Efficacy of different indocyanine green doses in fluorescent laparoscopic cholecystectomy: A prospective, randomized, double-blind trial.

BACKGROUND AND OBJECTIVES: Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC. METHODS: This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups. RESULTS: Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction. CONCLUSIONS: In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

Integration of multiomics analyses reveals unique insights into CD24-mediated immunosuppressive tumor microenvironment of breast cancer.

BACKGROUND: Tumor immunotherapy brings new light and vitality to breast cancer patients, but low response rate and limitations of therapeutic targets become major obstacles to its clinical application. Recent studies have shown that CD24 is involved in an important process of tumor immune regulation in breast cancer and is a promising target for immunotherapy. METHODS: In this study, singleR was used to annotate each cell subpopulation after t-distributed stochastic neighbor embedding (t-SNE) methods. Pseudo-time trace analysis and cell communication were analyzed by Monocle2 package and CellChat, respectively. A prognostic model based on CD24-related genes was constructed using several machine learning methods. Multiple quantitative immunofluorescence (MQIF) was used to evaluate the spatial relationship between CD24+PANCK+cells and exhausted CD8+T cells. RESULTS: Based on the scRNA-seq analysis, 1488 CD24-related differential genes were identified, and a risk model consisting of 15 prognostic characteristic genes was constructed by combining the bulk RNA-seq data. Patients were divided into high- and low-risk groups based on the median risk score. Immune landscape analysis showed that the low-risk group showed higher infiltration of immune-promoting cells and stronger immune reactivity. The results of cell communication demonstrated a strong interaction between CD24+epithelial cells and CD8+T cells. Subsequent MQIF demonstrated a strong interaction between CD24+PANCK+ and exhausted CD8+T cells with FOXP3+ in breast cancer. Additionally, CD24+PANCK+ and CD8+FOXP3+T cells were positively associated with lower survival rates. CONCLUSION: This study highlights the importance of CD24+breast cancer cells in clinical prognosis and immunosuppressive microenvironment, which may provide a new direction for improving patient outcomes.

HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription.

Lysine lactylation (Kla) links metabolism and gene regulation and plays a key role in multiple biological processes. However, the regulatory mechanism and functional consequence of Kla remain to be explored. Here, we report that HBO1 functions as a lysine lactyltransferase to regulate transcription. We show that HBO1 catalyzes the addition of Kla in vitro and intracellularly, and E508 is a key site for the lactyltransferase activity of HBO1. Quantitative proteomic analysis further reveals 95 endogenous Kla sites targeted by HBO1, with the majority located on histones. Using site-specific antibodies, we find that HBO1 may preferentially catalyze histone H3K9la and scaffold proteins including JADE1 and BRPF2 can promote the enzymatic activity for histone Kla. Notably, CUT&Tag assays demonstrate that HBO1 is required for histone H3K9la on transcription start sites (TSSs). Besides, the regulated Kla can promote key signaling pathways and tumorigenesis, which is further supported by evaluating the malignant behaviors of HBO1- knockout (KO) tumor cells, as well as the level of histone H3K9la in clinical tissues. Our study reveals HBO1 serves as a lactyltransferase to mediate a histone Kla-dependent gene transcription.

A colorimetric sensor based on 4-MPBA Au@AgNPs for accurately identification of EnshiYulu tea grade.

Enshi Yulu green tea (ESYL) is the most representative traditional steamed green tea in Enshi, Hubei. Different ESYL grades exhibit distinct flavors, tastes, and prices. In this study, a visual sensor based on 4-MPBA Au@AgNPs was developed for the rapid and accurate identification of ESYL grades. The recognition mechanism involved the binding of 4-MPBA Au@AgNPs with polyphenolic compounds in ESYL to form borate esters and the conversion of Ag+ to Ag0, with the generated Ag0 depositing on the surface of 4-MPBA Au@AgNPs. The results showed that the sensor can amplify the color differences of different grades of ESYL. The visual results were also validated by the partial least squares discriminant analysis model, demonstrating an enhancement in recognition accuracy from 68.2 % to 95.5 % compared to the original extraction solution. The colorimetric sensor developed in this study is expected to provide a new approach for traceability research of other foods.

A photo-responsive self-healing hydrogel loaded with immunoadjuvants and MoS2 nanosheets for combating post-resection breast cancer recurrence.

Tumor recurrence after surgical resection remains a significant challenge in breast cancer treatment. Immune checkpoint blockade therapy, as a promising alternative therapy, faces limitations in combating tumor recurrence due to the low immune response rate. In this study, we developed an implantable photo-responsive self-healing hydrogel loaded with MoS2 nanosheets and the immunoadjuvant R837 (PVA-MoS2-R837, PMR hydrogel) for in situ generation of tumor-associated antigens at the post-surgical site of the primary tumor, enabling sustained and effective activation of the immune response. This PMR hydrogel exhibited potential for near-infrared (NIR) light response, tissue adhesion, self-healing, and sustained adjuvant release. When implanted at the site after tumor resection, NIR irradiation triggered a photothermal effect, resulting in the ablation of residual cancer cells. The in situ-generated tumor-associated antigens promoted dendritic cell (DC) maturation. In a mouse model, PMR hydrogel-mediated photothermal therapy combined with immune checkpoint blockade effectively inhibited the recurrence of resected tumors, providing new insights for combating post-resection breast cancer recurrence.

Ultrasound-Base Radiomics for Discerning Lymph Node Metastasis in Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: Ultrasound is the imaging modality of choice for preoperative diagnosis of lymph node metastasis (LNM) in thyroid cancer (TC), yet its efficacy remains suboptimal. As radiomics gains traction in tumor diagnosis, its integration with ultrasound for LNM differentiation in TC has emerged, but its diagnostic merit is debated. This study assesses the accuracy of ultrasound-integrated radiomics in preoperatively diagnosing LNM in TC. METHODS: Literatures were searched in PubMed, Embase, Cochrane, and Web of Science until July 11, 2023. Quality of the studies was assessed by the radiomics quality score (RQS). A meta-analysis was executed using a bivariate mixed effects model, with a subgroup analysis based on modeling variables (clinical features, radiomics features, or their combination). RESULTS: Among 27 articles (16,410 TC patients, 6356 with LNM), the average RQS was 16.5 (SD:5.47). Sensitivity of the models based on clinical features, radiomics features, and radiomics features plus clinical features were 0.64, 0.76 and 0.69. Specificities were 0.77, 0.78 and 0.82. SROC values were 0.76, 0.84 and 0.81. CONCLUSION: Ultrasound-based radiomics effectively evaluates LNM in TC preoperatively. Adding clinical features does not notably enhance the model's performance. Some radiomics studies showed high bias, possibly due to the absence of standard application guidelines.

Reversible Dual Fluorescence-Lifetime Imaging of Mitochondrial GSH and Microviscosity: Real-Time Evaluation of Ferroptosis Status.

Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time (t1/2 = 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical Xc-/GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.

Construction of a gene model related to the prognosis of patients with gastric cancer receiving immunotherapy and exploration of COX7A1 gene function.

BACKGROUND: GC is a highly heterogeneous tumor with different responses to immunotherapy, and the positive response depends on the unique interaction between the tumor and the tumor microenvironment (TME). However, the currently available methods for prognostic prediction are not satisfactory. Therefore, this study aims to construct a novel model that integrates relevant gene sets to predict the clinical efficacy of immunotherapy and the prognosis of GC patients based on machine learning. METHODS: Seven GC datasets were collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database and literature sources. Based on the immunotherapy cohort, we first obtained a list of immunotherapy related genes through differential expression analysis. Then, Cox regression analysis was applied to divide these genes with prognostic significancy into protective and risky types. Then, the Single Sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to score the two categories of gene sets separately, and the scores differences between the two gene sets were used as the basis for constructing the prognostic model. Subsequently, Weighted Correlation Network Analysis (WGCNA) and Cytoscape were applied to further screen the gene sets of the constructed model, and finally COX7A1 was selected for the exploration and prediction of the relationship between the clinical efficacy of immunotherapy for GC. The correlation between COX7A1 and immune cell infiltration, drug sensitivity scoring, and immunohistochemical staining were performed to initially understand the potential role of COX7A1 in the development and progression of GC. Finally, the differential expression of COX7A1 was verified in those GC patients receiving immunotherapy. RESULTS: First, 47 protective genes and 408 risky genes were obtained, and the ssGSEA algorithm was applied for model construction, showing good prognostic discrimination ability. In addition, the patients with high model scores showed higher TMB and MSI levels, and lower tumor heterogeneity scores. Then, it is found that the COX7A1 expressions in GC tissues were significantly lower than those in their corresponding paracancerous tissues. Meanwhile, the patients with high COX7A1 expression showed higher probability of cancer invasion, worse clinical efficacy of immunotherapy, worse overall survival (OS) and worse disease-free survival (DFS). CONCLUSIONS: The ssGSEA score we constructed can serve as a biomarker for GC patients and provide important guidance for individualized treatment. In addition, the COX7A1 gene can accurately distinguish the prognosis of GC patients and predict the clinical efficacy of immunotherapy for GC patients.

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications.

Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in-depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.

Development of machine learning-based malignant pericardial effusion-related model in breast cancer: Implications for clinical significance, tumor immune and drug-therapy.

Background: Malignant pericardial effusion (MPE) is a common complication of advanced breast cancer (BRCA) and plays an important role in BRCA. This study is aims to construct a prognostic model based on MPE-related genes for predicting the prognosis of breast cancer. Methods: The BRCA samples are analyzed based on the expression of MPE-related genes by using an unsupervised cluster analysis method. This study processes the data by least absolute shrinkage and selection operator and multivariate Cox analysis, and uses machine learning algorithms to construct BRCA prognostic model and develop web tool. Results: BRCA patients are classified into three clusters and a BRCA prognostic model is constructed containing 9 MPE-related genes. There are significant differences in signature pathways, immune infiltration, immunotherapy response and drug sensitivity testing between the high and low-risk groups. Of note, a web-based tool (http://wys.helyly.top/cox.html) is developed to predict overall survival as well as drug-therapy response of BRCA patients quickly and conveniently, which can provide a basis for clinicians to formulate individualized treatment plans. Conclusion: The MPE-related prognostic model developed in this study can be used as an effective tool for predicting the prognosis of BRCA and provides new insights for the diagnosis and treatment of BRCA patients.

High Intensity Focused Ultrasound-Driven Nanomotor for Effective Ferroptosis-Immunotherapy of TNBC.

The heterogeneity of triple-negative breast cancers (TNBC) remains challenging for various treatments. Ferroptosis, a recently identified form of cell death resulting from the unrestrained peroxidation of phospholipids, represents a potential vulnerability in TNBC. In this study, a high intensity focused ultrasound (HIFU)-driven nanomotor is developed for effective therapy of TNBC through induction of ferroptosis. Through bioinformatics analysis of typical ferroptosis-associated genes in the FUSCCTNBC dataset, gambogic acid is identified as a promising ferroptosis drug and loaded it into the nanomotor. It is found that the rapid motion of nanomotors propelled by HIFU significantly enhanced tumor accumulation and penetration. More importantly, HIFU not only actuated nanomotors to trigger effective ferroptosis of TNBC cells, but also drove nanomotors to activate ferroptosis-mediated antitumor immunity in primary and metastatic TNBC models, resulting in effective tumor regression and prevention of metastases. Overall, HIFU-driven nanomotors show great potential for ferroptosis-immunotherapy of TNBC.

Effective substances and molecular mechanisms guided by network pharmacology: An example study of Scrophulariae Radix treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries.

ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.

Ethyl cinnamate suppresses tumor growth through anti-angiogenesis by attenuating VEGFR2 signal pathway in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated. AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis. MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model. RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor. CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

Microbubble Biointerfacing by Regulation of the Platelet Membrane Surfactant Activity at the Gas-Liquid Interface for Acute Thrombosis Targeting.

Biointerfacing nanomaterials with cell membranes has been successful in the functionalization of nanoparticles or nanovesicles, but microbubble functionalization remains challenging due to the unique conformation of the lipid monolayer structure at the gas-liquid interface that provides insufficient surfactant activity. Here, we describe a strategy to rationally regulate the surfactant activity of platelet membrane vesicles by adjusting the ratio of proteins to lipids through fusion with synthetic phospholipids (i.e., liposomes). A "platesome" with the optimized protein-to-lipid ratio can be assembled at the gas-liquid interface in the same manner as pulmonary surfactants to stabilize a microsized gas bubble. Platesome microbubbles (PMBs) inherited 61.4 % of the platelet membrane vesicle proteins and maintained the active conformation of integrin αIIbß3 without the talin 1 for fibrin binding. We demonstrated that the PMBs had good stability, long circulation, and superior functionality both in vitro and in vivo. Moreover, by molecular ultrasound imaging, the PMBs provide up to 11.8 dB of ultrasound signal-to-noise ratio enhancement for discriminating between acute and chronic thrombi. This surface tension regulating strategy may provide a paradigm for biointerfacing microbubbles with cell membranes, offering a potential new approach for the construction of molecular ultrasound contrast agents for the diagnosis of different diseases.

Comamonas endophytica sp. nov., a novel indole acetic acid producing endophyte isolated from bamboo in China.

Two novel indole acetic acid-producing strains, 5MLIRT and D4N7, were isolated from Indosasa shibataeoides in Yongzhou, Hunan province, and Phyllostachys edulis in Hangzhou, Zhejiang province, respectively. Based on their 16S rRNA sequences, strains 5MLIRT and D4N7 were closely related to Comamonas antarcticus 16-35-5T (98.4 % sequence similarity), and the results of 92-core gene phylogenetic trees showed that strains 5MLIRT and D4N7 formed a phylogenetic lineage within the clade comprising Comamonas species. The complete genome size of strain 5MLIRT was 4.49 Mb including two plasmids, and the DNA G+C content was 66.5 mol%. The draft genome of strain D4N7 was 4.26 Mb with 66.7 mol% G+C content. The average nucleotide identity and digital DNA-DNA hybridization values among strain 5MLIRT and species in the genus Comamonas were all below the species delineation threshold. The colonies of strain 5MLIRT and D4N7 were circular with regular margins, convex, pale yellow and 1.0-2.0 mm in diameter when incubated at 30 °C for 3 days. Strains 5MLIRT and D4N7 grew optimally at 30 °C, pH 7.0 and 1.0 % NaCl. The respiratory isoprenoid quinone was ubiquinone-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Polyphasic analyses indicated that strains 5MLIRT and D4N7 could be distinguished from related validly named Comamonas species and represent a novel species of the genus Comamonas, for which the name Comamonas endophytica sp. nov. is proposed. The type strain is 5MLIRT (=ACCC 62069T=GDMCC 1.2958T=JCM 35331T).

Intra-ovarian inflammatory states and their associations with embryo quality in normal-BMI PCOS patients undergoing IVF treatment.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the main cause of anovulatory infertility in women of reproductive age, and low-grade chronic inflammation plays a key role in the occurrence and development of PCOS. However, obesity, as a likely confounding factor, can affect the inflammatory state of PCOS patients. OBJECTIVE: The aim of this study was to comprehensively investigate intra-ovarian inflammatory states and their impact on embryo quality in PCOS patients with a normal BMI undergoing IVF treatment. METHODS: DIA-mass spectrometry-based proteomics and bioinformatic analysis were combined to comprehensively profile the protein expression of granulosa cells (GCs) from 5 normal-BMI PCOS patients and 5 controls. Thirty-four cytokines were further systematically detected in follicular fluid (FF) from 32 age- and BMI-matched normal-BMI patients using Luminex liquid chip suspension technology. Next, the differentially expressed cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA) in 24 newly recruited subjects, and the relationship between these cytokines and embryo quality in PCOS patients was analysed. Finally, these cytokine levels were compared and evaluated in PCOS patients with different androgen levels. RESULTS: Proteomic analysis showed that the suppression of substance metabolism and steroid biosynthesis, more interestingly, resulted in an enhanced immune and inflammatory response in the GCs of normal-BMI PCOS patients and prompted the involvement of cytokines in this process. Luminex analysis further showed that FF macrophage inflammatory protein-1 beta (MIP-1ß) and stromal cell-derived factor-1 alpha (SDF-1α) levels were significantly increased in normal-BMI PCOS patients compared to controls (P = 0.005; P = 0.035, respectively), and the ELISA results were consistent with these findings. Besides, FF MIP-1ß showed an inverse correlation with the number of D3 good-quality embryos and the good-quality blastocyst rate in patients with PCOS (P = 0.006; P = 0.003, respectively), which remained significant after correction for multiple comparisons. Moreover, SDF-1α levels had no relationship with embryo development in PCOS patients. Additionally, SDF-1α levels were significantly lower in PCOS patients with high androgen levels than in controls (P = 0.031). CONCLUSIONS: Local ovarian inflammation was present in normal-BMI PCOS patients, affecting follicular development, and FF MIP-1ß may be a potential biomarker associated with embryo quality in normal-BMI PCOS patients.

Clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion and modified posterior lumbar interbody fusion in the treatment of lumbar degenerative disease.

BACKGROUND: To compare the early clinical efficacy of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and modified posterior lumbar interbody fusion (MPLIF) in the treatment of lumbar degenerative disease (LDD). METHODS: A total of 37 patients who underwent PE-PLIF and 58 patients who underwent MPLIF from March 2019 to January 2022 were retrospectively reviewed. The operation time, intraoperative blood loss, post-operative hospitalization time, and post-operative bedrest time were recorded. The visual analogue scale (VAS) scores of leg pain and low back pain, Japanese Orthopaedic Association (JOA) scores, and the Oswestry Disability Index (ODI) scores were evaluated and compared before the operation, 3 days after the operation, 1 week after the operation, 1 month after the operation, 6 months after the operation and at the last follow-up. The modified MacNab's criteria were applied at the last follow-up. The fusion rate and surgical-related complications during follow-up were recorded. RESULTS: The average operation time in the PE-PLIF group was highly significant longer than that in the MPLIF group (P < 0.01). The intraoperative blood loss, post-operative hospitalization time, and post-operative bedrest time were significantly less in the PE-PLIF group than those in the MPLIF group (P < 0.01). There were highly significant differences in VAS scores of leg pain, VAS scores of low back pain, JOA scores, ODI scores at the last follow-up compared with those before the operation in the two groups (P < 0.01). Three days after the operation and 1 week after the operation, the VAS scores for low back pain and ODI were highly significant less in the PE-PLIF group than that in the MPLIF group (P < 0.01). Three days after the operation, the JOA scores were highly significant higher in the PE-PLIF group than that in the MPLIF group (P < 0.01). All patients showed intervertebral fusion at 6 months after the operation. Two patients (5.4%) in the PE-PLIF group experienced complications. CONCLUSION: Both PE-PLIF and MPLIF surgery were clinically effective and safe for patients with single-segment LDD. PE-PLIF surgery is a promising technique that can be used as an alternative treatment for single-segment LDD.

Diagnostic performance of MRI for residual or recurrent hepatocellular carcinoma after locoregional treatment according to contrast agent type: a systematic review and meta­analysis.

PURPOSE: The ideal contrast agent for imaging patients with hepatocellular carcinoma (HCC) following locoregional therapies (LRT) remains uncertain. We conducted a meta-analysis to assess the diagnostic performance of magnetic resonance imaging with extracellular contrast agent (ECA-MRI) and hepatobiliary agent (EOB-MRI) in detecting residual or recurrence HCC following LRT. METHODS: Original studies comparing the diagnostic performance of ECA-MRI and EOB-MRI were systematically identified through comprehensive searches in PubMed, EMBASE, Cochrane Library and Web of Science databases. The pooled sensitivity and specificity of ECA-MRI and EOB-MRI were calculated using a bivariate-random-effects model. Subgroup-analyses were conducted to compare the diagnostic performance of ECA-MRI and EOB-MRI according to different variables. Meta-regression analysis was employed to explore potential sources of study heterogeneity. RESULTS: A total of 15 eligible studies encompassing 803 patients and 1018 lesions were included. Comparative analysis revealed no significant difference between ECA-MRI and EOB-MRI in the overall pooled sensitivity (87% vs. 79%) and specificity (92% vs. 96%) for the detection of residual or recurrent HCC after LRT (P = 0.41), with comparable areas under the HSROC of 0.95 and 0.92. Subgroup analyses indicated no significant diagnostic performance differences between ECA-MRI and EOB-MRI according to study design, type of LRT, most common etiology of liver disease, baseline lesion size, time of post-treated examination and MRI field strength (All P > 0.05). CONCLUSION: ECA-MRI exhibited overall comparable diagnostic performance to EOB-MRI in assessing residual or recurrent HCC after LRT.

Ultrasound-Stimulated "Exocytosis" by Cell-Like Microbubbles Enhances Antibacterial Species Penetration and Immune Activation Against Implant Infection.

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.