Prognostic significance of pan-immune-inflammation value in hepatocellular carcinoma treated by curative radiofrequency ablation: potential role for individualized adjuvant systemic treatment.

BACKGROUND: This study aimed to explore the prognostic role of pan-immune-inflammation value (PIV) and develop a new risk model to guide individualized adjuvant systemic treatment following radiofrequency ablation (RFA) for early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Patients with early-stage HCC treated by RFA were randomly divided into training cohort A (n = 65) and testing cohort B (n = 68). Another 265 counterparts were enrolled into external validating cohort C. Various immune-inflammatory biomarkers (IIBs) were screened in cohort A. Prognostic role of PIV was evaluated and validated in cohort B and C, respectively. A nomogram risk model was built in cohort C and validated in pooled cohort D. Clinical benefits of adjuvant anti-angiogenesis therapy plus immune checkpoint inhibitor (AA-ICI) following RFA was assessed in low- and high-risk groups. RESULTS: The cutoff point of PIV was 120. High PIV was an independent predictor of unfavorable recurrence-free survival (RFS) and overall survival (OS). RFS and OS rates of patients with high PIV were significantly lower than those with low PIV both in cohort B (PRFS=0.016, POS=0.011) and C (PRFS<0.001, POS<0.001). The nomogram model based on PIV, tumor number and BCLC staging performed well in risk stratification in external validating cohort C. Adjuvant AA-ICI treatment showed an added benefit in OS (p = 0.011) for high-risk patients. CONCLUSIONS: PIV is a feasible independent prognostic factor for RFS and OS in early-stage HCC patients who received curative RFA. The proposed PIV-based nomogram risk model could help clinicians identify high-risk patients and tailor adjuvant systemic treatment and disease follow-up scheme.

Key findingsHigh pan-immune-inflammation value (PIV) is an independent indicator of unfavorable recurrence-free survival (RFS) and overall survival (OS) for early-stage hepatocellular carcinoma (HCC) patients who received curative radiofrequency ablation (RFA).Adjuvant anti-angiogenesis target therapy plus immune checkpoint inhibitor (AA-ICI) treatment showed added benefit in OS for the high-risk patients defined by a nomogram risk model based on PIV, tumor number and BCLC staging.What is known and what is new?Inflammation and impaired host immunity are associated with carcinogenesis and progression of HCC. Increasing evidences showed that immune-inflammatory biomarkers (IIBs) had prognostic roles in early-stage HCC patients who received RFA. However, prognostic potential of PIV has not been determined in this setting.Herein, high PIV was first reported to be an independent risk factor of poor RFS and OS in early-stage HCC patients treated by curative RFA and helped to discriminate patients between low- and high-risk groups. Adjuvant AA-ICI treatment following RFA was beneficial to OS of patients in the high-risk group.What is the implication, and what should change now?For early-stage HCC with high-risk factors (high PIV, multiple tumor foci and more advanced BCLC stage), intensive follow-up and adjuvant systemic therapy following curative RFA were warranted.

Hydrogel-based radio frequency H2S sensor for in situ periodontitis monitoring and antibacterial treatment.

Periodontitis, a chronic disease, can result in irreversible tooth loss and diminished quality of life, highlighting the significance of timely periodontitis monitoring and treatment. Meanwhile, hydrogen sulfide (H2S) in saliva, produced by pathogenic bacteria of periodontitis, is an important marker for periodontitis monitoring. However, the easy volatility and chemical instability of the molecule pose challenges to oral H2S sensing. Here, we report a wearable hydrogel-based radio frequency (RF) sensor capable of in situ H2S detection and antibacterial treatment. The RF sensor comprises an agarose hydrogel containing conjugated silver nanoparticles-chlorhexidine (AG-AgNPs-CHL hydrogel) integrated with split-ring resonators. Adhered to a tooth, the hydrogel-based RF sensor enables wireless transmission of sensing signals to a mobile terminal and a concurrent release of the broad-spectrum antibacterial agent chlorhexidine without complex circuits. With the selective binding of the AgNPs to the sulfidion, the RF sensor demonstrates good sensitivity, a wide detection range (2-30 µM), and a low limit of detection (1.2 µM). Compared with standard H2S measurement, the wireless H2S sensor can distinguish periodontitis patients from healthy individuals in saliva sample tests. The hydrogel-based wearable sensor will benefit patients with periodontitis by detecting disease-related biomarkers for practical oral health management.

A risk predictive model for determining the severity of coronary artery lesions in older postmenopausal women with coronary heart disease.

OBJECTIVE: To determine the risk factors affecting the severity of coronary artery disease (CAD) in older postmenopausal women with coronary heart disease (CHD) and to construct a personalized risk predictive model. METHODS: In this cohort study, clinical records of 527 female patients aged ≥60 with CHD who were hospitalized in the First Affiliated Hospital of the University of Science and Technology of China from March 2018 to February 2019 were analyzed retrospectively. The severity of CAD was determined using the Gensini scores that are based on coronary angiography findings. Patients with Gensini scores ≥40 and <40 were divided into high-risk (n=277) and non-high-risk groups (n=250), respectively. Logistic regression analysis was used to assess independent predictors of CAD severity. The nomogram prediction model of CAD severity was plotted by the R software. The area under the receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive efficiency of the nomogram model, and the decision curve analysis (DCA) was used to assess the clinical applicability of the nomogram model. RESULTS: Multivariate analysis showed that high-sensitivity C-reactive protein, RBC count, WBC count, BMI, and diabetes mellitus were independent risk factors associated with CAD severity in older menopausal women (P<0.05); the area under the ROC curve of the nomogram constructed based on the independent risk factors was 0.846 (95% CI: 0.756-0.937). The area under the ROC curve after internal validation of the nomogram by the Bootstrap method after resampling 1000 times was 0.840 (95% CI: 0.741-0.923). The calibration curve suggested that the nomogram had an excellent predictive agreement, and the DCA curve indicated that the net benefit of applying the nomogram was significantly higher than that of the "no intervention" and "all intervention" methods when the risk probability of patients with high-risk CAD severity was 0.30-0.81. CONCLUSION: A personalized risk assessment model was constructed based on the risk factors of severe CAD in older menopausal women with CHD, which had good prediction efficiency based on discrimination, calibration, and clinical applicability evaluation indicators. This model could assist cardiology medical staff in screening older menopausal women with CHD who are at a high risk of severe CAD to implement targeted interventions.

Association between emphysema and other pulmonary computed tomography patterns in primary varicella pneumonia: A retrospective cohort study.

This study aims to evaluate chest computed tomography (CT) findings in hospital patients with primary varicella pneumonia (PVP). We retrospectively analyzed CT images of 77 PVP patients using 3D Slicer, an open-source software, to model lesions and lungs. This retrospective cohort study was approved by the Institutional Review Board (Ethical Committee, Renmin Hospital, Hubei University of Medicine, Shiyan, China) and waived the requirement for written informed consent. The left lung was more frequently and severely affected in PVP, with significant differences between the 2 groups in CT involvement percentage of each lung region, except for total lung inflation. Group A showed higher median percentages of lung collapse compared to Group B. The extent of left lung involvement is a critical predictor of emphysema in PVP patients, highlighting the importance of also monitoring the right lung for more severe cases. Lower emphysema levels correspond to more collapsed and infiltrated lung segments, suggesting a more severe clinical presentation.

Hydraulic vulnerability difference between branches and roots increases with environmental aridity.

The vulnerability of plant xylem to embolism can be described as the water potential at which xylem conductivity is lost by 50% (P50). According to the traditional hypothesis of hydraulic vulnerability segmentation, the difference in vulnerability to embolism between branches and roots is positive (P50 root-branch > 0). It is not clear whether this occurs broadly across species or how segmentation might vary across aridity gradients. We compiled hydraulic and anatomical datasets from branches and roots across 104 woody species (including new measurements from 10 species) in four biomes to investigate the relationships between P50 root-branch and environmental factors associated with aridity. We found a positive P50 root-branch relationship across species, and evidence that P50 root-branch increases with aridity. Branch xylem hydraulic conductivity transitioned from more efficient (e.g., wider conduit, higher hydraulic conductivity) to safer (e.g., narrower conduit, more negative P50) in response to the increase of aridity, while root xylem hydraulic conductivity remained unchanged across aridity gradients. Our results demonstrate that the hydraulic vulnerability difference between branches and roots is more positive in species from arid regions, largely driven by modifications to branch traits.

Association between peripheral plasma cytokine levels and suicidal ideation in first-episode, drug-naïve major depressive disorder.

BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.

Electrical Transport and Dynamics of Confined DNA through Highly Conductive 2D Graphene Nanochannels.

Confining DNA in nanochannels is an important approach to studying its structure and transportation dynamics. Graphene nanochannels are particularly attractive for studying DNA confinement due to their atomic flatness, precise height control, and excellent mechanical strength. Here, using femtosecond laser etching and wetting transfer, we fabricate graphene nanochannels down to less than 4.3 nm in height, with the length-to-height ratios up to 103. These channels exhibit high stability, low noise, and self-cleaning ability during the long-term ionic current recording. We report a clear linear relationship between DNA length and the residence time in the channel and further utilize this relationship to differentiate DNA fragments based on their lengths, ranging widely from 200 bps to 48.5 kbps. The graphene nanochannel presented here provides a potential platform for label-free analyses and reveals fundamental insights into the conformational dynamics of DNA and proteins in confined space.

Epidemiological and genetic characteristics of norovirus in Hangzhou, China, in the postepidemic era.

OBJECTIVE: Norovirus (NoV) is an important human pathogen that can cause severe gastroenteritis in vulnerable populations. This study aimed to analyze the epidemiological and genetic characteristics of 2021-2023 NoV in Hangzhou, China. METHODS: This study enrolled patients aged 0-18 years who underwent NoV RNA detection in the hospital between January 2021 and October 2023 and analyzed the epidemiological characteristics of NoV. Polymerase chain reaction (PCR) was used to detect NoV RNA. Subtype classification and whole-genome sequencing were performed. RESULTS: There was a high prevalence of NoV infection in 2023, with NoV-positive samples accounting for 63.10 % of the total number of positive samples collected during the three-year period. The prevalence was abnormally high in summer, and the number of positive samples accounted for 48.20 % of the total positive samples for the whole year, which was much greater than the level in the same period in previous years (2023, 48.20% vs 2021, 13.66% vs 2022, 15.21 %). The GⅡ.4 subtype played a leading role, followed by increased mixed infection with GⅠ.5 and GⅡ.4. Whole-genome sequencing results suggested that GII.P16-GⅡ.4 had R297H and D372N key locus mutations. The evolutionary rate was 4.29 × 10-3 for the RdRp gene and 4.84 × 10-3 for the VP1 gene. The RdRp gene and VP1 gene of NoV GII.P16-GⅡ.4 have undergone rapid population evolution during the COVID-19 epidemic. CONCLUSION: In the summer of 2023, an abnormally high incidence of NoV appeared in Hangzhou, China. The major epidemic strain GII.P16-GⅡ.4 showed a certain range of gene mutations and a fast evolutionary rate.

Astrocyte activation in hindlimb somatosensory cortex contributes to electroacupuncture analgesia in acid-induced pain.

Background: Several studies have confirmed the direct relationship between extracellular acidification and the occurrence of pain. As an effective pain management approach, the mechanism of electroacupuncture (EA) treatment of acidification-induced pain is not fully understood. The purpose of this study was to assess the analgesic effect of EA in this type of pain and to explore the underlying mechanism(s). Methods: We used plantar injection of the acidified phosphate-buffered saline (PBS; pH 6.0) to trigger thermal hyperalgesia in male Sprague-Dawley (SD) rats aged 6-8 weeks. The value of thermal withdrawal latency (TWL) was quantified after applying EA stimulation to the ST36 acupoint and/or chemogenetic control of astrocytes in the hindlimb somatosensory cortex. Results: Both EA and chemogenetic astrocyte activation suppressed the acid-induced thermal hyperalgesia in the rat paw, whereas inhibition of astrocyte activation did not influence the hyperalgesia. At the same time, EA-induced analgesia was blocked by chemogenetic inhibition of astrocytes. Conclusion: The present results suggest that EA-activated astrocytes in the hindlimb somatosensory cortex exert an analgesic effect on acid-induced pain, although these astrocytes might only moderately regulate acid-induced pain in the absence of EA. Our results imply a novel mode of action of astrocytes involved in EA analgesia.

Scientific figures interpreted by ChatGPT: strengths in plot recognition and limits in color perception.

Emerging studies underscore the promising capabilities of large language model-based chatbots in conducting basic bioinformatics data analyses. The recent feature of accepting image inputs by ChatGPT, also known as GPT-4V(ision), motivated us to explore its efficacy in deciphering bioinformatics scientific figures. Our evaluation with examples in cancer research, including sequencing data analysis, multimodal network-based drug repositioning, and tumor clonal evolution, revealed that ChatGPT can proficiently explain different plot types and apply biological knowledge to enrich interpretations. However, it struggled to provide accurate interpretations when color perception and quantitative analysis of visual elements were involved. Furthermore, while the chatbot can draft figure legends and summarize findings from the figures, stringent proofreading is imperative to ensure the accuracy and reliability of the content.

Research on Visual Perception of Speed Bumps for Intelligent Connected Vehicles Based on Lightweight FPNet.

In the field of intelligent connected vehicles, the precise and real-time identification of speed bumps is critically important for the safety of autonomous driving. To address the issue that existing visual perception algorithms struggle to simultaneously maintain identification accuracy and real-time performance amidst image distortion and complex environmental conditions, this study proposes an enhanced lightweight neural network framework, YOLOv5-FPNet. This framework strengthens perception capabilities in two key phases: feature extraction and loss constraint. Firstly, FPNet, based on FasterNet and Dynamic Snake Convolution, is developed to adaptively extract structural features of distorted speed bumps with accuracy. Subsequently, the C3-SFC module is proposed to augment the adaptability of the neck and head components to distorted features. Furthermore, the SimAM attention mechanism is embedded within the backbone to enhance the ability of key feature extraction. Finally, an adaptive loss function, Inner-WiseIoU, based on a dynamic non-monotonic focusing mechanism, is designed to improve the generalization and fitting ability of bounding boxes. Experimental evaluations on a custom speed bumps dataset demonstrate the superior performance of FPNet, with significant improvements in key metrics such as the mAP, mAP50_95, and FPS by 38.76%, 143.15%, and 51.23%, respectively, compared to conventional lightweight neural networks. Ablation studies confirm the effectiveness of the proposed improvements. This research provides a fast and accurate speed bump detection solution for autonomous vehicles, offering theoretical insights for obstacle recognition in intelligent vehicle systems.

Comprehensive mapping of saliva by multiomics in children with idiopathic nephrotic syndrome.

AIM: Saliva can reflect an individual's physiological status or susceptibility to systemic disease. However, little attention has been given to salivary analysis in children with idiopathic nephrotic syndrome (INS). We aimed to perform a comprehensive analysis of saliva from INS children. METHODS: A total of 18 children (9 children with INS and 9 normal controls) were recruited. Saliva was collected from each INS patient in the acute and remission phases. 16S rRNA gene sequencing, widely targeted metabolomics, and 4D-DIA proteomics were performed. RESULTS: Actinobacteria and Firmicutes were significantly enriched in the pretreatment group compared with the normal control group, while Bacteroidota and Proteobacteria were significantly decreased. A total of 146 metabolites were identified as significantly different between INS children before treatment and normal controls, which covers 17 of 23 categories. KEGG enrichment analysis revealed three significantly enriched pathways, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and terpenoid backbone biosynthesis (P < 0.05). A total of 389 differentially expressed proteins were selected between INS children before treatment and normal controls. According to the KEGG and GO enrichment analyses of the KOGs, abnormal ribosome structure and function and humoral immune disorders were the most prominent differences between INS patients and normal controls in the proteomic analysis. CONCLUSION: Oral microbiota dysbiosis may modulate the metabolic profile of saliva in children with INS. It is hypothesized that children with INS might have "abnormal ribosome structure and function" and "humoral immune disorders".

Skin-Tarsus-Skin Combined with Orbicularis-Tarsus-Orbicularis Fixation Technique Creates a Double Eyelid: A Case Series.

Background: The skin-tarsus-skin and orbicularis-tarsus-orbicularis fixation methods are widely used in double-eyelid surgery. Both methods have limitations. In this study, the two surgical methods were integrated and applied to form a stable double eyelid that mimics the natural physiological structure with minimal visible scarring. Methods: At the inner, middle, and outer sites of the double-eyelid line, 7-0 silk sutures were passed successively through the orbicularis oculi muscle at the lower edge of the incision, the tarsus/anterior tarsus tissue, and the orbicularis oculi muscle at the upper edge of the incision, and the skin was sutured with 8-0 thread. The remaining parts were fixed with 8-0 silk sutures successively passed through the skin at the lower edge of the incision, tarsus/anterior tarsus tissue, and skin at the upper edge of the incision. Scar formation, incidence of complications, and patient satisfaction were observed and recorded during follow-up. Results: Fifty-eight patients were included. The follow-up ranged from 3 to 24 months (mean, 8 months) with 47 patients undergoing primary and 11 secondary/revision surgery. Twelve cases showed slight linear scars and in 46 cases, surgical marks were almost invisible, and there were no dynamic depressed scars. Evaluation of patient satisfaction showed high satisfaction scores (VAS score, 8.56 ±â€…0.51). The main reason for dissatisfaction was asymmetry of the double eyelid. There were no significant complications. Conclusion: A skin-tarsus-skin combined with orbicularis-tarsus-orbicularis fixation technique can produce a long-lasting, natural-looking double eyelid.

Family History of Type 2 Diabetes and Its Association with Beta Cell Function and Lipid Profile in Newly Diagnosed Pediatric Patients with Type 1 Diabetes.

OBJECTIVE: The objective of this study was to explore the associations between a family history of type 2 diabetes (T2D) and beta-cell function, as well as lipid profile, in pediatric patients newly diagnosed with type 1 diabetes (T1D). METHODS: A retrospective analysis was conducted on children under 14 years of age who were newly diagnosed with T1D at the Children's Hospital of Zhejiang University between August 2018 and August 2022. Clinical features, metabolic profiles, beta-cell function, and lipid profile were evaluated. RESULTS: A total of 316 children were diagnosed with new-onset T1D. Among them, 28.2% had a family history of T2D. Patients with T1D who had a family history of T2D experienced a later onset of the disease (p = 0.016), improved HOMA2-%B levels (p = 0.003), and increased concentrations of HDL-C (p = 0.005). In addition, no statistically significant differences in age at onset, HOMA2-%B levels, or HDL-C were found when assessing the interaction between family history of T2D and type of diabetes mellitus (autoimmune T1D/idiopathic T1D). CONCLUSION: A family history of T2D may contribute to the heterogeneity of T1D patients in terms of HOMA2-%B levels and lipid profile. This highlights the significance of taking into account T2D-related factors in the diagnosis and treatment of T1D.

Avenue to novel o-carboranyl boron compounds - reactivity study of o-carborane-fused aminoborirane towards organic azides.

Herein we report the reactivity study of o-carborane-fused bis(trimethylsilyl)aminoborirane towards three different types of organic azides, i.e., aryl, alkyl, and silyl azides. The reaction with ArN3 (Ar = 2,6-iPr2C6H4, 2,6-C6H3Cl2, 2,4,6-C6H2Br3, C6F5) resulted in the cycloaddition of ArN3 to the borirane BN unit accompanied by silyl migration. Conversely, in the reaction with BnN3, only the BnN3 : borirane 1 : 2 ring expansion product was obtained. Finally, the reaction with Me3SiN3 resulted in a formal nitrene insertion product under thermal conditions. All of the newly obtained o-carborane-fused BN-containing heterocycles were fully characterized, and the mechanism of these substituent-dependent reactions was studied using DFT calculations.

Human monkeypox virus: Epidemiologic review and research progress in diagnosis and treatment.

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.

Correlation of serum and local CXCL13 levels with disease severity in patients with non-traumatic osteonecrosis of femoral head.

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.

TP53 mitigates cisplatin resistance in non-small cell lung cancer by mediating the effects of resistant cell-derived exosome mir-424-5p.

Background: Cisplatin (DDP) is the principal agent used for chemotherapy in patients with non-small cell lung cancer (NSCLC). Nevertheless, DDP resistance is an essential cause for a worse prognosis of patient. Therefore, this study proposes to discover features of miR-424-5p in DDP resistance of NSCLC. Method: After exogenous modulation of miR-424-5p expression, A549 cell activity was measured using CCK-8 and flow cytometry. A549/DDP and A549/DDP-associated subcutaneous tumor model were constructed to investigate the effect of miR-424-5p on DDP resistance in NSCLC in vivo. TargetScan and JASPAR databases predicted the potential molecular mechanism of miR-424-5p. A549-and A549/DDP-derived exosomes were isolated and characterized using a transmission electron microscope and nanoparticle tracking analysis. Result: Overexpression of miR-424-5p facilitated proliferation and DDP resistance in A549 cells, and knockdown of miR-424-5p did the opposite. Knockdown of miR-424-5p enhanced DDP restriction on tumor weight and volume. Moreover, SOCS5 and SOCS56 (SOCS5/6) were downstream targets of miR-424-5p. miR-424-5p down-regulated SOCS5/6 expression to activate JAK2/STAT3 and PI3K/AKT pathways. Notably, tumor protein p53 (TP53) is a transcription factor for the miR-424-5p host gene, as confirmed by the dual-luciferase reporter gene. Cellular and animal experiments indicated that TP53 limited the regulatory function of miR-424-5p on NSCLC growth, DDP resistance, and related molecules. Interestingly, miR-424-5p was markedly enriched in A549/DDP cell-derived exosomes than in A549 cell-derived exosomes, and TP53 down-regulated miR-424-5p expression in A549/DDP cell-derived exosomes. Conclusion: DDP-resistant cell-derived exosome miR-424-5p contributes to NSCLC growth and DDP resistance by targeting SOCS5 and SOCS6 to activate JAK2/STAT3 and PI3K/AKT pathways, which are blocked by TP53.