Clinical study of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammatory indicators that can be used to predict the severity and prognosis of various diseases. We categorize acute pancreatitis by etiology into acute biliary pancreatitis (ABP) and hypertriglyceridemia-induced acute pancreatitis (HTGP). AIM: To investigate the clinical significance of NLR and PLR in assessing persistent organ failure (POF) in HTGP and ABP. METHODS: A total of 1450 patients diagnosed with acute pancreatitis (AP) for the first time at Shanxi Bethune Hospital between January 2012 and January 2023 were enrolled. The patients were categorized into two groups according to the etiology of AP: ABP in 530 patients and HTGP in 241 patients. We collected and compared the clinical data of the patients, including NLR, PLR, and AP prognostic scoring systems, within 48 h of hospital admission. RESULTS: The NLR (9.1 vs 6.9, P < 0.001) and PLR (203.1 vs 160.5, P < 0.001) were significantly higher in the ABP group than in the HTGP group. In the HTGP group, both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score ≥ 3. Likewise, in the ABP group, NLR and PLR were significantly elevated in patients with severe AP, modified computed tomography severity index score ≥ 4, Japanese Severity Score ≥ 3, and modified Marshall score ≥ 2. Moreover, NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP groups. CONCLUSION: NLR and PLR vary between ABP and HTGP, are strongly associated with AP prognostic scoring systems, and have predictive potential for the occurrence of POF in both ABP and HTGP.

Clinical efficacy of Gamma Knife® combined with transarterial chemoembolization and immunotherapy in the treatment of primary liver cancer.

BACKGROUND: This study was designed to investigate the clinical efficacy and safety of Gamma Knife® combined with transarterial chemoembolization (TACE) and immunotherapy in the treatment of primary liver cancer. AIM: To investigate the clinical efficacy and safety of Gamma Knife® combined with TACE and immune-targeted therapy in the treatment of primary liver cancer. METHODS: Clinical data from 51 patients with primary liver cancer admitted to our hospital between May 2018 and October 2022 were retrospectively collected. All patients underwent Gamma Knife® treatment combined with TACE and immunotherapy. The clinical efficacy, changes in liver function, overall survival (OS), and progression-free survival (PFS) of patients with different treatment responses were evaluated, and adverse reactions were recorded. RESULTS: The last follow-up for this study was conducted on October 31, 2023. Clinical evaluation of the 51 patients with primary liver cancer revealed a partial response (PR) in 27 patients, accounting for 52.94% (27/51); stable disease (SD) in 16 patients, accounting for 31.37% (16/51); and progressive disease (PD) in 8 patients, accounting for 15.69% (8/51). The objective response rate was 52.94%, and the disease control rate was 84.31%. Alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alpha-fetoprotein isoform levels decreased after treatment compared with pretreatment (all P = 0.000). The median OS was 26 months [95% confidence interval (95%CI): 19.946-32.054] in the PR group and 19 months (95%CI: 14.156-23.125) in the SD + PD group, with a statistically significant difference (P = 0.015). The median PFS was 20 months (95%CI: 18.441-34.559) in the PR group and 12 months (95%CI: 8.745-13.425) in the SD + PD group, with a statistically significant difference (P = 0.002). Common adverse reactions during treatment included nausea and vomiting (39.22%), thrombocytopenia (27.45%), and leukopenia (25.49%), with no treatment-related deaths reported. CONCLUSION: Gamma Knife® combined with TACE and immune-targeted therapy is safe and effective in the treatment of primary liver cancer and has a good effect on improving the clinical benefit rate and liver function of patients.

The Role of the Gut Microbiome in Neuroinflammation and Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating adverse effects caused by chemotherapy drugs such as paclitaxel, oxaliplatin and vincristine. It is untreatable and often leads to the discontinuation of cancer therapy and a decrease in the quality of life of cancer patients. It is well-established that neuroinflammation and the activation of immune and glial cells are among the major drivers of CIPN. However, these processes are still poorly understood, and while many chemotherapy drugs alone can drive the activation of these cells and consequent neuroinflammation, it remains elusive to what extent the gut microbiome influences these processes. In this review, we focus on the peripheral mechanisms driving CIPN, and we address the bidirectional pathways by which the gut microbiome communicates with the immune and nervous systems. Additionally, we critically evaluate literature addressing how chemotherapy-induced dysbiosis and the consequent imbalance in bacterial products may contribute to the activation of immune and glial cells, both of which drive neuroinflammation and possibly CIPN development, and how we could use this knowledge for the development of effective treatment strategies.

Degradation of perineuronal nets in the medial prefrontal cortex promotes extinction and reduces reinstatement of methamphetamine-induced conditioned place preference in female mice.

The high rate of relapse to compulsive methamphetamine (MA)-taking and seeking behaviors after abstinence constitutes a major obstacle to the treatment of MA addiction. Perineuronal nets (PNNs), essential components of the extracellular matrix, play a critical role in synaptic function, learning, and memory. Abnormalities in PNNs have been closely linked to a series of neurological diseases, such as addiction. However, the exact role of PNNs in MA-induced related behaviors remains elusive. Here, we established a MA-induced conditioned place preference (CPP) paradigm in female mice and found that the number and average optical density of PNNs increased significantly in the medial prefrontal cortex (mPFC) of mice during the acquisition, extinction, and reinstatement stages of CPP. Notably, the removal of PNNs in the mPFC via chondroitinase ABC (ChABC) before extinction training not only facilitated the extinction of MA-induced CPP and attenuated the relapse of extinguished MA preference but also significantly reduced the activation of c-Fos in the mPFC. Similarly, the ablation of PNNs in the mPFC before reinstatement markedly lessened the reinstatement of MA-induced CPP, which was accompanied by the decreased expression of c-Fos in the mPFC. Collectively, our results provide more evidence for the implication of degradation of PNNs in facilitating extinction and preventing relapse of MA-induced CPP, which indicate that targeting PNNs may be an effective therapeutic option for MA-induced CPP memories.

Detection of atrial fibrillation using a nonlinear Lorenz Scattergram and deep learning in primary care.

BACKGROUND: Atrial fibrillation (AF) is highly correlated with heart failure, stroke and death. Screening increases AF detection and facilitates the early adoption of comprehensive intervention. Long-term wearable devices have become increasingly popular for AF screening in primary care. However, interpreting data obtained by long-term wearable ECG devices is a problem in primary care. To diagnose the disease quickly and accurately, we aimed to build AF episode detection model based on a nonlinear Lorenz scattergram (LS) and deep learning. METHODS: The MIT-BIH Normal Sinus Rhythm Database, MIT-BIH Arrhythmia Database and the Long-Term AF Database were extracted to construct the MIT-BIH Ambulatory Electrocardiograph (MIT-BIH AE) dataset. We converted the long-term ECG into a two-dimensional LSs. The LSs from MIT-BIH AE dataset was randomly divided into training and internal validation sets in a 9:1 ratio, which was used to develop and internally validated model. We built a MOBILE-SCREEN-AF (MS-AF) dataset from a single-lead wearable ECG device in primary care for external validation. Performance was quantified using a confusion matrix and standard classification metrics. RESULTS: During the evaluation of model performance based on the LS, the sensitivity, specificity and accuracy of the model in diagnosing AF were 0.992, 0.973, and 0.983 in the internal validation set respectively. In the external validation set, these metrics were 0.989, 0.956, and 0.967, respectively. Furthermore, when evaluating the model's performance based on ECG records in the MS-AF dataset, the sensitivity, specificity and accuracy of model diagnosis paroxysmal AF were 1.000, 0.870 and 0.876 respectively, and 0.927, 1.000 and 0.973 for the persistent AF. CONCLUSIONS: The model based on the nonlinear LS and deep learning has high accuracy, making it promising for AF screening in primary care. It has potential for generalization and practical application.

Unraveling the intricacies of glycosaminoglycan biosynthesis: Decoding the molecular symphony in understanding complex polysaccharide assembly.

Glycosaminoglycans (GAGs) are extensively utilized in clinical, cosmetic, and healthcare field, as well as in the treatment of thrombosis, osteoarthritis, rheumatism, and cancer. The biological production of GAGs is a strategy that has garnered significant attention due to its numerous advantages over traditional preparation methods. In this review, we embark on a journey to decode the intricate molecular symphony that orchestrates the biosynthesis of glycosaminoglycans. By unraveling the complex interplay of related enzymes and thorough excavation of the intricate metabolic cascades involved, GAGs chain aggregation and transportation, which efficiently and controllably modulate GAGs sulfation patterns involved in biosynthetic pathway, we endeavor to offer a thorough comprehension of how these remarkable GAGs are intricately assembled and pushes the boundaries of our understanding in GAGs biosynthesis.

Oral edaravone ameliorates behavioral deficits and pathologies in a valproic acid-induced rat model of autism spectrum disorder.

Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Safety of one 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage after uniportal video-assisted thoracoscopic surgery pneumonectomy.

OBJECTIVES: Uniportal video-assisted thoracoscopic surgery pneumonectomy (U-VATS-P) is feasible and safe from a perioperative standpoint. How to choose the proper chest tube and drainage method is important in enhanced recovery after surgery (ERAS) protocols. In this study, we aimed to assess the safety of one 8.5-Fr (1Fr = 0.333 mm) pigtail catheter for postoperative continuous open gravity drainage after U-VATS-P. METHODS: We retrospectively reviewed a single surgeon's experience with U-VATS-P for lung cancer from May 2016 to September 2022. Patients were managed with one 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage after U-VATS-P. The clinical characteristics and perioperative outcomes of the patients were retrospectively analyzed. RESULTS: In total, 77 patients had one 8.5-Fr pigtail catheter placed for postoperative continuous open gravity drainage after U-VATS-P for lung cancer. The mean age was 60.9±7.39 (40-76) years; The mean FEV1 was 2.1±0.6 (l/s), and the mean FEV1% was 71.2±22.7. The median operative time was 191.38±59.32 min; the mean operative hemorrhage was 109.46±96.56 ml; the mean duration of postoperative chest tube drainage was 6.80±2.33 days; the mean drainage volumes in the first three days after operation were 186.31±50.97, 321.97±52.03, and 216.44±35.67 ml, respectively; and the mean postoperative hospital stay was 7.90±2.58 days. No patient experienced complications resulting from chest tube malfunction. Ten patients experienced minor complications. One patient with nonlife-threatening empyema and bronchopleural fistula required short rehospitalization for anti-inflammatory therapy and reintubation. Three patients with chylothorax were treated with intravenous nutrition. Four patients had atrial fibrillation that was controlled by antiarrhythmic therapy. Two patients had more thoracic hemorrhagic exudation after the operation, which was found in time and was cured effectively, so they were discharged from the hospital uneventfully after early hemostatic therapy and nutritional support. CONCLUSIONS: All patients in this study received early postoperative rehabilitation, and the rate of relevant complications was low. We therefore recommend a single 8.5-Fr pigtail catheter for postoperative continuous open gravity drainage as an effective, safe and reliable drainage method for the management of U-VATS-P.

Death-Associated Protein-1 Plays a Role in the Reproductive Development of Nilaparvata lugens and the Transovarial Transmission of Its Yeast-Like Symbiont.

Death-associated protein-1 (DAP-1) plays a crucial role in cell growth, migration, autophagy, and apoptosis in mammals. However, its function in insects remains unclear. In the present study, we cloned and identified Nilaparvata lugens DAP-1 (NlDAP-1). NlDAP-1 was expressed during all developmental stages and in all tissues of N. lugens, being particularly higher in the ovaries of female adults. RNAi with double-stranded NlDAP-1 RNA significantly inhibited the expression of NlDAP-1, leading to premature death (dying seven days earlier), delayed ovarian development, and fewer offspring (76.7% reduction in eggs with 77.4% reduction in egg hatching rate). Additionally, an immunofluorescence experiment showed that NlDAP-1 was highly expressed when yeast-like symbionts (YLSs) entered N. lugens oocytes, and inhibiting the expression of NlDAP-1 disturbed the process; the RNAi of NlDAP-1 caused a 34.9% reduction in the YLSs that entered oocytes. These results indicate that NlDAP-1 plays a crucial role in the reproductive development of N. lugens and the transovarial transmission of its YLSs.

U-shaped association between serum calcium and in-hospital mortality in diabetes patients with congestive heart failure: a cohort study.

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.

Biomechanism of abnormal stress on promoting osteoarthritis of temporomandibular joint through Piezo1 ion channel.

OBJECTIVE: This study aimed to investigate whether flow fluid shear stress (FFSS)-mediated signal transduction affects the function of Piezo1 ion channel in chondrocyte and to further explore the role of mechanical overloading in development of temporomandibular joint osteoarthritis (TMJ OA). METHODS: Immunohistochemical staining was used to determine the expression of Piezo1 in TMJ OA tissue collected from rat unilateral anterior crossbite (UAC) models. Chondrocytes harvested from normal adult SD rats were treated with FFSS (0, 4, 8, 12 dyn/cm2) in vitro. Immunofluorescent staining, real-time polymerase chain reaction, western blotting, flow cytometry and phalloidin assay were performed to detect the changes of cellular morphology as well as the expression of Piezo1 and certain pro-inflammatory and degradative factors in chondrocyte. RESULTS: Immunohistochemical analysis revealed that significantly increased Piezo1 expression was associated with UAC stimulation (p < .05). As applied FFSS escalated (4, 8 and 12 dyn/cm2), the expression levels of Piezo1, ADAMTS-5, MMP-13 and Col-X gradually increased, compared with the non-FFSS group (p < .05). Administering Piezo1 ion channel inhibitor to chondrocytes beforehand, it was observed that expression of ADAMTS-5, MMP-13 and Col-X was substantially decreased following FFSS treatment (p < .05) and the effect of cytoskeletal thinning was counteracted. The activated Piezo1 ion channel enhanced intracellular Ca2+ excess in chondrocytes during abnormal mechanical stimulation and the increased intracellular Ca2+ thinned the cytoskeleton of F-actin. CONCLUSIONS: Mechanical overloading activates Piezo1 ion channel to promote pro-inflammation and degradation and to increase Ca2+ concentration in chondrocyte, which may eventually result in TMJ OA.

[Impacts of Urban Form on Carbon Emissions Under the Goal of Carbon Emission Peak and Carbon Neutrality: A Case Study of the Yangtze River Economic Belt].

Clarifying the mechanism of influence of urban form on carbon emissions is an important prerequisite for achieving urban carbon emission reduction. Taking the Yangtze River Economic Belt as an example, this study elaborated on the general mechanism of urban form on carbon emissions, used multi-source data to quantitatively evaluate the urban form, and explored the impacts of urban form indicators on carbon emissions from 2005 to 2020 at global and sub-regional scales with the help of spatial econometric models and geodetector, respectively. The results showed that:① The carbon emissions of the Yangtze River Economic Belt increased from 2 365.31 Mt to 4 230.67 Mt, but the growth rate gradually decreased. Its spatial distribution pattern was bipolar, with high-value areas mainly distributed in core cities such as Shanghai and Chongqing and low-value areas concentrated in the western regions of Sichuan and Yunnan. ② The area of construction land in the study area expanded over the past 15 years, but the population density of construction land had been decreasing. The degree of urban fragmentation was decreasing, and the difference between cities was also progressively narrowing. The average regularity of urban shape improved, and the compactness increased significantly. ③ All indicators of urban scale had significant positive effects on carbon emissions at the global scale, urban fragmentation had a significant negative effect in 2005, and the effective mesh size (MESH) indicator of urban compactness showed a significant negative correlation with carbon emissions in the study period. ④ Total class area, patch density, and effective mesh size had the most significant impacts on carbon emissions in upstream cities. Effective mesh size, mean perimeter-area ratio, and total class area had higher influences in midstream cities. Effective mesh size, percentage of like adjacencies, and largest patch index were the key factors to promote carbon reduction in downstream cities. Cities in different regions should comprehensively consider the impacts of various urban form indicators on carbon emissions and then optimize their urban form to promote sustainable development.

Psychological health in Palliative Care: Thematic analysis of a psychiatrist's and an art therapist's clinical reflexive journals.

BACKGROUND: Patients receiving palliative care often face psychological distress, which can be challenging for clinicians to manage. Therefore, reflexive and visual journaling can be used as powerful techniques for clinician selfreflection and personal development. These journals are a form of practice wisdom, providing insights into psychological health in palliative care. AIM: This study aims to describe how patients receiving palliative care experience psychological health, explore the meaning of a palliative care clinician's work and contribute to the understanding of psychological health in palliative care through the reflexive and visual journals of clinicians. DESIGN: Using Gibb's reflective cycle as a framework for journaling, this study employs reflexive and visual journaling through the lenses of a psychiatrist and an art therapist. Journal data were analysed using a thematic analysis approach. SETTING/PARTICIPANTS: The two first authors journaled 107 clinical encounters and created 36 pieces of response art detailing encounters with patients and their families, and clinical conversations in two palliative care centres. RESULTS: Patient attributes and the clinical environment were observed to influence psychological health in palliative care. The patient's ability to navigate dying, maintain personhood, exert resilience and experience satisfying relationships contribute to psychological health. A clinical environment comprising clinicians with holistic competencies, systems promoting interdisciplinary collaborations and a values-based culture that promotes patient centricity strengthens the delivery of psychological care. CONCLUSIONS: Good psychological health in palliative care extends beyond psychopathology and is influenced by the cardinal elements of being human, value systems and systemic elements in the therapeutic environment.

Prognostic analysis of rectal cancer patients after neoadjuvant chemoradiotherapy: different prognostic factors in patients with different TRGs.

PURPOSE: The extent of tumor regression varies widely among locally advanced rectal cancer (LARC) patients who receive neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME). The purpose of this retrospectively study is to assess prognostic factors in LARC patients with NCRT, and further to analyze survival outcomes in patients with different tumor regression grades (TRGs). METHODS: This study includes LARC patients who underwent NCRT and TME at our institution. We retrospectively analyzed the clinicopathological characteristics and survival of all patients, and performed subgroup analysis for patients with different TRGs. Survival differences were compared using the Kaplan-Meier method and the log rank test. Additionally, a multiple Cox proportional hazard model was used to identify independent prognostic factors. RESULTS: The study included 393 patients, with 21.1%, 26.5%, 45.5%, and 6.9% achieving TRG 0, TRG 1, TRG 2, and TRG 3, respectively. The overall survival (OS) rate and disease-free survival (DFS) rate for all patients were 89.4% and 70.7%, respectively. Patients who achieved TRG 0-3 had different 5-year OS rates (96.9%, 91.1%, 85.2%, and 68.8%, P = 0.001) and 5-year DFS rates (80.8%, 72.4%, 67.0%, 55.8%, P = 0.031), respectively. Multivariate analyses showed that the neoadjuvant rectal (NAR) score was an independent prognostic indicator for both overall survival (OS) (HR = 4.040, 95% CI = 1.792-9.111, P = 0.001) and disease-free survival (DFS) (HR = 1.971, 95% CI = 1.478-2.628, P ˂ 0.001). In the subgroup analyses, the NAR score was found to be associated with DFS in patients with TRG 1 and TRG 2. After conducting multivariate analysis, it was found that ypT stage was a significant predictor of DFS for TRG 1 patients (HR = 4.384, 95% CI = 1.721-11.168, P = 0.002). On the other hand, ypN stage was identified as the dominant prognostic indicator of DFS for TRG 2 patients (HR = 2.795, 95% CI = 1.535-5.091, P = 0.001). However, none of these characteristics was found to be correlated with survival in patients with TRG 0 or TRG 3. CONCLUSION: NAR score, in particular, appears to be the most powerful prognostic factor. It is important to consider various prognostic predictors for patients with different TRGs.

Optimization of traction parameters for lumbar scoliosis.

BACKGROUND: Scoliosis is a high incidence disease that endangers the physical and mental health of adolescents. Traction therapy, as a conservative treatment plan, is helpful to improve the recovery speed of patients by studying the influence of different traction factors on the therapeutic effect. METHODS: Based on the thin layer CT data of the lumbar spine of a 16-year-old patient with scoliosis, Mimics21.0 was used to extract the 3D digital model, and Geomagic Wrap2021 was used to perform the smooth surface. After that, SolidWorks was used to manually construct the structures, such as the intervertebral disc, and Ansys17.0 was used to add constraints, ligaments, and other features. Three-factor ANOVA was carried out after an orthogonal experiment that considered traction mode, traction angle, and traction force was finished. RESULTS: ① A three-dimensional biomechanical model of lumbar scoliosis was created. ② The model's correctness was confirmed by comparing it to the corpse and other finite element models, as well as by verifying it under a range of working settings. ③ Traction force (P = 0.000), traction angle (P = 0.000), the interaction between traction force and traction angle (P = 0.000), and the interaction between traction mode and traction angle (P = 0.045) were all significant. ④ The interaction between traction force and traction angle has the most significant effect on Cobb, and traction with a certain angle is better than traditional axial traction. ⑤ Traction mode is not significant, but the interaction between traction mode and traction angle is significant. CONCLUSIONS: A certain angle of traction can aid in improving outcomes and the traction force can be suitably decreased in the clinical formulation of the traction plan. The uniformity of correcting effect is more favorable when higher fixation techniques like positive suspension or traction bed traction are used, as opposed to overhanging traction.

The small-molecule drug homoharringtonine targets HSF1 to suppress pancreatic cancer progression.

Heat shock factor 1 (HSF1), an essential transcription factor for stress response, is exploited by various tumors to facilitate their initiation, progression, invasion, and migration. Amplification of HSF1 is widely regarded as an indicator in predicting cancer severity, the likelihood of treatment failure and reduced patient survival. Notably, HSF1 is markedly amplified in 40% of pancreatic cancer (PC), which typically have limited treatment options. HSF1 has been proven to be a promising therapeutic target for multiple cancers. However, a direct small molecule HSF1 inhibitor with sufficient bioactivity and reliable safety has not been developed clinically. In this study, we successfully established a high-throughput screening system utilizing luciferase reporter assay specifically designed for HSF1, which leads to the discovery of a potent small molecule inhibitor targeting HSF1. Homoharringtonine (HHT) selectively inhibited PC cell viability with high HSF1 expression and induced a markedly stronger tumor regression effect in the subcutaneous xenograft model than the comparator drug KRIBB11, known for its direct action on HSF1. Moreover, HHT shows promise in countering the resistance encountered with HSP90 inhibitors, which have been observed to increase heat shock response intensity in clinical trials. Mechanistically, HHT directly bound to HSF1, suppressing its expression and thereby inhibiting transcription of HSF1 target genes. In conclusion, our work presents a preclinical discovery and validation for HHT as a HSF1 inhibitor for PC treatment.

In vitro generation of trophoblast like stem cells from goat pluripotent stem cells.

Since the first mouse induced pluripotent stem cells (iPSCs) was derived, the in vitro culture of domestic iPSCs functionally and molecularly comparable with mouse iPSCs has been a challenge. Here, we established dairy goat iPSCs (giPSCs) from goat ear fibroblast cells with mouse iPSCs morphology, the expression of pluripotent markers and differentiation ability in vitro delivered by piggyBac transposon with nine Dox-inducible exogenous reprogramming factors. These reprogramming factors were bOMSK (bovine OCT4, CMYC, SOX2, and KLF4), pNhL (porcine NANOG and human LIN28), hRL (human RARG and LRH1), and SV40 Large T. Notably, AF-giPSCs (induced in activin A and bFGF condition) were capable of differentiation in embryoid bodies in vitro and could contribute to interspecies chimerism in mouse E6.5 embryos in vitro, demonstrating that AF-giPSCs have the developmental capability to generate some embryonic cell lineages. Moreover, Wnt/ß-catenin signaling has an important role in driving goat induced trophoblast-like stem cells (giTLSCs) from Dox-independent giPSCs. This study will support further establishment of the stable giPSC lines without any integration of exogenous genes.