a University Medical School. The activities this paper reflects on aimed to establish boundaries between research data collection and PEwR activities, support colleagues in identifying the ethical considerations relevant to their planned activities, and build confidence and capacity among staff to conduct PEwR projects. The development process involved the creation of a taxonomy outlining key terms used in PEwR work, a self-assessment tool to evaluate the need for formal ethical review, and a code of conduct for ethical PEwR. These tools were refined through iterative discussions and feedback from stakeholders, resulting in practical guidance for researchers navigating the ethical complexities of PEwR. Additionally, reflective prompts were developed to guide researchers in planning and conducting engagement activities, addressing a crucial aspect often overlooked in formal ethical review processes. The paper reflects on the broader regulatory landscape and the limitations of existing approval and governance processes, and prompts critical reflection on the compatibility of formal approval processes with the ethos of PEwR. Overall, the paper offers insights and practical guidance for researchers and institutions grappling with ethical considerations in PEwR, contributing to the ongoing conversation surrounding responsible research practices.

Genome sequencing of Elaeocarpus spp. stem blight pathogen Pseudocryphonectria elaeocarpicola reveals potential adaptations to colonize woody bark.

BACKGROUND: Elaeocarpus spp. stem blight, caused by Pseudocryphonectria elaeocarpicola, is a destructive disease, which will significantly reduce the productivity and longevity of Elaeocarpus spp. plants, especially in the Guangdong Province of China. However, few information is available for P. elaeocarpicola. To unravel the potential adaptation mechanism of stem adaptation, the whole genome of P. elaeocarpicola was sequenced by using the DNBSEQ and PacBio platforms. RESULTS: P. elaeocarpicola harbors 44.49 Mb genome with 10,894 predicted coding genes. Genome analysis revealed that the P. elaeocarpicola genome encodes a plethora of pathogenicity-related genes. Analysis of carbohydrate-active enzymes (CAZymes) revealed a rich variety of enzymes participated in plant cell wall degradation, which could effectively degrade cellulose, hemicellulose and xyloglucans in the plant cell wall and promote the invasion of the host plant. There are 213 CAZyme families found in P. elaeocarpicola, among which glycoside hydrolase (GH) family has the largest number, far exceeding other tested fungi by 53%. Besides, P. elaeocarpicola has twice as many genes encoding chitin and cellulose degradation as Cryphonectria parasitica, which belong to the same family. The predicted typical secreted proteins of P. elaeocarpicola are numerous and functional, including many known virulence effector factors, indicating that P. elaeocarpicola has great potential to secrete virulence effectors to promote pathogenicity on host plants. AntiSMASH revealed that the genome encoded 61 secondary metabolic gene clusters including 86 secondary metabolic core genes which was much higher than C. parasitica (49). Among them, two gene cluster of P. elaeocarpicola, cluster12 and cluster52 showed 100% similarity with the mycotoxins synthesis clusters from Aspergillus steynii and Alternaria alternata, respectively. In addition, we annotated cytochrome P450 related enzymes, transporters, and transcription factors in P. elaeocarpicola, which are important virulence determinants of pathogenic fungi. CONCLUSIONS: Taken together, our study represents the first genome assembly for P. elaeocarpicola and reveals the key virulence factors in the pathogenic process of P. elaeocarpicola, which will promote our understanding of its pathogenic mechanism. The acquired knowledge lays a foundation for further exploration of molecular interactions with the host and provide target for management strategies in future research.

3D nanofiber scaffolds from 2D electrospun membranes boost cell penetration and positive host response for regenerative medicine.

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 µm). It was found that scaffolds with a mesh size of 500 µm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.

Patients' experiences of GP consultations following the introduction of the new GP contract in Scotland: a cross-sectional survey.

BACKGROUND: The new Scottish GP contract commenced in April 2018 with a stated aim of mitigating health inequalities. AIM: To determine the health characteristics and experiences of patients consulting GPs in deprived urban (DU), affluent urban (AU), and remote and rural (RR) areas of Scotland. DESIGN AND SETTING: In 2022, a postal survey of a random sample of adult patients from 12 practices who had consulted a GP within the previous 30 days was undertaken. METHOD: Patient characteristics and consultation experiences in the three areas (DU, AU, RR) were evaluated using validated measures including the Consultation and Relational Empathy (CARE) Measure and Patient Enablement Instrument (PEI). RESULTS: In total, 1053 responses were received. In DU areas, multimorbidity was more common (78% versus 58% AU versus 68% RR, P<0.01), complex presentations (where the consultation addressed both psychosocial and physical problems) were more likely (16% versus 10% AU versus 11% RR, P<0.05), and more consultations were conducted by telephone (42% versus 31% AU versus 31% RR, P<0.01). Patients in DU areas reported lower satisfaction (82% DU completely, very, or fairly satisfied versus 90% AU versus 86% RR, P<0.01), lower perceived GP empathy (mean CARE score 38.9 versus 42.1 AU versus 40.1 RR, P<0.05), lower enablement (mean PEI score 2.6 versus 3.2 AU versus 2.8 RR, P<0.01), and less symptom improvement (P<0.01) than those in AU or RR areas. Face-to-face consultations were associated with significantly higher satisfaction, enablement, and perceived GP empathy than telephone consultations in RR areas (all P<0.05). CONCLUSION: Four years after the start of the new GP contract in Scotland, patients' experiences of GP consultations suggest that the inverse care law persists.

MicroRNA miR-181d-5p regulates the MAPK signaling pathway by targeting mitogen-activated protein kinase 8 (MAPK8) to improve lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a common immune disease. The microRNA (miR)-181d-5p is a potential target for treating kidney injury. However, the therapeutic role of miR-181d-5p in LN has not been investigated. This study aimed to investigate the role of miR-181d-5p in targeting mitogen-activated protein kinase 8 (MAPK8) and stimulating the MAPK signaling pathway in LN. METHODS: RT-qPCR was performed to identify the variations in miR-181d-5p expression in peripheral blood mononuclear cells (PBMCs) obtained from 42 LN patients, 30 healthy individuals, 6 MRL/lpr mice and 6 C57BL/6 mice. Western blot was used to detect the effect of miR-181d-5p on the MAPK signaling pathway in THP-1 cells and MRL/lpr mice. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the effect of miR-181d-5p on antinuclear antibodies and inflammatory factors. A dual-luciferase reporter assay was used to verify whether miR-181d-5p directly targets MAPK8. Flow cytometry was performed to evaluate apoptosis rates in transfected THP-1 cells. RESULTS: miR-181d-5p expression was downregulated in PBMCs of LN patients (P < 0.01) and MRL/lpr mice (P < 0.05). A dual luciferase reporter assay demonstrated that miR-181d-5p inhibits MAPK8 (P < 0.01). Overexpression of miR-181d-5p inhibited the phosphorylation of p38 (P < 0.001) and p44/42 (P < 0.01). Moreover, miR-181d-5p decreased the apoptosis rate of THP-1 cells (P < 0.001), and reduced the secretion of IL-6 (P < 0.01) and TNF-α (P < 0.01). Furthermore, overexpression of miR-181d-5p decreased anti-dsDNA antibody (P < 0.05), anti-Sm antibody (P < 0.01), and fibrosis levels in MRL/lpr mice. CONCLUSION: Upregulation of miR-181d-5p showed anti-inflammatory and anti-apoptotic effects on THP-1 cells in vitro and kidney injury in vivo. These effects were achieved by miR-181d-5p targeting MAPK8 to inhibit phosphorylation of p38 and p44/42. These results may offer new insights for improving therapeutic strategies against lupus nephritis.

Primary care transformation in Scotland: a qualitative study of GPs' and multidisciplinary team members' views.

BACKGROUND: The Scottish Government's vision to transform primary care includes expansion of the primary care multidisciplinary team (MDT), formalised in the new GP contract in April 2018. AIM: To explore practitioners' views on the expansion of MDT working in Scotland. DESIGN AND SETTING: Qualitative study with GPs and a range of MDT staff working in three different population settings in Scotland. METHOD: In-depth semi-structured interviews were carried out by telephone with 8 GPs and 19 MDT staff between May and June 2022. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was conducted to identify commonalities and divergences in the interviews. RESULTS: Internal challenges facing MDT staff included adapting to the fast pace of primary care, building new relationships, training and professional development needs, line management issues, and monitoring and evaluation of performance. External challenges included the ongoing effects of the COVID-19 pandemic, lack of time, difficulties with hybrid working, and low staff morale. Most GPs reported that expansion of their roles as expert medical specialists had not yet happened because their workload had not decreased (and in many cases had increased). In deprived areas, insufficient resources to deal with the high numbers of patients with complex multimorbidity remained a key issue. Interviewees in remote and rural settings felt the new contract did not take into account the unique challenges of providing primary care services in such areas, and recruitment and accommodation were cited as particular problems. CONCLUSION: Although there has been substantial expansion of the primary care MDT, which most GPs welcome, many challenges to effective implementation remain that must be addressed if transformation of primary care in Scotland is to become a reality.

Calcium sulfate-Cu2+ delivery system improves 3D-Printed calcium silicate artificial bone to repair large bone defects.

There are still limitations in artificial bone materials used in clinical practice, such as difficulty in repairing large bone defects, the mismatch between the degradation rate and tissue growth, difficulty in vascularization, an inability to address bone defects of various shapes, and risk of infection. To solve these problems, our group designed stereolithography (SLA) 3D-printed calcium silicate artificial bone improved by a calcium sulfate-Cu2+ delivery system. SLA technology endows the scaffold with a three-dimensional tunnel structure to induce cell migration to the center of the bone defect. The calcium sulfate-Cu2+ delivery system was introduced to enhance the osteogenic activity of calcium silicate. Rapid degradation of calcium sulfate (CS) induces early osteogenesis in the three-dimensional tunnel structure. Calcium silicate (CSi) which degrades slowly provides mechanical support and promotes bone formation in bone defect sites for a long time. The gradient degradation of these two components is perfectly matched to the rate of repair in large bone defects. On the other hand, the calcium sulfate delivery system can regularly release Cu2+ in the temporal and spatial dimensions, exerting a long-lasting antimicrobial effect and promoting vascular growth. This powerful 3D-printed calcium silicate artificial bone which has rich osteogenic activity is a promising material for treating large bone defects and has excellent potential for clinical application.

Polypyridyl-based Co(III) complexes of vitamin B6 Schiff base for photoactivated antibacterial therapy.

Herein, five novel polypyridyl-based Co(III) complexes of Schiff bases, viz., [Co(dpa)(L1)]Cl (1), [Co(dpa)(L2)]Cl (2), [Co(L3)(L2)]Cl (3), [Co(L3)(L1)]Cl (4), and [Co(L4)(L1)]Cl (5), where dpa (dipicolylamine) = bis(2-pyridylmethyl)amine; H2L1 = (E)-2-((2-hydroxybenzylidene)amino)phenol; H2L2 = (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol; L3 = 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy); and L4 = 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy), were synthesized and characterized. Complexes 1, 3, and 4 were structurally characterized by single-crystal XRD, indicating an octahedral CoIIIN4O2 coordination core. The absorption bands of these complexes were observed in the visible range with a λmax at ∼430-485 nm. Complex 5 displayed an extra absorption band near 545 nm because of a ferrocene moiety. These absorptions in the visible region reflect the potential of the complexes to act as visible-light antimicrobial photodynamic therapy (aPDT) agents. All of these complexes showed reactive oxygen species (ROS)-mediated antibacterial effects against S. aureus (Gram-positive) and E. coli (Gram-negative bacteria) upon low-energy visible light (0.5 J cm-2, 400-700 nm) exposure. Additionally, 1-5 did not show any toxicity toward A549 (Human Lung adenocarcinoma) cells, reflecting their selective bacteria-killing abilities.

Near-infrared (NIR) imaging with indocyanine green (ICG) may assist in intraoperative decision making and improving surgical margin in bone and soft tissue tumor surgery.

BACKGROUND AND OBJECTIVES: Negative surgical margins are significant in improving patient outcomes. However, surgeons can only rely on visual and tactile information to identify tumor margins intraoperatively. We hypothesized that intraoperative fluorescence imaging with indocyanine green (ICG) could serve as an assistive technology to evaluate surgical margins and guide surgery in bone and soft tissue tumor surgery. METHODS: Seventy patients with bone and soft tissue tumors were enrolled in this prospective, non-randomized, single-arm feasibility study. All patients received intravenous indocyanine green (0.5 mg/kg) before surgery. Near-infrared (NIR) imaging was performed on in situ tumors, wounds, and ex vivo specimens. RESULTS: 60/70 tumors were fluorescent at NIR imaging. The final surgical margins were positive in 2/55 cases, including 1/40 of the sarcomas. Surgical decisions were changed in 19 cases by NIR imaging, and in 7/19 cases final pathology demonstrated margins were improved. Fluorescence analysis showed that the tumor-to-background ratio (TBR) of primary malignant tumors was higher than that of benign, borderline, metastatic, and tumors ≥5 cm in size had higher TBR than those <5 cm. CONCLUSIONS: ICG fluorescence imaging may be a beneficial technique to assist in surgical decision making and improving surgical margins in bone and soft tissue tumor surgery.

Application of Indocyanine Green Fluorescence Imaging in Assisting Biopsy of Musculoskeletal Tumors.

(1) Background: Biopsies are the gold standard for the diagnosis of musculoskeletal tumors. In this study, we aimed to explore whether indocyanine green near-infrared fluorescence imaging can assist in the biopsy of bone and soft tissue tumors and improve the success rate of biopsy. (2) Method: We recruited patients with clinically considered bone and soft tissue tumors and planned biopsies. In the test group, indocyanine green (0.3 mg/kg) was injected. After identifying the lesion, a near-infrared fluorescence camera system was used to verify the ex vivo specimens of the biopsy in real time. If the biopsy specimens were not developed, we assumed that we failed to acquire lesions, so the needle track and needle position were adjusted for the supplementary biopsy, and then real-time imaging was performed again. Finally, we conducted a pathological examination. In the control group, normal biopsy was performed. (3) Results: The total diagnosis rate of musculoskeletal tumors in the test group was 94.92% (56/59) and that in the control group was 82.36% (42/51). In the test group, 14 cases were not developed, as seen from real-time fluorescence in the core biopsy, and then underwent the supplementary biopsy after changing the puncture direction and the location of the needle channel immediately, of which 7 cases showed new fluorescence. (4) Conclusions: Using the near-infrared fluorescence real-time development technique to assist the biopsy of musculoskeletal tumors may improve the accuracy of core biopsy and help to avoid missed diagnoses, especially for some selected tumors.

Challenges in implementing GP clusters in Scotland: a qualitative study comparing the views of senior primary care stakeholders in 2016 with those in 2021.

BACKGROUND: Formation of GP clusters began in Scotland in April 2016 as part of a new Scottish GP contract. They aim to improve the care quality for local populations (intrinsic role) and the integration of health and social care (extrinsic role). AIM: To compare predicted challenges of cluster implementation in 2016 with reported challenges in 2021. DESIGN & SETTING: Qualitative study of senior national stakeholders in primary care in Scotland. METHOD: Qualitative analysis of semi-structured interviews with 12 senior primary care national stakeholders in 2016 (n = 6) and 2021 (n = 6). RESULTS: Predicted challenges in 2016 included balancing intrinsic and extrinsic roles, providing sufficient support, maintaining motivation and direction, and avoiding variation between clusters. Progress of clusters in 2021 was perceived as suboptimal and was reported to vary significantly across the country, reflecting differences in local infrastructure. Practical facilitation (data, administrative support, training, project improvement support, and funded time) and strategic guidance from the Scottish Government was felt to be lacking. GP engagement with clusters was felt to be hindered by the significant time and workforce pressures facing primary care. These barriers were considered as collectively contributing to cluster lead 'burnout' and loss of momentum, exacerbated by inadequate opportunities for shared learning between clusters across Scotland. Such barriers preceded, but were perpetuated by, the impact of the COVID-19 pandemic. CONCLUSION: Apart from the COVID-19 pandemic, many of the challenges reported by stakeholders in 2021 were predicted in 2016. Accelerating progress in cluster working will require renewed investment and support applied consistently across the country.

Evaluating primary care transformation: synthesis of findings from UK pilot project reviews.

BACKGROUND: Pilot 'new models' of primary care have been funded across the UK since 2015, through various national transformation funds. Reflections and syntheses of evaluation findings provide an additional layer of insight into 'what works' in transforming primary care. AIM: To identify good practice in policy design, implementation, and evaluation for primary care transformation. DESIGN & SETTING: A thematic analysis of existing pilot evaluations in England, Wales, and Scotland. METHOD: Ten studies presenting evaluations of three national pilot studies - the Vanguard programme in England, the Pacesetter programme in Wales, and the National Evaluation of New Models of Primary Care in Scotland - were thematically analysed, and findings synthesised in order to identify lessons learnt and good practice. RESULTS: Common themes emerged across studies in all three countries at project and policy level, which can support or inhibit new models of care. At project level, these included the following: working with all stakeholders, including communities and front-line staff; providing the time, space, and support necessary for the project to succeed; agreeing on clear objectives from the outset; and support for data collection, evaluation, and shared learning. At policy level, more fundamental challenges related to the parameters for pilot projects, in particular, the typically short-term nature of funding, with an expectation of results within 2-3 years. Changing expectations about outcome measures or project guidance part-way through project implementation was also identified as a key challenge. CONCLUSION: Primary care transformation requires coproduction and a rich, contextual understanding of local needs and complexities. However, a mismatch between policy objectives (care redesign to better meet patient needs) and policy parameters (short timeframes) is often a significant challenge to success.

Radial Sponges Facilitate Wound Healing by Promoting Cell Migration and Angiogenesis.

The topographic cues of wound dressings play important roles in regulating cellular behaviors, such as cellular migration and morphology, and are capable of providing a prolonged stimulus for promoting wound healing. However, 3D porous dressings that can guide wound healing from the periphery to the center are poorly studied. Herein, radial sponges with adjustable lamellar spacing and microridge spacing by ice templating are developed to facilitate wound healing. With denser lamellae and microridges, fibroblasts achieve a more orderly arrangement, a larger elongation, and a greater migration rate. Meanwhile, the elongated state enables human umbilical vein endothelial cells to vascularization. The faster healing rate and a higher degree of vascularization based on radial sponges are further demonstrated in full-thickness skin defects in rats. Taken together, radial sponges with the densest lamellae and microridges perform the best in guiding the wound from the periphery to the center of the repair environment. It is believed that the proposed structure here can be combined with various biochemical factors to provide dressings with functions.

Primary care transformation in Scotland: qualitative evaluation of the views of national senior stakeholders and cluster quality leads.

BACKGROUND: Primary care transformation in Scotland aims to improve population health, reduce health inequalities, and reduce GP workload. Two key strategies (formalised in April 2018 in the new Scottish GP contract [Scottish General Medical Services contract], although started in early 2016) are the expansion of the multidisciplinary team (MDT) and GP cluster working. AIM: To explore progress in the implementation of the GP contract in Scotland in terms of the MDT and cluster working. DESIGN AND SETTING: Qualitative study with key national primary care stakeholders (PCSs) (n = 6) and cluster quality leads (CQLs) in clusters serving urban high deprivation areas (n = 4), urban mixed areas (n = 4), and remote and rural areas (n = 4). METHOD: Semi-structured interviews with thematic analysis. RESULTS: There was general support for the initial aims of the new GP contract but all interviewees felt that progress on both MDT expansion and cluster working was slow, even before the pandemic. None of the CQLs (and few PCSs) felt that GP workload had reduced significantly, nor that the care of patients with complex needs had improved. Lack of time and poorly developed relationships were key barriers, as was a lack of relevant primary care data, and additional support (including guidance, administration, training, and protected time). CONCLUSION: Key PCSs and CQLs in different areas of Scotland report limited progress in primary care transformation, only partly related to the pandemic. There is a need for better workforce planning and support if the new GP contract is to succeed in transforming primary care in Scotland.

Research on Information Leakage Tracking Algorithms in Online Social Networks.

An online social network is a platform where people can communicate with friends, share information, speed up business development, and improve teamwork. A large amount of user privacy information existing in real social networks is leaked from person to person, and this issue has hardly been studied. With the rapid expansion of the network, the issue of privacy protection has received increasing attention. So far, many privacy protection methods including differential protection algorithms, encryption algorithms, access control strategies, and anonymization have been researched and applied. Information leakage means that the information shared by the user is disseminated or downloaded by his friends without the user's consent, and the transmission of private information will not be recorded. In order to track and find out the ways and methods of information leakage, this article adopts an unusual method, namely, the probability judgment based on trust. By screening the similarities between users, past information exchanges, and the topology of social networks, a trust model is established to evaluate and estimate the degree of trust between users. According to the rating information privacy of friends' trust, an information dissemination system is established, which can be applied to online social networking platforms to reduce the risk of information leakage, thereby ensuring the security of users' private information. At the same time, this paper expands the transmission system model without user authorization and proposes a fingerprint-based deterministic leak tracking algorithm.

Using self-determination theory in research and evaluation in primary care.

BACKGROUND: Multimorbidity (the co-existence of two or more long-term conditions within an individual) is a complex management challenge, with a very limited evidence base. Theories can help in the design and operationalization of complex interventions. OBJECTIVE: This article proposes self-determination theory (SDT) as a candidate theory for the development and evaluation of interventions in multimorbidity. METHODS: We provide an overview of SDT, its use in research to date, and its potential utility in complex interventions for patients with multimorbidity based on the new MRC framework. RESULTS: SDT-based interventions have mainly focused on health behaviour change in the primary prevention of disease, with limited use in primary care and chronic conditions management. However, SDT may be a useful candidate theory in informing complex intervention development and evaluation, both in randomized controlled trials and in evaluations of 'natural experiments'. We illustrate how it could be used multimorbidity interventions in primary care by drawing on the example of CARE Plus (a primary care-based complex intervention for patients with multimorbidity in deprived areas of Scotland). CONCLUSIONS: SDT may have utility in both the design and evaluation of complex interventions for multimorbidity. Further research is required to establish its usefulness, and limitations, compared with other candidate theories. PATIENT OR PUBLIC CONTRIBUTION: Our funded research programme, of which this paper is an early output, has a newly embedded patient and public involvement group of four members with lived experience of long-term conditions and/or of being informal carers. They read and commented on the draft manuscript and made useful suggestions on the text. They will be fully involved at all stages in the rest of the programme of research.

Progresses in Fluorescence Imaging Guidance for Bone and Soft Tissue Sarcoma Surgery.

R0 surgical resection is the preferred treatment for bone and soft tissue sarcoma. However, there is still a lack of precise technology that can visualize bone and soft tissue sarcoma during surgery to assist the surgeon in judging the tumor surgical boundary. Fluorescence imaging technology has been used in the diagnosis of cancer. It is a simple and essentially safe technique that takes no additional time during the operation. Intraoperative fluorescence imaging has potential application prospects in assisting the surgeons in judging the tumor boundary and improving the accuracy of surgical resection. This review mainly starts with clinical studies, animal experimentation, and newly designed probes of intraoperative fluorescence imaging of bone and soft tissue sarcoma, to appraise the application prospects of fluorescence imaging technology in bone and soft tissue sarcoma.

Association between genetic variants of microRNA-21 and microRNA-155 and systemic lupus erythematosus: A case-control study from a Chinese population.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common autoimmune disease, and its pathogenesis remains unclear. The alteration of genetic materials is believed to play a role in SLE development. This study evaluated the association between the genetic variants of microRNA-21 (miR-21) and microRNA-155 (miR-155) and SLE. METHODS: The SNaPshot genotyping method was used to detect the genotypes of selected SNPs in patients and controls. The expression of miR-21 and miR-155 was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The functional annotation and the biological effects of SNPs were assessed by HaploReg V4.1 and Regulome DB V2.0 software. The Hardy-Weinberg equilibrium test was used to gather statistics, and odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression. RESULTS: The distribution difference of TA genotype in rs767649 was observed (TA vs. T/T: OR = 0.68, 95%CI, 0.48-0.95, p = 0.026). There was a significant difference in the T/A + A/A (T/A + A/A vs. T/T: OR = 0.68, 95%CI, 0.49-0.94, p = 0.020). A significant difference in T allele distribution was found in the depressed complement of SLE (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026). There were significant differences in genetic variants of rs13137 between the positive and the negative SSB antibodies (Anti-SSB) (T vs. A: OR = 0.67, 95%CI, 0.47-0.95, p = 0.026; T/A + T/T vs. AA: OR = 2.23, 1.18-4.49, p = 0.013). The expression levels of miR-21 and miR-155 were significantly higher in patients than in controls (p < 0.001). CONCLUSIONS: This study provides novel insight that genetic variants of rs767649 and rs13137 are associated with susceptibility to SLE.

Basic Helix-Loop-Helix Transcription Factors AabHLH2 and AabHLH3 Function Antagonistically With AaMYC2 and Are Negative Regulators in Artemisinin Biosynthesis.

Plants have evolved sophisticated systems for regulating the biosynthesis of specialized phytochemicals. Artemisinin, which is a sesquiterpene lactone widely used in anti-malaria treatment, is produced by the Artemisia annua L. plant. However, the artemisinin content in A. annua is low and difficult to meet market demands. Studies have shown that artemisinin biosynthesis in A. annua has complex temporal and spatial specificity and is under tightly transcriptional regulation. However, the mechanism of transcriptional regulation of artemisinin biosynthesis remains unclear. In this study, we identified two MYC-type bHLH transcription factors (AabHLH2 and AabHLH3) as novel regulators of artemisinin biosynthesis. These bHLH TFs act as transcription repressors and function redundantly to negatively regulate artemisinin biosynthesis. Furthermore, AabHLH2 and AabHLH3 are nuclear proteins that bind to DNA elements with similar specificity to that of AaMYC2, but lack the conserved activation domain, suggesting that repression is achieved by competition for the same cis-regulatory elements. Together, our findings reveal a novel artemisinin biosynthesis regulatory network, provide new insight into how specialized metabolites are modulated in plants, and propose a model in which different bHLH TFs coordinated in regulating artemisinin production in the plant. Finally, this study provides some useful target genes for metabolic engineering of artemisinin production via CRISPR/Cas9 gene editing.