ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.

Objective To explore the predictive value of artificial intelligence (AI)-based lung nodule CT quantitative analysis for the invasion degree of lung adenocarcinoma spectrum lesions. Methods According to the invasion degree of lung adenocarcinoma spectrum lesions, patients with surgically and pathologically confirmed lung adenocarcinoma spectrum lesions from January to June 2023 in Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University were retrospectively collected and divided into a non-invasive group and an invasive group, including atypical adenomatous hyperplasia, adenocarcinoma in situ, and minimally invasive adenocarcinoma patients in the non-invasive group, and invasive adenocarcinoma patients in the invasive group. All enrolled patients underwent chest CT before surgery, and then the lung nodules were quantitatively analyzed using an AI-based computer-aided diagnosis system to compare the related quantitative parameters of lung nodules that have been surgically removed and pathologically confirmed as lung adenocarcinoma spectrum lesions between the two groups. The relationship between various CT quantitative features and the invasion degree of lung adenocarcinoma spectrum lesions was analyzed. Results A total of 149 patients (149 lesions) were included, including 42 males and 107 females, aged 29-81 (56.35±10.75) years. There were 72 patients in the non-invasive group and 77 patients in the invasive group. Statistical differences were observed between the two groups in long diameter, short diameter, volume, surface area, mass, maximum cross-sectional area, 3D long diameter, maximum CT value, minimum CT value, average CT value, entropy, kurtosis, skewness, malignancy probability and other indicators (P<0.05). Multivariate binary logistic regression analysis showed that long diameter [OR=1.687, 95%CI (1.364, 2.085), P<0.001], average CT value [OR=1.006, 95%CI (1.002, 1.009), P=0.002], and malignancy probability [OR=1.034, 95%CI (1.005, 1.063), P=0.020] were independent risk factors for the invasion degree of lung adenocarcinoma. The predictive model combining the above parameters demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.951, sensitivity of 0.818, and specificity of 0.972. Using a Nomogram to quantify the three independent risk factors, the cross-validation was performed to evaluate the stability of the model, and the average C-index of cross-validation was 0.950, with each fold C-index >0.75, indicating that the prediction performance of the model was stable, and the calibration curve and decision curve indicated good predictive performance. Conclusion The visualization prediction model constructed by AI-based quantitative analysis of lung nodules in CT demonstrates significant discriminative effectiveness in the assessment of invasiveness in lung adenocarcinoma spectrum lesions. This visualization prediction model can provide a quantitative decision-making basis for the preoperative identification of the degree of invasiveness in lung adenocarcinoma spectrum lesions.

Background and Objectives: The Fractional Flow Reserve and Intravascular UltrasoundGuided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis (FLAVOUR) trial demonstrated non-inferiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) compared with intravascular ultrasound (IVUS)-guided PCI. We sought to investigate the cost-effectiveness of FFR-guided PCI compared to IVUS-guided PCI in Korea. Methods: A 2-part cost-effectiveness model, composed of a short-term decision tree model and a long-term Markov model, was developed for patients who underwent PCI to treat intermediate stenosis (40% to 70% stenosis by visual estimation on coronary angiography).The lifetime healthcare costs and quality-adjusted life-years (QALYs) were estimated from the healthcare system perspective. Transition probabilities were mainly referred from the FLAVOUR trial, and healthcare costs were mainly obtained through analysis of Korean National Health Insurance claims data. Health utilities were mainly obtained from the Seattle Angina Questionnaire responses of FLAVOUR trial participants mapped to EQ-5D. Results: From the Korean healthcare system perspective, the base-case analysis showed that FFR-guided PCI was 2,451 U.S. dollar lower in lifetime healthcare costs and 0.178 higher in QALYs compared to IVUS-guided PCI. FFR-guided PCI remained more likely to be cost-effective over a wide range of willingness-to-pay thresholds in the probabilistic sensitivity analysis. Conclusions Based on the results from the FLAVOUR trial, FFR-guided PCI is projected to decrease lifetime healthcare costs and increase QALYs compared with IVUS-guided PCI in intermediate coronary lesion, and it is a dominant strategy in Korea.

Objective: To compare the effects of high intensity interval training (HIIT) exercise prescription based on machine vision and routine on HIIT the physical and mental health of female college students with simple obesity, so as to provide a basis for the development of weight loss intervention plans for this population. Methods: From August 2023 to February 2024, 115 female college students with simple obesity, selected from Lianyungang Vocational and Technical College and East China Normal University, were randomly divided into a control group ( n =57) and an observation group ( n =58) according to a random number table. The control group received routine HIIT, while the observation group received machine vision based on HIIT exercise prescription (including image acquisition module, image processing module, database management module, backend computer processing and feedback, intelligent evaluation module, which could be customized according to the subjects preferences, providing exercise prescription based on the selected training program and supervised its standardized completion of the training plan). Both were intervened for 12 weeks, 30 minutes each time, once every 2 days, and rest every Sunday. The t-test was used to compare body shape, glucose and lipid metabolism, cardiopulmonary function indicators, anxiety and depression states between two groups before and after intervention. Results: Before intervention, there were no statistically significant differences in physical and mental health status indicators between two groups of female college students ( t =0.13-0.86, all P >0.05). After intervention, body mass indexes, waist hip ratios, body fat percentage, fasting plasma glucose, 2hour postprandial plasma glucose, hemoglobin A1c, triglycerides, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), anxiety and depression scores were all reduced in both groups ( t-observation =-6.94 to -12.92, t-control =-2.71 to -10.95 ), of which the observation group [(23.46±2.18)kg/m 2, 0.70±0.06, (28.03±3.16)%, (4.55±0.67)mmol/L, (6.03±0.74)mmol/L, (5.10±0.70)%, (1.63±0.31)mmol/L, (4.24±0.58)mmol/L, (2.45±0.43)mmol/L, 35.28±4.76, and 33.03±4.03] were lower compared with the control group [(26.54±2.32)kg/m 2, 0.77±0.06, (30.74±4.38)%, (5.03±0.76)mmol/L, (6.62±0.82)mmol/L, (5.82±0.73)%, (1.98±0.35)mmol/L, (4.95±0.61)mmol/L, (2.88±0.47)mmol/L, 39.18±5.04, and 37.25±4.16] ( t =-7.34, -6.26 , -3.81, -3.59, -4.05, -5.40, -5.68, -6.40, -5.12, -4.27, -5.53)(all P <0.05). After intervention, high density lipoprotein cholesterol, stroke volume, left ventricular ejection fraction, maximum oxygen consumption, volume of tidal, and vital capacity increased in both groups ( t-observation =7.43-18.23, t-control =3.89-10.13), of which the observation group [(1.49±0.22)mmol/L, ( 72.35± 4.69)mL, (68.95±5.10)%, (36.97±3.22)mL/(kg ·( min), (25.29±4.11)mL/(kg · ( min), and (3 374.26±169.54)mL] were higher compared with the control group [(1.23±0.20)mmol/L, (67.32±4.06)mL, (64.83±5.05)%, (33.24±3.14)mL/(kg · ( min), (23.01± 3.58 )mL/(kg · ( min), and (3 197.50±125.81)mL] ( t =6.63, 6.15, 4.35, 6.29, 3.17, 6.34)(all P <0.05). Conclusion HIIT exercise prescription based on machine vision has better effects than routine HIIT on impoving the body shape, glucose and lipid metabolism, cardiopulmonary function of female college students with simple obesity, and also their mental health.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

INTRODUCTION: The primary objective of this guideline is to establish evidence-based recommendations for the clinical use of parenteral nutrition (PN) in adult patients within the acute hospital setting in Singapore. METHOD: An expert workgroup, consisting of healthcare practitioners actively involved in clinical nutrition support across all public health institutions, systematically evaluated existing evidence and addressed clinical questions relating to PN therapy. RESULTS: This clinical practice guideline developed 30 recommendations for PN therapy, which cover these key aspects related to PN use: indications, patient assess-ment, titration and formulation of PN bags, access routes and devices, and monitoring and management of PN-related complications. CONCLUSION This guideline provides recommendations to ensure appropriate and safe clinical practice of PN therapy in adult patients within the acute hospital setting.
Humans ; Singapore ; Parenteral Nutrition/adverse effects* ; Adult

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Noncoding RNAs (ncRNAs) are a class of RNA molecules with little or no protein-coding potential. Emerging evidence indicates that ncRNAs are frequently dysregulated and play pivotal roles in the pathogenesis of pancreatic cancer. Their aberrant expression can arise from chromosomal abnormalities, dysregulated transcriptional control, and epigenetic modifications. ncRNAs function as protein scaffolds or molecular decoys to modulate interactions between proteins and other biomolecules, thereby regulating gene expression and contributing to pancreatic cancer progression. In this review, we summarize the mechanisms underlying ncRNA dysregulation in pancreatic cancer, emphasize the biological significance of ncRNA-protein interactions, and highlight their clinical relevance. A deeper understanding of ncRNA-protein interactions is essential to elucidate molecular mechanisms and advance translational research in pancreatic cancer.
Humans ; Pancreatic Neoplasms/metabolism* ; RNA, Untranslated/metabolism* ; Gene Expression Regulation, Neoplastic/genetics*