A study on expression of GRP78 and CHOP in neutrophil endoplasmic reticulum and their relationship with neutrophil apoptosis in the development of sepsis.

We investigated the relationship between neutrophil apoptosis and endoplasmic reticulum stress (ERS) in sepsis and its mechanism. A prospective cohort study was conducted by recruiting a total of 58 patients with sepsis. Peripheral blood samples were collected on 1, 3, 5 and 7 days after admission to the ICU. The expressions of endoplasmic reticulum specific glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), apoptosis signal-regulating kinase 1 (ASK1), Bcl-2-like 11 (BIM), death receptor 5 (DR5), c-Jun N-terminal kinases (JNK) and p38 were detected by Western blot and PCR. The subcellular location of CHOP and GRP78 was observed by immunofluorescence analysis. Spearman correlation was used to analyze the correlation between the expression of chop protein and the apoptosis rate of peripheral blood neutrophils. Healthy volunteers in the same period were selected as the healthy control group. The expression of GRP78 protein was significantly elevated on the first day of ICU admission and showed a decreasing trend on the third, fifth and seventh day, but was significantly higher than the corresponding healthy control group. The expression of CHOP protein reached the highest level on the third day. The expression of chop protein in each group was significantly higher than that in the corresponding healthy control group. Immunofluorescence staining clearly showed that the CHOP protein accumulated in the nucleus, with an elevation in the intensity of GRP78. The neutrophil apoptosis rate of sepsis patients on the 1st, 3rd, 5th and 7th day of ICU stay was significantly higher than that of the healthy control group, with the highest apoptosis rate on the 3rd day, and then decreased gradually. CHOP protein expression level was significantly positively correlated with neutrophil apoptosis rate in sepsis patients. Endoplasmic reticulum stress occurs in neutrophils during the development of sepsis. GRP78 protein and CHOP protein may be involved in the pathological process of neutrophil apoptosis in sepsis.

Comparison of the Efficacy and Prognostic Factors of Endoscopic Submucosal Dissection with Different Procedures for Colorectal Neuroendocrine Tumors.

Objective: To compare the clinical efficacy, prognostic factors, and survival impact of endoscopic submucosal dissection (ESD) versus endoscopic submucosal resection (ESR) in patients with colorectal neuroendocrine tumors (NETs). Methods: This retrospective study analyzed 118 patients with colorectal NETs treated from January 2012 to December 2020. Patients were divided into the ESD group (n=59) and the ESR group (n=59) based on the surgical treatment method. We assessed the surgical efficacy, long-term survival, and factors influencing tumor recurrence using logistic regression analysis with clear criteria for group division. Results: En bloc resection, complete histological resection rates, and postoperative complications did not significantly differ between groups (P > .05). In the 33 patients with recurrence, those with tumor diameter < 10 mm, tumor grade G1, and negative resection margins were significantly fewer (P < .05). Logistic regression identified tumor diameter, grade, and resection margin status as significant predictors of recurrence (P < .05). There was no significant difference in distant metastasis, survival rates, and mortality between the groups (P > .05). Conclusions: ESD and ESR offer high clinical efficacy in treating colorectal NETs without significantly impacting prognosis or long-term survival. ESD, however, may be more suited for larger tumors due to its precise tissue removal capability. Future research should explore the long-term outcomes over 3 and 5 years to further validate these findings.

Screening and Analysis of SARS-CoV-2 Antibody Among Unvaccinated Blood Donors in Chongqing, China.

OBJECTIVE: To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody among unvaccinated voluntary blood donors in Chongqing, and to provide evidence for epidemic surveillance. METHODS: A total of 10,208 voluntary blood donors from January 5 to January 20, 2021, in the Chongqing area were collected, and the SARS-CoV-2 immunoglobulin (Ig) G and IgM antibodies were detected by chemiluminescence, and the differences of antibody-positive rate in different gender, age, ABO blood group, and different risk areas were analyzed. RESULTS: Among 10208 blood donors, 10 were found to be positive for SARS-COV-2 IgG antibody, giving a positivity rate of SARS-COV-2 IgG at 0.10%, and 29 were positive for SARS-CoV-2 IgM antibody, with a positivity rate of SARS-CoV-2 IgM at 0.28%. There was no statistical difference in the positive rate of antibody among different genders, ages, and ABO blood types, but it was related to the number of confirmed coronavirus disease 2019 (COVID-19) cases in each city. CONCLUSIONS: The SARS-CoV-2 seroprevalence rate in Chongqing was low and correlated with the number of confirmed COVID-19 cases.

Effect of thoracic paravertebral nerve block on delirium in patients after video-assisted thoracoscopic surgery: a systematic review and meta-analysis of randomized controlled trials.

Background: Nerve blocks are widely used in various surgeries to alleviate postoperative pain and promote recovery. However, the impact of nerve block on delirium remains contentious. This study aims to systematically evaluate the influence of Thoracic Paravertebral Nerve Block (TPVB) on the incidence of delirium in patients post Video-Assisted Thoracoscopic Surgery (VATS). Methods: We conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases in June 2023. The search strategy combined free-text and Medical Subject Headings (MeSH) terms, including perioperative cognitive dysfunction, delirium, postoperative cognitive dysfunction, paravertebral nerve block, thoracic surgery, lung surgery, pulmonary surgery, and esophageal/esophagus surgery. We utilized a random effects model for the analysis and synthesis of effect sizes. Results: We included a total of 9 RCTs involving 1,123 participants in our study. In VATS, TPVB significantly reduced the incidence of delirium on postoperative day three (log(OR): -0.62, 95% CI [-1.05, -0.18], p = 0.01, I2 = 0.00%) and postoperative day seven (log(OR): -0.94, 95% CI [-1.39, -0.49], p < 0.001, I2 = 0.00%). Additionally, our study indicates the effectiveness of TPVB in postoperative pain relief (g: -0.82, 95% CI [-1.15, -0.49], p < 0.001, I2 = 72.60%). Conclusion: The comprehensive results suggest that in patients undergoing VATS, TPVB significantly reduces the incidence of delirium and notably diminishes pain scores. Systematic review registration: CRD42023435528. https://www.crd.york.ac.uk/PROSPERO.

Identification of Periostin positive cell population during the long-term culture of mouse tendon-derived cells in late passage.

Tendon-derived cells exhibit phenotypic changes and gradually lose their proliferative capacity during serial passages in vitro. This study aimed to characterize the changes in the growth and stem cell characteristics of tendon-derived cells over a long-term culture. Mouse flexor digitorum profundus tendon-derived cells were obtained by enzymatic digestion and seeded at an initial density of 5,000/cm2. Cells were characterized by morphology, growth, senescence staining, trilineage differentiation assays, real-time PCR, immunocytochemistry, flow cytometry, and RNA sequencing analysis. Tendon-derived cells underwent a proliferative stage in the first three passages, followed by a gradual senescence. However, a novel cell population expressing Periostin (Postn+) emerged during the long-term culture from passages five to eight, which possessed a high rate of proliferation without significant senescence over successive passages. Compared to early passage cells, Postn+ cells exhibited enhanced osteogenic differentiation potential and attenuated chondrogenic differentiation potential, decreased expression of SSEA-1, Oct3/4, tenomodulin, scleraxis, CD90.2, CD73, CD105, Sca-1, and CD44, and increased expression of collagen III and CD34. RNA-sequencing analysis of Postn+ and early passage cells identified 908 differentially expressed genes, with ECM-receptor interaction and focal adhesion as the top pathways, and integrins as hub genes. This study highlights the dynamics of tendon-derived cells during serial passages. We identify a Postn+ cell population during long-term culture in late passages, with high proliferative ability and prominent osteogenic differentiation potential. Further investigations are needed to elucidate the origin and potential applications of Postn+ tendon-derived cells.

Treatment strategies and molecular mechanism of radiotherapy combined with immunotherapy in colorectal cancer.

Radiotherapy (RT) remodels the tumor immune microenvironment (TIME) and modulates the immune response to indirectly destroy tumor cells, in addition to directly killing tumor cells. RT combined with immunotherapy may significantly enhance the efficacy of RT in colorectal cancer by modulating the microenvironment. However, the molecular mechanisms by which RT acts as an immunomodulator to modulate the immune microenvironment remain unclear. Further, the optimal modalities of RT combined with immunotherapy for the treatment of colorectal cancer, such as the time point of combining RT and immunization, the fractionation pattern and dosage of radiotherapy, and other methods to improve the efficacy, are also being explored parallelly. To address these aspects, in this review, we summarized the mechanisms by which RT modulates TIME and concluded the progress of RT combined with immunization in preclinical and clinical trials. Finally, we discussed heavy ion radiation therapy and the efficacy of prediction markers and other immune combination therapies. Overall, combining RT with immunotherapy to enhance antitumor effects will have a significant clinical implication and will help to facilitate individualized treatment modalities.

Anteromedial Cortical Support in Reduction of Trochanteric Hip Fractures: From Definition to Application.

➤ The concept of anteromedial cortical support (AMCS) serves as valuable guidance for the intraoperative reduction of trochanteric hip fractures.➤ Positive medial cortical support (MCS) and positive or neutral anterior cortical support (ACS) are desirable. Some evidence has suggested that positive MCS is potentially superior to neutral MCS.➤ Experimental studies underscore the vital importance of the anteromedial wall and reveal why positive MCS potentially outperforms neutral MCS.➤ Incorporating the AMCS concept, the Chang reduction quality criteria (CRQC) are a reliable alternative approach to evaluate the reduction quality of trochanteric hip fractures.

Effect Analysis of the Venting Direction on Explosion Pressure in LPG Pipelines.

In order to study the effect of the venting direction on explosion pressure in liquefied petroleum gas pipelines, explosion accident scenarios are experimentally tested and numerically simulated in a pipeline model with different explosion venting directions. In addition, the effect characteristic is analyzed through the pressure field varying with time and peak pressure varying with the distance. Results show that the pressure in the vertical branch decreases sharply, while the pressure in the horizontal branch does not show an obvious decrease with explosion venting of the vertical branch. However, the pressure decreases obviously in both branches with explosion venting of the horizontal branch, and the biggest reduction of peak pressure of monitoring points is 73.55% compared with that without venting. In addition, large areas of negative pressure appear in both branches with explosion venting of the vertical branch; however, a large area of negative pressure area appears in the horizontal branch with explosion venting of the horizontal branch. What is more, the arrival time of peak pressure in the main pipe of the explosion pipeline is significantly reduced with explosion venting, which is caused by the different generation ways of peak pressure. The effect analysis result of the venting direction on explosion pressure could aid the optimal layout design of LPG pipelines with the location of venting and important facilities as well as with the selection of negative-pressure-resistant material and higher-accuracy sensors.

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The patient, a male newborn, was admitted to the hospital 2 hours after birth due to prematurity (gestational age 27+5 weeks) and respiratory distress occurring 2 hours postnatally. After admission, the infant developed fever and elevated C-reactive protein levels. On the fourth day after birth, metagenomic next-generation sequencing of cerebrospinal fluid indicated a positive result for Mycoplasma hominis (9 898 reads). On the eighth day, a retest of cerebrospinal fluid metagenomics confirmed Mycoplasma hominis (56 806 reads). The diagnosis of purulent meningitis caused by Mycoplasma hominis was established, and the antibiotic treatment was switched to moxifloxacin [5 mg/(kg·day)] administered intravenously for a total of 4 weeks. After treatment, the patient's cerebrospinal fluid tests returned to normal, and he was discharged as cured on the 76th day after birth. This article focuses on the diagnosis and treatment of neonatal Mycoplasma hominis purulent meningitis, introducing the multidisciplinary diagnosis and treatment of the condition in extremely preterm infants.

Novel insights into the protective effects of leonurine against acute kidney injury: Inhibition of ER stress-associated ferroptosis via regulating ATF4/CHOP/ACSL4 pathway.

Acute kidney injury (AKI) is a common and serious global health problem with high risks of mortality and the development of chronic kidney diseases. Leonurine is a unique bioactive component from Leonurus japonicus Houtt. and exerts antioxidant, antiapoptotic or anti-inflammatory properties. This study aimed to explore the benefits of leonurine on AKI and the possible mechanisms involved, with a particular foc on the regulation of ferroptosis and endoplasmic reticulum (ER) stress. Our results showed that leonurine exhibited prominent protective effects against AKI, as evidenced by the amelioration of histopathological alterations and reduction of renal dysfunction. In addition, leonurine significantly suppressed ferroptosis in AKI both in vivo and in vitro by effectively restoring ultrastructural abnormalities in mitochondria, decreasing ASCL4 and 4-HNE levels, scavenging reactive oxygen species (ROS), as well as increasing GPX4 and GSH levels. In parallel, leonurine also markedly mitigated ER stress via down-regulating PERK, eIF-2α, ATF4, CHOP and CHAC1. Further studies suggested that ER stress was closely involved in erastin-induced ferroptosis, and leonurine protected tubular epithelial cells in vitro by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway. Mechanistically, ATF4 silencing in vitro regulated CHOP and ACSL4 expressions, ultimately weakening both ER stress and ferroptosis. Notably, analyses of single-cell RNA sequencing data revealed that ATF4, CHOP and ASCL4 in renal tubular cells were all abnormally upregulated in patients with AKI compared to healthy controls, suggesting their contributions to the pathogenesis of AKI. Altogether, these findings suggest that leonurine alleviates AKI by inhibiting ER stress-associated ferroptosis via regulating ATF4/CHOP/ASCL4 signalling pathway, thus providing novel mechanisms for AKI treatment.

Endogenous H2S-activated Ag nanoparticles embedded in programmed DNA-cubes for specific visualization of colorectal cancer cells.

To avoid the unexpected aggregation and reduce the cytotoxicity of nanomaterials as optical probes in cell imaging applications, we propose a programmed DNA-cube as a carrier for silver nanoparticles (Ag NPs) to construct a specific hydrogen sulfide (H2S) responsive platform (Ag NP@DNA-cube) for diagnosing colorectal cancer (CRC) in this study. The DNA-cube maintains good dispersion of Ag NPs while providing excellent biocompatibility. Based on the characteristic overexpression of endogenous H2S in CRC cells, the Ag NPs are etched by H2S within target cells into silver sulfide quantum dots, thereby selectively illuminating the target cells. The Ag NP@DNA-cube exhibits a specific fluorescence response to CRC cells and achieves satisfactory imaging.

Functional versatility of Zur in metal homeostasis, motility, biofilm formation, and stress resistance in Yersinia pseudotuberculosis.

Zur (zinc uptake regulator) is a significant member of the Fur (ferric uptake regulator) superfamily, which is widely distributed in bacteria. Zur plays crucial roles in zinc homeostasis and influences cell development and environmental adaptation in various species. Yersinia pseudotuberculosis is a Gram-negative enteric that pathogen usually serves as a model organism in pathogenicity studies. The regulatory effects of Zur on the zinc transporter ZnuABC and the protein secretion system T6SS have been documented in Y. pseudotuberculosis. In this study, a comparative transcriptomics analysis between a ∆zur mutant and the wild-type (WT) strain of Y. pseudotuberculosis was conducted using RNA-seq. This analysis revealed global regulation by Zur across multiple functional categories, including membrane transport, cell motility, and molecular and energy metabolism. Additionally, Zur mediates the homeostasis not only of zinc but also ferric and magnesium in vivo. There was a notable decrease in 35 flagellar biosynthesis and assembly-related genes, leading to reduced swimming motility in the ∆zur mutant strain. Furthermore, Zur upregulated multiple simple sugar and oligopeptide transport system genes by directly binding to their promoters. The absence of Zur inhibited biofilm formation as well as reduced resistance to chloramphenicol and acidic stress. This study illustrates the comprehensive regulatory functions of Zur, emphasizing its importance in stress resistance and pathogenicity in Y. pseudotuberculosis. IMPORTANCE: Bacteria encounter diverse stresses in the environment and possess essential regulators to modulate the expression of genes in responding to the stresses for better fitness and survival. Zur (zinc uptake regulator) plays a vital role in zinc homeostasis. Studies of Zur from multiple species reviewed that it influences cell development, stress resistance, and virulence of bacteria. Y. pseudotuberculosis is an enteric pathogen that serves a model organism in the study of pathogenicity, virulence factors, and mechanism of environmental adaptation. In this study, transcriptomics analysis of Zur's regulons was conducted in Y. pseudotuberculosis. The functions of Zur as a global regulator in metal homeostasis, motility, nutrient acquisition, glycan metabolism, and nucleotide metabolism, in turn, increasing the biofilm formation, stress resistance, and virulence were reviewed. The importance of Zur in environmental adaptation and pathogenicity of Y. pseudotuberculosis was emphasized.

Impaired vestibular function associated with orthostatic hypotension in patients with multiple system atrophy.

BACKGROUND: Orthostatic hypotension (OH) is one of the most common symptoms in patients with multiple system atrophy (MSA). Vestibular system plays an important role in blood pressure regulation during orthostatic challenges through vestibular-sympathetic reflex. The current study aimed to investigate the relationship between vestibular function and OH in patients with MSA. METHODS: Participants with MSA, including 20 with OH (mean age, 57.55 ± 8.44 years; 7 females) and 15 without OH (mean age, 59.00 ± 8.12 years; 2 females) and 18 healthy controls (mean age, 59.03 ± 6.44 years; 8 females) were enrolled. Cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) tests were conducted to evaluate vestibular function. RESULTS: Patients with MSA presented with significantly higher rate of absent cVEMPs (57.1% vs 11.1%, p = 0.001) and oVEMPs (25.7% vs 0, p = 0.021) than controls. MSA patients with OH showed more absent cVEMPs (75.0% vs 11.1%, Bonferroni corrected p < 0.001) and oVEMPs (40.0% vs 0, Bonferroni corrected p = 0.003) than controls. Patients with OH also showed higher rate of absent cVEMPs than those without OH (33.3%, Bonferroni corrected p = 0.014). CONCLUSIONS: Our results demonstrated that impairment of vestibular function was associated with MSA, particularly in those with OH. Absent VEMPs may be a potential marker for MSA severity. Our findings suggest that impaired vestibular function is involved in OH development and may serve as an intervention target.

The Hsa_circ_0105558/miR-182-5p/ATF6 Cascade Affects H2O2-Triggered Oxidative Damage and Apoptosis of Human Lens Epithelial Cells.

Age-related cataract (ARC) is the prevalent cause of useful vision loss. Circular RNAs are related to ARC pathogenesis partly through their competing endogenous RNA (ceRNA) activity. Herein, we defined the action of hsa_circ_0105558 in hydrogen peroxide (H2O2)-driven apoptosis and oxidative damage in human lens epithelial SRA01/04 cells. Hsa_circ_0105558, microRNA (miR)-182-5p and activating transcription factor 6 (ATF6) were evaluated by a qRT-PCR or immunoblotting method. The hsa_circ_0105558/miR-182-5p and miR-182-5p/ATF6 relationships were predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assay. Reactive oxygen species level, glutathione peroxidase level, superoxide dismutase activity, and malondialdehyde level were measured using the matched assay kits. Hsa_circ_0105558 was upregulated in human ARC lens and H2O2-exposed SRA01/04 cells. Suppression of hsa_circ_0105558 attenuated H2O2-driven SRA01/04 cell apoptosis and oxidative damage. Hsa_circ_0105558 targeted miR-182-5p, and reduced miR-182-5p expression reversed the influence of hsa_circ_0105558 depletion on H2O2-driven oxidative damage and apoptosis. ATF6 was a target of miR-182-5p, and miR-182-5p-driven downregulation of ATF6 regulated cell oxidative damage and apoptosis under H2O2 insult. Moreover, hsa_circ_0105558 functioned as a ceRNA to post-transcriptionally control ATF6 expression through miR-182-5p competition. Our study demonstrates that hsa_circ_0105558 modulates SRA01/04 cell oxidative damage and apoptosis under H2O2 insult through the miR-182-5p/ATF6 cascade.

Modulating the ferroelectric phases in cholesteryl-based organic compounds with perfluoroalkyl tail engineering.

Here, we synthesized a series of cholesteryl-based compounds, whose phases and their transformation can be modulated by temperature and the chain length of the fluoroalkyl moieties. To our knowledge, this is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.

Recent advances in shape memory polymeric nanocomposites for biomedical applications and beyond.

Shape memory polymers (SMPs), which initiate shape transformation in response to environmental stimuli, have attracted significant attention in both academic research and technological innovation. The combination of functional nanomaterials and SMPs has led to the emergence of a variety of shape memory polymeric nanocomposites (SMPNs) with multifunctional properties. This has injected new vitality and vigor into fields such as tissue engineering, biomedicine, optical sensing, aerospace and mechanical engineering. In this review article, we present a brief introduction to the fundamentals of SMPs and SMPNs, followed by a discussion of the recent advances in their multifunctional applications in biomedical manufacturing, drug delivery devices, mechanical sensing, micro-engines, etc. The opportunities and challenges in the future development of SMPs are also discussed.

Tumor hyperthermia research progress and application prospect in tumoroids (Review).

Tumor hyperthermia is the fifth tumor treatment method after surgery, chemotherapy, radiotherapy and biological therapy, and is also one of the important adjuvant treatment methods for tumors. Hyperthermia can not only directly eliminate tumor cells, but also stimulate the antitumor immune response of the body, and improve the sensitivity of tumor tissues to radiotherapy and chemotherapy. An organoid is a tissue-specific cell cluster formed by 3D culture of various types of cells derived from target organ stem cells, which can reproduce the functions of target organs in vivo. At present, the research models of hepatocellular carcinoma (HCC) in vitro are mainly 2D culture cell line models, and there is no clinical report on tumor hyperthermia using HCC tumoroids. It was hypothesized that this will be a promising research direction.

Striatal and Extrastriatal Monoaminergic Disruption in Progressive Supranuclear Palsy.

BACKGROUND: As a biomarker targeting vesicular monoamine transporter 2 (VMAT2), 18 F-9-fluoropropyldihydrotetrabenazine (18 F-FP-DTBZ) positron emission tomography (PET) is highly accurate in diagnosing Parkinson's disease (PD) and assessing its severity. However, evidence is insufficient in patients with progressive supranuclear palsy (PSP). OBJECTIVE: We evaluated the striatal and extrastriatal monoaminergic disruption of PSP and differences in patterns between patients with PSP, PD, and healthy controls (HCs) using 18 F-FP-DTBZ PET, as well as its correlations with the clinical characteristics of PSP. METHODS: We recruited 58 patients with PSP, 23 age- and duration-matched patients with PD, as well as 17 HCs. Patients were scanned using 18 F-FP-DTBZ PET/computed tomography, and images were spatially normalized and analyzed based on the volume of interest. RESULTS: VMAT2 binding differed significantly in the striatum and substantia nigra among the groups (P < 0.001). A more severe disruption in the caudate was noted in the PSP group (P < 0.001) than in the PD group. However, no differences were found in the nucleus accumbens, hippocampus, amygdala, or raphe between the PD and PSP groups. Within the PSP group, striatal VMAT2 binding was significantly associated with the fall/postural stability subscore of the PSP Rating Scale, especially in the putamen. Furthermore, VMAT2 binding was correlated with Mini-Mental State Examination or Montreal Cognitive Assessment in the hippocampus. CONCLUSIONS: Caudate disruptions showed prominent differences among the groups. VAMT2 binding in the striatum and hippocampus reflects the severity of fall/postural stability and cognition, respectively. © 2024 International Parkinson and Movement Disorder Society.