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BMC Geriatrics Jun 2024The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause...
BACKGROUND
The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture.
METHODS
A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death.
RESULTS
Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days.
CONCLUSIONS
Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.
Topics: Humans; Male; Female; Aged; Retrospective Studies; Hip Fractures; China; Aged, 80 and over; Risk Factors; Tertiary Care Centers; Risk Assessment
PubMed: 38909190
DOI: 10.1186/s12877-024-05159-y -
Cell Death & Disease Jun 2024TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary...
TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.
Topics: Cholangiocarcinoma; T-Box Domain Proteins; Humans; Animals; Mice; Bile Duct Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation
PubMed: 38909034
DOI: 10.1038/s41419-024-06839-8 -
Cancer Letters Jun 2024Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, survival for this stage of disease...
Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, survival for this stage of disease remains very low. Activating the immune system has incredible promise since it has the potential to be curative. However, immune checkpoint blockade (ICB) which works through T cells has been largely disappointing for metastatic breast cancer. One reason for this is a suppressive myeloid immune compartment that is unaffected by ICB. Cholesterol metabolism and proteins involved in cholesterol homeostasis play important regulatory roles in myeloid cells. Here, we demonstrate that NR0B2, a nuclear receptor involved in negative feedback of cholesterol metabolism, works in several myeloid cell types to impair subsequent expansion of regulatory T cells (T); T being a subset known to be highly immune suppressive and associated with poor therapeutic response. Within myeloid cells, NR0B2 serves to decrease many aspects of the inflammasome, ultimately resulting in decreased IL1β; IL1β driving T expansion. Importantly, mice lacking NR0B2 exhibit accelerated tumor growth. Thus, NR0B2 represents an important node in myeloid cells dictating ensuing T expansion and tumor growth, thereby representing a novel therapeutic target to re-educate these cells, having impact across different solid tumor types. Indeed, a paper co-published in this issue demonstrates the therapeutic utility of targeting NR0B2.
PubMed: 38908543
DOI: 10.1016/j.canlet.2024.217042 -
International Journal of Biological... Jun 2024While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites...
While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites are still debated. Neutral carbonyl groups and carboxylate groups are possible candidates. Also, while it is known that elastin degradation leads to calcification, it is unclear whether this is due to formation of new carboxylate groups or elastin fragmentation. In this work, we disentangle effects of carboxylate groups and particle size on elastin calcification; in doing so, we shed light on CaP mineralization sites on elastin. We find carboxylate groups accelerate calcification only in early stages; they mainly function as Ca ion chelation sites but not calcification sites. Their presence promotes formation (likely on Ca ions adsorbed on nearby carbonyl groups) of CaP minerals with high calcium-to-phosphate ratio as intermediate phases. Larger elastin particles calcify slower but reach similar amounts of CaP minerals in late stages; they promote direct formation of hydroxyapatite and CaP minerals with low calcium-to-phosphate ratio as intermediate phases. This work provides new perspectives on how carboxylate groups and elastin particle size influence calcification; these parameters can be tuned to study the mechanism of medial calcification and design drugs to inhibit the process.
PubMed: 38906359
DOI: 10.1016/j.ijbiomac.2024.133267 -
Polish Journal of Microbiology Jun 2024This study aimed to elucidate the influence of various culture medium components, including carbon sources, nitrogen sources, inorganic salts, suspension agents, and...
This study aimed to elucidate the influence of various culture medium components, including carbon sources, nitrogen sources, inorganic salts, suspension agents, and temperature, on the mycelial growth characteristics of . Employing single-factor experiments and response surface methodology within glass Petri dishes, the research identified that carrot powder, soybean powder, and ZnSO notably enhanced the proliferation of aerial mycelium, significantly augmenting the growth rate of mycelium. The resultant mycelium was observed to be dense, robust, and fluffy in texture. In particular, ZnSO markedly accelerated the mycelium growth rate. Furthermore, xanthan gum was found to effectively modulate the medium's viscosity, ensuring a stable suspension and facilitating nutrient equilibrium. The optimal cultivation temperature was determined to be 25°C, with mycelial growth ceasing below 5°C and mycelium perishing at temperatures exceeding 35°C. The optimal medium composition was established as follows: wheat starch 5 g/l, carrot powder 5 g/l, soybean powder 7.50 g/l, glucose 10 g/l, ZnSO 0.71 g/l, NHCl 0.68 g/l, xanthan gum 0.5 g/l, and agar 20 g/l. Under these optimized conditions, the mycelium of exhibited a rapid growth rate (1.04 ± 0.14 mm/day), characterized by a thick, dense, and well-developed structure. This investigation provides a theoretical foundation for the conservation, strain selection, and breeding of .
Topics: Mycelium; Culture Media; Temperature; Nitrogen; Carbon; Polysaccharides, Bacterial
PubMed: 38905279
DOI: 10.33073/pjm-2024-022 -
Regenerative Biomaterials 2024A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning...
A dressing patch made of radially oriented poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanofibers was successfully manufactured with a modified electrospinning strategy. The as-electrospun PHBV radially oriented nanofiber dressing patch exhibited uniform and bead-free nanofibrous morphology and innovative radially oriented arrangement, which was demonstrated to possess obviously improved mechanical property, increased surface hydrophilicity and enhanced biological properties compared to the PHBV nanofiber dressing patch control with traditionally randomly oriented pattern. Interestingly, it was found that the radially oriented pattern could induce the cell migration from the periphery to the center along the radially oriented nanofibers in a rapid manner. To further improve the biofunction of PHBV radially oriented nanofiber dressing patch, berberine (Beri, an isoquinoline alkaloid) with two different concentrations were encapsulated into PHBV nanofibers during electrospinning, which were found to present a sustained drug release behavior for nearly one month. Importantly, the addition of Beri could impart the dressing patch with excellent anti-inflammatory property by significantly inhibiting the secretion of pro-inflammatory factors of M1 macrophages, and also showed an additive influence on promoting the proliferation of human dermal fibroblasts (HDFs), as well as inhibiting the growth of , and compared with the Beri-free dressing patch. In the animal studies, the electrospun PHBV radially oriented nanofiber dressing patch loading with high Beri content was found to obviously accelerate the healing process of diabetic mouse full-thickness skin wound with shortened healing time (100% wound closure rate after 18 days' treatment) and improved healing quality (improved collagen deposition, enhanced re-epithelialization and neovascularization and increased hair follicles). In all, this study reported an innovative therapeutic strategy integrating the excellent physical cues of electrospun PHBV radially oriented nanofiber dressing patch with the multiple biological cues of Beri for the effective treatment of hard-to-heal diabetic wounds.
PubMed: 38903562
DOI: 10.1093/rb/rbae063 -
Cureus May 2024In addition to helping with wound healing, periapical surgery is performed to remove periapical disease. Concentrates of platelets have been applied extensively in...
In addition to helping with wound healing, periapical surgery is performed to remove periapical disease. Concentrates of platelets have been applied extensively in endodontics and other fields of regenerative medicine. A periapical inflammatory lesion was found in a 35-year-old male patient who complained of pain in the maxillary anterior region and displayed slight edema in the same area. The lesion was treated with periapical surgery utilizing advanced platelet-rich fibrin (A-PRF). Mesenchymal stem cell processes of proliferation and differentiation can be induced by several types of platelet concentrates. Growth factors are released at the application site by platelet-rich fibrin (PRF) for a minimum of seven days. The activity of osteoblasts is stimulated by growth factors and secreted cytokines. Furthermore, the release of growth factors promotes fibroblast migration, which quickens tissue regeneration. In addition to helping with wound healing, periapical surgery is performed to remove periapical disease. The synthesis of fibrin networks laden with platelets and growth factors is made possible by PRF, which is subsequently used to accelerate bone regeneration and, consequently, to improve bone formation. In this instance, the best possible bone regeneration and repair were accomplished. After 12 weeks, 24 weeks, and 36 weeks, the patient was brought back for follow-ups. He was found to be asymptomatic, and the radiograph showed considerable periapical healing with nearly enough bone production.
PubMed: 38903292
DOI: 10.7759/cureus.60742 -
Journal For Immunotherapy of Cancer Jun 2024Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During... (Review)
Review
Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and spatial transcriptomics have provided deep insights into the immunobiology of the tumor microenvironment. With this rapid clinical and scientific progress, the field of cancer immunotherapy is currently at a critical inflection point, with potential for exponential growth over the next decade. Recognizing this, the Society for Immunotherapy of Cancer convened a diverse group of experts in cancer immunotherapy representing academia, the pharmaceutical and biotechnology industries, patient advocacy, and the regulatory community to identify current opportunities and challenges with the goal of prioritizing areas with the highest potential for clinical impact. The consensus group identified seven high-priority areas of current opportunity for the field: mechanisms of antitumor activity and toxicity; mechanisms of drug resistance; biomarkers and biospecimens; unique aspects of novel therapeutics; host and environmental interactions; premalignant immunity, immune interception, and immunoprevention; and clinical trial design, endpoints, and conduct. Additionally, potential roadblocks to progress were discussed, and several topics were identified as cross-cutting tools for optimization, each with potential to impact multiple scientific priority areas. These cross-cutting tools include preclinical models, data curation and sharing, biopsies and biospecimens, diversification of funding sources, definitions and standards, and patient engagement. Finally, three key guiding principles were identified that will both optimize and maximize progress in the field. These include engaging the patient community; cultivating diversity, equity, inclusion, and accessibility; and leveraging the power of artificial intelligence to accelerate progress. Here, we present the outcomes of these discussions as a strategic vision to galvanize the field for the next decade of exponential progress in cancer immunotherapy.
Topics: Humans; Immunotherapy; Neoplasms; Societies, Medical
PubMed: 38901879
DOI: 10.1136/jitc-2024-009063 -
PloS One 2024The Global Investment Report 2023 revealed that after a sharp decline in 2020 and a strong rebound in 2021, global foreign direct investment (FDI) declined by 12 percent...
The Global Investment Report 2023 revealed that after a sharp decline in 2020 and a strong rebound in 2021, global foreign direct investment (FDI) declined by 12 percent to $1.3 trillion in 2022. However, in developing countries, FDI increased by 4% to $916 billion, a record share of more than 70% of global flows. The number of greenfield investment projects in developing countries increased by 37 percent and international project finance transactions by 5 percent. Foreign investment from China, the second largest recipient of foreign investment globally, increased by 5 percent. The service industry has become the mainstream industry in the global FDI structure. The global industry is accelerating its transformation to a "service-based economy," international FDI in productive service industries has become an essential means of industrial transfer in developed countries and a meaningful way to upgrade the industrial structure and high-quality development in emerging economies. As a representative province in central China, Hubei Province has unique advantages in human capital, factor cost, and market potential, which provide preferential conditions to attract foreign investment. This paper first introduced the concept of the productive service industry, based on the relevant statistical data from 2011 to 2022, focused on the current situation of foreign investment utilization in five major sub-sectors of the productive service industry in Hubei Province in the past ten years, and empirically investigated the impact of foreign investment utilization in five major sub-sectors of the productive service industry on the economic growth of Hubei Province, and obtained that the level of foreign investment attraction varied significantly among the regions in Hubei Province. The three productive service industries, namely transportation, storage and postal services, information transmission, software and information technology services, and financial services, played a significant role in the active attraction and optimal utilization of foreign capital and the economic development of Hubei Province. Based on this, it was proposed to build a market-oriented rule of law and internationalized business environment, improve the infrastructure construction in different regions of the province, focus on the training of professional talents for the development of productive service industries, and pay attention to the improvement of independent innovation capacity.
Topics: China; Investments; Industry; Humans; Developing Countries; Economic Development
PubMed: 38900766
DOI: 10.1371/journal.pone.0302494 -
BMC Plant Biology Jun 2024Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and...
Asparagus is a nutritionally dense stem vegetable whose growth and development are correlated with its quality and yield. To investigate the dynamic changes and underlying mechanisms during the elongation and growth process of asparagus stems, we documented the growth pattern of asparagus and selected stem segments from four consecutive elongation stages using physiological and transcriptome analyses. Notably, the growth rate of asparagus accelerated at a length of 25 cm. A significant decrease in the concentration of sucrose, fructose, glucose, and additional sugars was observed in the elongation region of tender stems. Conversely, the levels of auxin and gibberellins(GAs) were elevated along with increased activity of enzymes involved in sucrose degradation. A significant positive correlation existed between auxin, GAs, and enzymes involved in sucrose degradation. The ABA content gradually increased with stem elongation. The tissue section showed that cell elongation is an inherent manifestation of stem elongation. The differential genes screened by transcriptome analysis were enriched in pathways such as starch and sucrose metabolism, phytohormone synthesis metabolism, and signal transduction. The expression levels of genes such as ARF, GA20ox, NCED, PIF4, and otherswere upregulated during stem elongation, while DAO, GA2ox, and other genes were downregulated. The gene expression level was consistent with changes in hormone content and influenced the cell length elongation. Additionally, the expression results of RT-qPCR were consistent with RNA-seq. The observed variations in gene expression levels, endogenous hormones and sugar changes during the elongation and growth of asparagus tender stems offer valuable insights for future investigations into the molecular mechanisms of asparagus stem growth and development and provide a theoretical foundation for cultivation and production practices.
Topics: Asparagus Plant; Plant Stems; Plant Growth Regulators; Gene Expression Profiling; Gene Expression Regulation, Plant; Transcriptome; Sugars; Gibberellins
PubMed: 38898382
DOI: 10.1186/s12870-024-05277-0