Tissue-infiltrating alloreactive T cells require Id3 to deflect PD-1-mediated immune suppression during GVHD.

ABSTRACT: Persisting alloreactive donor T cells in target tissues are a determinant of graft-versus-host disease (GVHD), but the transcriptional regulators that control the persistence and function of tissue-infiltrating T cells remain elusive. We demonstrate here that Id3, a DNA-binding inhibitor, is critical for sustaining T-cell responses in GVHD target tissues in mice, including the liver and intestine. Id3 loss results in aberrantly expressed PD-1 in polyfunctional T helper 1 (Th1) cells, decreased tissue-infiltrating PD-1+ polyfunctional Th1 cell numbers, impaired maintenance of liver TCF-1+ progenitor-like T cells, and inhibition of GVHD. PD-1 blockade restores the capacity of Id3-ablated donor T cells to mediate GVHD. Single-cell RNA-sequencing analysis revealed that Id3 loss leads to significantly decreased CD28- and PI3K/AKT-signaling activity in tissue-infiltrating polyfunctional Th1 cells, an indicator of active PD-1/PD-L1 effects. Id3 is also required for protecting CD8+ T cells from the PD-1 pathway-mediated suppression during GVHD. Genome-wide RNA-sequencing analysis reveals that Id3 represses transcription factors (e.g., Nfatc2, Fos, Jun, Ets1, and Prdm1) that are critical for PD-1 transcription, exuberant effector differentiation, and interferon responses and dysfunction of activated T cells. Id3 achieves these effects by restraining the chromatin accessibility for these transcription factors. Id3 ablation in donor T cells preserved their graft vs tumor effects in mice undergoing allogeneic hematopoietic stem cell transplantation. Furthermore, CRISPR/Cas9 knockout of ID3 in human CD19-directed chimeric antigen receptor T cells retained their antitumor activity in NOD/SCID/IL2Rg-/- mice early after administration. These findings identify that ID3 is an important target to reduce GVHD, and the gene-editing program of ID3 may have broad implications in T-cell-based immunotherapy.

Hypoxic environment promotes angiogenesis and bone bridge formation by activating Notch/RBPJ signaling pathway in HUVECs.

After epiphyseal fracture, the epiphyseal plate is prone to ischemia and hypoxia, leading to the formation of bone bridge and deformity. However, the exact mechanism controlling the bone bridge formation remains unclear. Notch/RBPJ signaling axis has been indicated to regulate angiogenesis and osteogenic differentiation. Our study aims to investigate the mechanism of bone bridge formation after epiphyseal plate injury, and to provide a theoretical basis for new therapeutic approaches to prevent the bone bridge formation. The expression of DLL4 and RBPJ was significantly up-regulated in HUVECs after ischemia and hypoxia treatment. Notch/RBPJ pathway positively regulated the osteogenic differentiation of BMSCs. HUVECs can induce osteogenic differentiation of BMSCs under ischemia and hypoxia. Notch/RBPJ pathway is involved in the regulation of the trans-epiphyseal bridge formation. Notch/RBPJ in HUVECs is associated with osteogenic differentiation of BMSCs and may participate in the regulation of the bone bridge formation across the epiphyseal plate.

Cellular senescence in skeletal disease: mechanisms and treatment.

The musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and degenerative diseases, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. Skeletal diseases have a profound impact on the motor and cognitive abilities of the elderly, thus creating a major challenge for both global health and the economy. Cellular senescence is caused by various genotoxic stressors and results in permanent cell cycle arrest, which is considered to be the underlying mechanism of aging. During aging, senescent cells (SnCs) tend to aggregate in the bone and trigger chronic inflammation by releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved in regulating cellular senescence in bone and bone marrow microenvironments. Targeted SnCs alleviate age-related degenerative diseases. However, the association between senescence and age-related diseases remains unclear. This review summarises the fundamental role of senescence in age-related skeletal diseases, highlights the signalling pathways that mediate senescence, and discusses potential therapeutic strategies for targeting SnCs.

A scoping review of clinical reasoning research with Asian healthcare professionals.

Clinical reasoning is the thought process that guides practice. Although a plethora of clinical reasoning studies in healthcare professionals exists, the majority appear to originate from Western cultures. A scoping review was undertaken to examine clinical reasoning related research across Asian cultures. PubMed, SciVerse Scopus, Web of Science and Airiti Library databases were searched. Inclusion criteria included full-text articles published in Asian countries (2007 to 2019). Search terms included clinical reasoning, thinking process, differential diagnosis, decision making, problem-based learning, critical thinking, healthcare profession, institution, medical students and nursing students. After applying exclusion criteria, n = 240 were included in the review. The number of publications increased in 2012 (from 5%, n = 13 in 2011 to 9%, n = 22) with a steady increase onwards to 12% (n = 29) in 2016. South Korea published the most articles (19%, n = 46) followed by Iran (17%, n = 41). Nurse Education Today published 11% of the articles (n = 26), followed by BMC Medical Education (5%, n = 13). Nursing and Medical students account for the largest population groups studied. Analysis of the articles resulted in seven themes: Evaluation of existing courses (30%, n = 73) being the most frequently identified theme. Only seven comparative articles showed cultural implications, but none provided direct evidence of the impact of culture on clinical reasoning. We illuminate the potential necessity of further research in clinical reasoning, specifically with a focus on how clinical reasoning is affected by national culture. A better understanding of current clinical reasoning research in Asian cultures may assist curricula developers in establishing a culturally appropriate learning environment.

Real-Time Adsorption of Exo- and Endoglucanases on Cellulose: Effect of pH, Temperature, and Inhibitors.

Effective regulation of cellulase adsorption is key to improving the efficiencies of the two major bottlenecks of lignocellulose hydrolysis and cellulase recovery. In this work, we investigated the effect of inhibitors, pH, and temperature on the adsorption of exo- and endoglucanases (Cel7A and Cel7B, respectively) on cellulose using quartz crystal microgravimetry with dissipation. The addition of glucose and cellobiose can both inhibit the hydrolysis activity of Cel7A, whereas only cellobiose can inhibit that of Cel7B. Notably, the adsorption was favored by acidic conditions (pH ≤ 4.8) and low temperature, whereas alkaline conditions (pH 9 and 10) facilitated enzyme desorption, which is useful to guide the process of cellulase recovery. The adsorption and hydrolysis activity of Cel7A and Cel7B were both higher at 45 °C than at 25 °C. These findings pave the way to effective regulation of cellulase adsorption and thus improve lignocellulose conversion and cellulase recovery.

Dendrobium nobile Lindley and its bibenzyl component moscatilin are able to protect retinal cells from ischemia/hypoxia by dowregulating placental growth factor and upregulating Norrie disease protein.

BACKGROUND: Presumably, progression of developmental retinal vascular disorders is mainly driven by persistent ischemia/hypoxia. An investigation into vision-threatening retinal ischemia remains important. Our aim was to evaluate, in relation to retinal ischemia, protective effects and mechanisms of Dendrobium nobile Lindley (DNL) and its bibenzyl component moscatilin. The therapeutic mechanisms included evaluations of levels of placental growth factor (PLGF) and Norrie disease protein (NDP). METHODS: An oxygen glucose deprivation (OGD) model involved cells cultured in DMEM containing 1% O2, 94% N2 and 0 g/L glucose. High intraocular pressure (HIOP)-induced retinal ischemia was created by increasing IOP to 120 mmHg for 60 min in Wistar rats. The methods included electroretinogram (ERG), histopathology, MTT assay and biochemistry. RESULTS: When compared with cells cultured in DMEM containing DMSO (DMSO+DMEM), cells subjected to OGD and pre-administrated with DMSO (DMSO+OGD) showed a significant reduction in the cell viability and NDP expression. Moreover, cells that received OGD and 1 h pre-administration of 0.1 µM moscatilin (Pre-OGD Mos 0.1 µM) showed a significant counteraction of the OGD-induced decreased cell viability. Furthermore, compared with the DMSO+OGD group (44.54 ± 3.15%), there was significant elevated NDP levels in the Pre-OGD Mos 0.1 µM group (108.38 ± 29.33%). Additionally, there were significant ischemic alterations, namely reduced ERG b-wave, less numerous retinal ganglion cells, decreased inner retinal thickness, and reduced/enhanced amacrine's ChAT/Müller's GFAP or vimentin immunolabelings. Moreover, there were significantly increased protein levels of HIF-1α, VEGF, PKM2, RBP2 and, particularly, PLGF (pg/ml; Sham vs. Vehicle: 15.11 ± 1.58 vs. 39.53 ± 5.25). These ischemic effects were significantly altered when 1.0 g/Kg/day DNL (DNL1.0 + I/R or I/R+ DNL1.0) was applied before and/or after ischemia, but not vehicle (Vehicle+I/R). Of novelty and significance, the DNL1.0 action mechanism appears to be similar to that of the anti-PLGF Eylea [PLGF (pg/ml); DNL1.0 vs. Eylea+I/R: 19.93 ± 2.24 vs. 6.44 ± 0.60]. CONCLUSIONS: DNL and moscatilin are able to protect against retinal ischemic/hypoxic changes respectively by downregulating PLGF and upregulating NDP. Progression of developmental retinal vascular disorders such as Norrie disease due to persistent ischemia/hypoxia might be thus prevented.

Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis.

Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid-derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN-deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro-metastatic role of POSTN is largely limited to ER-negative breast cancer patients. Lysyl oxidase contributes to POSTN-promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mapping scoping reviews in neurosurgery: a scoping review protocol.

INTRODUCTION: The realm of neurosurgery is currently witnessing a surge in primary research, underscoring the importance of adopting evidence-based approaches. Scoping reviews, as a type of evidence synthesis, offer a broad perspective and have become increasingly vital for managing the ever-expanding body of research in swiftly evolving fields. Recent research has indicated a rising prevalence of scoping reviews in healthcare literature. In this context, the concept of a 'review of scoping reviews' has emerged as a means to offer a higher level synthesis of insights. However, the field of neurosurgery appears to lack a comprehensive integration of scoping reviews. Therefore, the objective of this scoping review is to identify and evaluate the extent of scoping reviews within neurosurgery, pinpointing research gaps and methodological issues to enhance evidence-based practices in this dynamic discipline. METHODS: The method framework of Arksey and O'Malley will be used to conduct the scoping review. A thorough literature search will be performed on Medline, Scopus and Web of Science to find eligible studies using the keywords related to neurosurgery, scoping review and its variants. Two reviewers will independently revise all of the full-text articles, extract data and evaluate the study extent. A narrative overview of the findings from included studies will be given. ETHICS AND DISSEMINATION: This review will involve secondary analysis of published literature, and therefore ethics approval is not required. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will be used to guide translation of findings. Results will be disseminated through peer-reviewed journals and presented in conferences via abstract and presentation.

Correction: Influence of alcohol provocation on medical professionals in Taiwan: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0264071.].

Collaborative clinical reasoning: a scoping review.

Background: Collaborative clinical reasoning (CCR) among healthcare professionals is crucial for maximizing clinical outcomes and patient safety. This scoping review explores CCR to address the gap in understanding its definition, structure, and implications. Methods: A scoping review was undertaken to examine CCR related studies in healthcare. Medline, PsychInfo, SciVerse Scopus, and Web of Science were searched. Inclusion criteria included full-text articles published between 2011 to 2020. Search terms included cooperative, collaborative, shared, team, collective, reasoning, problem solving, decision making, combined with clinical or medicine or medical, but excluded shared decision making. Results: A total of 24 articles were identified in the review. The review reveals a growing interest in CCR, with 14 articles emphasizing the decision-making process, five using Multidisciplinary Team-Metric for the Observation of Decision Making (MDTs-MODe), three exploring CCR theory, and two focusing on the problem-solving process. Communication, trust, and team dynamics emerge as key influencers in healthcare decision-making. Notably, only two articles provide specific CCR definitions. Conclusions: While decision-making processes dominate CCR studies, a notable gap exists in defining and structuring CCR. Explicit theoretical frameworks, such as those proposed by Blondon et al. and Kiesewetter et al., are crucial for advancing research and understanding CCR dynamics within collaborative teams. This scoping review provides a comprehensive overview of CCR research, revealing a growing interest and diversity in the field. The review emphasizes the need for explicit theoretical frameworks, citing Blondon et al. and Kiesewetter et al. The broader landscape of interprofessional collaboration and clinical reasoning requires exploration.

A new labdane diterpenoid from Scoparia dulcis improving pancreatic function against islets cell apoptotic by Bax/Bcl-2/Caspase-3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Scoparia dulcis has been identified as a significant ethnopharmacological substance in the Li, Zhuang, and Dai ethnic groups of China. Traditional medicine use S. dulcis to treat numerous illnesses, most notably diabetes. The considerable antidiabetic properties of this herbal remedy have been established by several clinical investigations and animal experiments. The islet is the intended target of S. dulcis, although the cause of its activity and mechanism for diabetes treatment is unclear. The diterpenoids from S. dulcis have been shown in the literature to have significant hypoglycemic efficacy and to protect islet cells in vitro. Diterpenoids may be the components of this herbal remedy that preserve islets, but further research is needed. AIM OF THE STUDY: This study was projected to investigate the new diterpenoid scoparicol E from S. dulcis and examined its islet-protective effect and the potential mechanism both in vitro and in vivo. METHODS: The structure of the novel diterpenoid scoparicol E was clarified by employing a wide range of spectroscopic methods. Using CCK-8 tests, cytotoxicity and antiapoptotic activity of scoparicol E were detected. Serum biochemical analysis and pathologic examination were performed to study the protective effect of scoparicol E against islet damage. The specific mechanism of action of scoparicol E was investigated through the mitochondrial membrane potential, Annexin V-FITC flow cytometry, and western blotting. RESULTS: Scoparicol E reduced MLD-STZ-induced hyperglycemia in mice and increased insulin and islet apoptosis. Scoparicol E effectively suppressed the Bax/Bcl-2/Caspase-3 pathway, according to the in vivo western blot investigation. Scoparicol E showed significant antiapoptotic action in vitro. We also showed that scoparicol E might prevent islet cells from dying by inhibiting the Bax/Bcl-2/Caspase-3 pathway. The Annexin V-FITC flow cytometry results revealed that MIN6 cell apoptosis was considerably decreased following scoparicol E intervention, showing anti-islet cell apoptosis action. Furthermore, the Caspase-3-mediated apoptosis pathway depends on cytochrome c and the potential of the mitochondrial membrane. Scoparicol E prevented the release of cytochrome c, restored the mitochondrial membrane potential, and prevented MIN6 cell apoptosis. CONCLUSION: We demonstrated the new diterpenoid scoparicol E could protect islet cells apoptosis by modulating the Bax/Bcl-2/Caspase-3 pathway.

A bibliometric analysis of literatures on uterine leiomyosarcoma in the last 20 years.

Background: Uterine leiomyosarcoma(uLMS) is a rare malignant tumor with low clinical specificity and poor prognosis.There are many studies related to uLMS, however, there is still a lack of metrological analyses with generalization. This study provides a bibliometric study of uLMS. Methods and materials: We chose the Web of Science (WoS) as our main database due to its extensive interdisciplinary coverage. We specifically focused on the literature from the last 20 years to ensure relevance and practicality. By utilizing the WOS core dataset and leveraging the R package "bibliometric version 4.1.0" and Citespace, we performed a comprehensive bibliometric analysis. This allowed us to pinpoint research hotspots and create visual representations, resulting in the retrieval of 2489 pertinent articles. Results: This literature review covers 2489 articles on uterine leiomyosarcoma (uLMS) from the past 20 years. Key findings include an average annual publication rate of 8.75, with a 6.07% yearly growth rate and an average citation count of 17.22. Core+Zone 2 sources contributed 1079 articles and 207 reviews, displaying a 4.98% annual growth rate. The analysis identified top journals, influential authors, and core sources, such as the prevalence of publications from the United States and the dominance of GYNECOLOGIC ONCOLOGY and HENSLEY ML. Bradford's Law and Lotka's Law highlighted core sources and author productivity, respectively. Thematic mapping and factorial analysis revealed research clusters, including etiology, diagnosis, treatment advancements, and surgical approaches, with prominent themes such as gemcitabine and docetaxel. Overall, this comprehensive analysis provides insights into uLMS literature trends and influential factors. Conclusion: This thorough bibliometric analysis, in its whole, illuminates the field's guiding principles while also revealing the subtle patterns within the uLMS literature. The knowledge gained here contributes to the current discussion in uLMS and related scientific fields and provides a solid basis for future research paths.

The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with an increased risk of diabetes-related complications. Hence, it is plausible that continuous positive airway pressure (CPAP) could have a favorable impact on these complications. We assessed the feasibility of conducting a randomized control trial in patients with type 2 diabetes and OSA over 2 years. METHODS: We conducted an open-label multicenter feasibility randomized control trial of CPAP vs no CPAP in patients with type 2 diabetes and OSA. Patients with resting oxygen saturation < 90%, central apnea index > 15 events/h, or Epworth Sleepiness Scale ≥ 11 were excluded. OSA was diagnosed using a multichannel portable device (ApneaLink Air, ResMed). The primary outcome measures were related to feasibility and the secondary outcomes were changes in various clinical and biochemical parameters related to diabetes outcomes. RESULTS: Eighty-three (40 CPAP vs 43 no CPAP) patients were randomly assigned, with a median (interquartile range) follow-up of 645 (545, 861) days. CPAP compliance was inadequate, with a median usage of approximately 3.5 hours/night. Early CPAP use predicted longer-term compliance. The adjusted analysis showed a possible favorable association between being randomly assigned to CPAP and several diabetes-related end points (chronic kidney disease, neuropathy, and quality of life). CONCLUSIONS: It was feasible to recruit, randomly assign, and achieve a high follow-up rate over 2 years in patients with OSA and type 2 diabetes. CPAP compliance might improve by a run-in period before randomization. A full randomized control trial is necessary to assess the observed favorable association between CPAP and chronic kidney disease , neuropathy, and quality of life in patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Registry: ISRCTN; Name: The impact of sleep disorders in patients with type 2 diabetes; URL: https://www.isrctn.com/ISRCTN12361838; Identifier: ISRCTN12361838. CITATION: Makhdom EA, Maher A, Ottridge R, et al. The impact of obstructive sleep apnea treatment on microvascular complications in patients with type 2 diabetes: a feasibility randomized controlled trial. J Clin Sleep Med. 2024;20(6):947-957.

Medical management of obesity.

Obesity is a global epidemic that has worsened over the past few decades. It is strongly associated with multiple health conditions, including type 2 diabetes mellitus, cardiovascular diseases, obstructive sleep apnoea, certain malignancies and has an increased mortality risk. The annual cost of obesity to the NHS is around £6 billion, projected to increase to just under £10 billion by 2050. In 2020-2021, obesity was cited as a factor in over 1 million hospital admissions. An early and pragmatic approach to the management of obesity would reduce obesity-associated multiple health conditions and result in cost savings for the NHS. Here, we discuss current management strategies for obesity, including dietary intervention, pharmacological therapies and optimisation, and bariatric surgery.

Energy and Infrared Radiation Characteristics of the Sandstone Damage Evolution Process.

The mechanical characteristics and mechanisms of rock failure involve complex rock mass mechanics problems involving parameters such as energy concentration, storage, dissipation, and release. Therefore, it is important to select appropriate monitoring technologies to carry out relevant research. Fortunately, infrared thermal imaging monitoring technology has obvious advantages in the experimental study of rock failure processes and energy dissipation and release characteristics under load damage. Therefore, it is necessary to establish the theoretical relationship between the strain energy and infrared radiation information of sandstone and to reveal its fracture energy dissipation and disaster mechanism. In this study, an MTS electro-hydraulic servo press was used to carry out uniaxial loading experiments on sandstone. The characteristics of dissipated energy, elastic energy, and infrared radiation during the damage process of sandstone were studied using infrared thermal imaging technology. The results show that (1) the transition of sandstone loading from one stable state to another occurs in the form of an abrupt change. This sudden change is characterized by the simultaneous occurrence of elastic energy release, dissipative energy surging, and infrared radiation count (IRC) surging, and it has the characteristics of a short duration and large amplitude variation. (2) With the increase in the elastic energy variation, the surge in the IRC of sandstone samples presents three different development stages, namely fluctuation (stage Ⅰ), steady rise (stage Ⅱ), and rapid rise (stage Ⅲ). (3) The more obvious the surge in the IRC, the greater the degree of local damage of the sandstone and the greater the range of the corresponding elastic energy change (or dissipation energy change). (4) A method of sandstone microcrack location and propagation pattern recognition based on infrared thermal imaging technology is proposed. This method can dynamically generate the distribution nephograph of tension-shear microcracks of the bearing rock and accurately evaluate the real-time process of rock damage evolution. Finally, this study can provide a theoretical basis for rock stability, safety monitoring, and early warning.

New aphidicolane diterpenoids with glucose consumption promoting and cell viability enhancing activities from Scoparia dulcis.

Two new aphidicolane diterpenoids, termed Scopadulinol A (1) and B (2), were obtained from whole plants of Scoparia dulcis. Their structures were elucidated by applying various spectroscopic techniques, including 1D- and 2D-NMR and HR-ESI-MS. The absolute configurations of 1 and 2 were determined by applying the calculated electronic circular dichroism (ECD). In addition, both compounds were tested for their effects on glucose consumption in HL-7702 cells and on palmitic acid (PA) induced viability in MIN6 cells at different concentrations. The results showed that they significantly promoted glucose consumption and attenuated the PA-induced decrease of cell viability. Additionally, 2 was tested to determine whether it could activate AMP-activated protein kinase (AMPK), but it showed no such effect at the tested dosage. These results indicated that the new compounds might promote glucose consumption through other pathways but not by activating AMPK. Collectively, we highlighted the isolation of two new aphidicolane diterpenoids from S. dulcis and found that they could promote glucose consumption and attenuate PA-induced decrease of cell viability.

Closure of Complex Wounds by a Simple Skin Stretching System Associated With Vacuum Sealing Drainage-Clinical Outcome of 34 Patients.

Management of complex wounds with large skin defects presents a real challenge for orthopedic or reconstructive surgeons. We developed a simple skin stretching system associated with vacuum sealing drainage to examine the efficiency and complication. A total of 34 patients with different types of complex wounds were retrospectively included from January 2015 to March 2021. All patients in the study were underwent the treatment by 2 stages. The method was used to the wounds from 4.71 to 169.65 cm2 with a median defect size of 25.13 cm2. The median time for wound closure was 11.5 days (range: 5-32 days), although the median absolute reduction was 2.08 cm2/day (range: 0.15-25.66 cm2/day). Depending on the site of the wounds, the cause of the wound, and the rate of max-width/max-length (W/L), these complex wounds could be separately divided into several groups. There were statistically significant differences in the median value of the above variables (P < .05 Kruskal-Wallis test). The results showed that different anatomical sites had different viscoelastic properties, the complex wounds caused by trauma were easier to close than caused by diabetic foot and the complex wounds in group A (W/L ＞ 0.5) were more difficult to close than in group B (W/L ≤ 0.5). No major complications were encountered in this study. In summary, the results of our study showed that the simple skin stretching system associated with vacuum sealing drainage was a safe approach for closure of complex wounds. Nevertheless, more attention should be paid to the viscoelasticity of the wounds to ensure closure and avoid undue complications when applying the method.

Matrix stiffening facilitates the collective invasion of breast cancer through the periostin-integrin mechanotransduction pathway.

Matrix rigidity is a critical contributor to tumor progression; however, whether and how matrix stiffness modulates the collective invasion of tumor cells remain unknown. Here we demonstrate that increased matrix stiffness activates YAP to promote the secretion of periostin (POSTN) in cancer-associated fibroblasts, which in turn augments the matrix rigidity of mammary glands and breast tumor tissues by facilitating collagen crosslinking. Moreover, decreased tissue stiffening resulted from the POSTN deficiency impairs peritoneal metastatic potential of orthotopic breast tumors. Increased matrix stiffness also promotes three-dimensional (3D) collective breast tumor cell invasion via multicellular cytoskeleton remodeling. POSTN triggers the integrin/FAK/ERK/Cdc42/Rac1 mechanotransduction pathway during 3D collective invasion of breast tumor. Clinically, high POSTN expression correlates with high collagen levels in breast tumors and cooperatively determines the metastatic recurrence potential in breast cancer patients. Collectively, these findings indicate that matrix rigidity promotes 3D collective invasion of breast tumor cells via the YAP-POSTN-integrin mechanotransduction signaling.

Medical Dispute Cases Caused by Errors in Clinical Reasoning: An Investigation and Analysis.

Studies that examine medical dispute cases (MDC) due to clinical reasoning (CR) are scarce in Taiwan. A retrospective analysis was undertaken to review MDC filed at four hospitals in Taiwan between 2011 and 2015. Cases were examined for the healthcare professionals involved, their relevance to CR errors, clinical specialties, and seniority. Seventy-eight MDC were identified and 57.7% of which were determined to be related to CR errors (n = 45). Among the 45 cases associated with CR errors, 82.2% (37) and 22.2% (10) were knowledge- and skill-related errors, respectively. The healthcare professionals with the most MDC were obstetrician-gynecologists (10/90, 11.1%), surgeons (8/90, 8.9%), and emergency physicians (7/90, 7.8%). The seniority of less than 5 years or lower had the highest number of attending physicians to be associated with MDC. In contrast, the highest seniority (>25 years) in the physician group and year 6 in the resident group are both shown with zero MDC. In our study, the larger hospitals had a significantly higher incidence of MDC compared to the smaller hospitals (Pearson Correlation Coefficient = 0.984, p = 0.016). An examination of MDC reveals the frequency and nature of medical errors in Taiwanese hospitals. Having identified that CR errors contributed a substantial fraction to the overall MDC, strategies to promote reasoning skills and hence reduce medico-legal issues help safeguard both patients and healthcare professionals.

Diagnostic Value and Prognostic Significance of Procalcitonin Combined with C-Reactive Protein in Patients with Bacterial Bloodstream Infection.

Objective: To study the clinical values and implications for the prognosis of procalcitonin (PCT) combined with C-reactive protein (hs-CRP) in patients with bacterial bloodstream infection. Methods: One hundred and twenty patients with infection hospitalized from Mar. 2020 to Jun. 2021 were chosen as subjects. All participants were tested for serum PCT, hs-CRP, and blood culture. According to the types of pathogenic bacteria, they were divided into the gram-negative bacteria bloodstream infection group (n = 53) and the gram-positive bacteria bloodstream infection group (n = 31). Depending on the prognostic outcome of the participants after 28 days, they were categorized into survival and fatality cohorts. The PCT and hs-CRP levels were compared to explore diagnostic value implications for the prognosis of the cases with bacterial bloodstream infection. Results: Serum PCT and hs-CRP values in the positive cohort were higher than those in the negative cohort. The levels of serum PCT and hs-CRP in pulmonary infection were higher than those in the group with negative cases, and the difference was statistically significant (P < 0.05). There were 27 gram-positive participants and 9 gram-negative cases in the positive cohort. The serum PCT value of gram-negative bacterial infection was greater than that of gram-positive bacterial infection. The value of serum PCT in the gram-negative bacterial infection group was higher than that in the gram-positive bacterial infection group, and the difference was statistically significant (P < 0.05). The areas under the curve (AUCs) of PCT, combination of hs-CRP and PCT, and hs-CRP were 0.946, 0.783, and 0.991, respectively. The combined examination of PCT and hs-CRP was the largest, PCT was the second, and hs-CRP was the lowest. These results indicated that the accuracy of combined detection of PCT and hs-CRP in the diagnostic bloodstream infection was the highest (0.991), followed by PCT (0.946) and the lowest (0.783). The PCT and hs-CRP levels of the survival cohort were lower than those in the death cohort. AUCs of PCT, hs-CRP and PCT, and hs-CRP were 0.848, 0.826, and 0.934, respectively. The combined examination of PCT and hs-CRP was the largest, followed by PCT and hs-CRP. The accuracy of the combination of PCT and hs-CRP was the highest (0.934), followed by PCT (0.848), and the diagnostic accuracy of hs-CRP was the lowest (0.826). Conclusion: There were significant differences in the levels of PCT and CRP between the gram-positive bacteria group and the gram-positive bacteria group. PCT and CRP have high diagnostic values in predicting the short-term prognosis of patients. PCT and CRP assist clinical diagnosis and guide treatment and play a positive role in early treatment and prognosis evaluation of patients.