Clinical performance of the ASAS health index in chinese patients with ankylosing spondylitis and its influencing factors.

OBJECTIVE: The aim of this study was to investigate the status of health-related quality of life in Chinese patients with ankylosing spondylitis (AS) and to analyze factors associated with the Assessment of SpondyloArthritis international Society Health Index (ASAS-HI) in AS and its relationship with disease activity and psychological status. METHODS: A cross-sectional study of 484 patients with AS attending 10 hospitals in China from March 2021 to September 2023 was recruited. The ASAS-HI assessed general health and functional status; the Depression Anxiety Stress Scales (DASS-21) assessed psychological disorders such as anxiety, depression, and stress; and the Functional Assessment of Chronic illness Therapy-Fatigue Scale (FACIT-F) assessed patients' fatigue symptoms; the Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Measurement Index (BASMI) were used to assess patients' disease activity and functional impairment. The correlation between ASAS-HI and the ASDAS, poor psychological status, and fatigue symptoms was observed. Univariate and multivariate logistic regression analyses were used to explore the relevant influencing factors of ASAS-HI. RESULTS: A total of 484 patients were included in this study of whom 162 were in poor health, 139 in moderate health, and 183 in good health. On univariate analysis, disease activity is an important factor affecting ASAS-HI. People with extremely high disease activity (ASDAS ≥ 3.5) had a 12 times elevated risk of having poor health status (OR = 12.53; P < 0.001). Other significant covariates included age ≥ 36 (OR = 1.58; P = 0.015), BMI ≥ 24 kg/m2 (OR = 2.93; P = 0.013), smoke (OR = 1.96; P = 0.002), BASFI (OR = 1.49; P < 0.001), BASMI (OR = 1.22; P < 0.001), fatigue (OR = 6.28; P < 0.001), and bad psychological conditions such as depression (OR = 10.86; P < 0.001), anxiety (OR = 3.88; P < 0.001), and stress (OR = 4.65; P < 0.001). The use of bMARDs is inversely associated with the appearance of adverse health status (OR = 0.54; P = 0.012). There was no significant relationship between HLA-B27 and sex. Multivariable logistic regression showed that higher disease activity (ASDAS ≥ 3.5) (OR = 5.14; P = 0.005), higher scores of BASMI (OR = 1.10; P = 0.009), self-reported depression (OR = 3.68; P = 0.007), and fatigue (OR = 2.76; P < 0.001) were factors associated with adverse health status. CONCLUSION: The health status of AS patients is related to age, BMI, smoking, disease activity, poor psychological status, and fatigue and is influenced by a combination of multiple factors such as emotional state, economic level, pain, and dysfunction. Therefore, clinicians should pay attention to the early assessment of ASAS-HI in order to improve the prognosis of the disease. Key Points •Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease with a long course and heavy disease burden, which greatly affects patients' quality of life. Therefore, this study aims to evaluate the health status of ankylosing spondylitis in the Chinese population and its influencing factors. •This is a multi-center cross-sectional study in China, which can better reflect the overall situation of the Chinese population.

Y-90 Radioembolization and PD-1 Inhibitor as Neoadjuvant Treatment in Hepatocellular Carcinoma.

This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.

Effect of Carbon Nanofiber Distribution on Mechanical Properties of Injection-Molded Aramid-Fiber-Reinforced Polypropylene.

The mechanical recycling of discarded plastic products as resources for environmental preservation has recently gained research attention. In this context, it is necessary to use waste materials for fiber-reinforced thermoplastics (FRTP). Glass and carbon fibers are often damaged by shear and compression during melt-forming processes. To achieve a sustainable society, it is necessary for thermal recycling to produce minimal to no residue and for mechanical recycling to maintain the length of fibers used in FRTP to preserve their performance as a reinforcing agent. Aramid fibers (AFs) do not shorten during the melt-molding process, and their composites have excellent impact strength. On the other hand, plastics reinforced with glass or carbon fibers are reported to have a superior strength and modulus of elasticity compared to aramid fibers. This study investigates the dispersion of a carbon nanofiber (CNF), a whisker, as the third component in aramid-fiber-reinforced polypropylene (PP/AF). The results and discussion sections demonstrate how the dispersion of CNF in PP/AF can enhance the mechanical properties of injection-molded products without compromising their impact resistance. The proposed composition will have excellent material recyclability and initial mechanical properties compared to glass-fiber-reinforced thermoplastics.

Ubiquilin-4 induces immune escape in gastric cancer by activating the notch signaling pathway.

PURPOSE: We aimed to investigate the role of ubiquilin-4 in predicting the immunotherapy response in gastric cancer. METHODS: Retrospective RNA-sequencing and immunohistochemical analysis were performed for patients with gastric cancer who received programmed death-1 blockade therapy after recurrence. Multiplex immunohistochemistry identified immune cell types in gastric cancer tissues. We used immunocompetent 615 mice and immunodeficient nude mice to perform tumorigenic experiments. RESULTS: Ubiquilin-4 expression was significantly higher in responders (p < 0.05, false discovery rate > 2.5) and showed slight superiority over programmed death ligand 1 in predicting programmed death-1 inhibitor therapy response (area under the curve: 87.08 vs. 72.50). Ubiquilin-4-high patients exhibited increased CD4+ and CD8+ T cells, T follicular helper cells, monocytes, and macrophages. Ubiquilin-4-overexpressed mouse forestomach carcinoma cells showed significantly enhanced growth in immunocompetent mice but not in immunodeficient mice. Upregulation or downregulation of ubiquilin-4 synergistically affected programmed death ligand 1 at the protein and messenger RNA levels. Functional enrichment analysis revealed significant enrichment of the Notch, JAK-STAT, and WNT signaling pathways in ubiquilin-4-high gastric cancers. Ubiquilin-4 promoted Numb degaration, activating the Notch signaling pathway and upregulating programmed death ligand 1. CONCLUSIONS: Ubiquilin-4 may contribute to immune escape in gastric cancer by upregulating programmed death ligand 1 expression in tumor cells through Notch signaling activation. Thus, ubiquilin-4 could serve as a predictive marker for programmed death ligand 1 inhibitor therapy response in gastric cancer.

Irisin inhibits CCK-8-induced TNF-α production via integrin αVß5-NF-κB signaling pathways in Nile tilapia (Oreochromis niloticus).

Irisin, a secreted myokine generated by fibronectin type III domain-containing protein 5, has recently shown the potential to alleviate inflammation. Cholecystokinin-octapeptide (CCK-8) is closely associated with the inflammatory factor TNF-α, a central cytokine in inflammatory reactions. However, the interactions between irisin and CCK-8 in regulating TNF-α production and the underlying mechanism have not yet been elucidated. In the present study, irisin treatment inhibited the basal and the CCK-8-induced TNF-α production in vivo. Additionally, neutralizing circulating irisin using an irisin antiserum significantly augmented the CCK-8-induced stimulation of TNF-α levels. Moreover, the incubation of head kidney cells with irisin or CCK-8 has opposite effects on TNF-α secretion. Notably, irisin treatment inhibited basal and CCK-8-stimulated TNF-α release and gene transcription in head kidney cells. Mechanistically, the inhibitory actions of irisin on basal and CCK-8-induced TNF-α production could be negated by co-administered with the selective integrin αVß5 inhibitor cilengitide. In addition, the inhibitory effect of irisin on basal and CCK-8-triggered TNF-α production could be abolished by the inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, irisin impeded CCK-8-induced phosphorylation and degradation of IκBα, simultaneously inhibiting NF-κB phosphorylation, preventing its translocation into the nucleus, and suppressing its DNA-binding activity induced by CCK-8. Collectively, these results suggest that the inhibitory effect of irisin on TNF-α production caused by CCK-8 is mediated via the integrin αVß5-NF-κB signaling pathways in tilapia.

Effect of acupuncture on regulating IL-17, TNF-ɑ and AQPs in Sjögren's syndrome.

AIM: The aim of the study was to observe the effect of acupuncture on regulating interleukin (IL)-17, tumor necrosis factor (TNF)-ɑ, and aquaporins (AQPs) in Sjögren's syndrome (SS) on patients and on non-obese diabetic (NOD) models. METHODS: Levels of anti-AQP 1, 5, 8, and 9 antibodies, IL-17, and TNF-ɑ in the serum of SS patients were compared prior and following 20 acupuncture treatment visits during 8 weeks. While in murine model, five groups were divided to receive interventions for 4 weeks, including control, model, acupuncture, isoflurane, and hydroxychloroquine. The submaxillofacial gland index, histology, immunohistochemistry of AQP1, 5, salivary flow, together with IL-17, and TNF-ɑ expression in peripheral blood were compared among the groups. RESULTS: Acupuncture reduced IL-17, TNF-ɑ, and immunoglobin A levels, and numeric analog scale of dryness in 14 patients with SS (p < 0.05). The salivary flow was increased, and the water intake decreased in NOD mice receiving acupuncture treatments. IL-17 and TNF-ɑ levels in peripheral serum were down-regulated (p < 0.05) and AQP1, 5 expression in the submandibular glands up-regulated in mice. CONCLUSION: The effect on relieving xerostomia with acupuncture may be achieved by up-regulating the expression of AQP1. AQP5, down-regulating levels of IL-17 and TNF-ɑ, and a decrease in inflammation of glands.

Imaging glymphatic response to glioblastoma.

BACKGROUND: The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma. Impairment of the glymphatic system has been linked to several neurological conditions. Glioblastoma, also known as Glioblastoma multiforme (GBM) is a highly aggressive form of malignant brain cancer within the glioma category. However, the impact of GBM on the functioning of the glymphatic system has not been investigated. Using dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) and advanced kinetic modeling, we examined the changes in the glymphatic system in rats with GBM. METHODS: Dynamic 3D contrast-enhanced T1-weighted imaging (T1WI) with intra-cisterna magna (ICM) infusion of paramagnetic Gd-DTPA contrast agent was used for MRI glymphatic measurements in both GBM-induced and control rats. Glymphatic flow in the whole brain and the olfactory bulb was analyzed using model-derived parameters of arrival time, infusion rate, clearance rate, and residual that describe the dynamics of CSF tracer over time. RESULTS: 3D dynamic T1WI data identified reduced glymphatic influx and clearance, indicating an impaired glymphatic system due to GBM. Kinetic modeling and quantitative analyses consistently indicated significantly reduced infusion rate, clearance rate, and increased residual of CSF tracer in GBM rats compared to control rats, suggesting restricted glymphatic flow in the brain with GBM. In addition, our results identified compromised perineural pathway along the optic nerves in GBM rats. CONCLUSIONS: Our study demonstrates the presence of GBM-impaired glymphatic response in the rat brain and impaired perineural pathway along the optic nerves. Reduced glymphatic waste clearance may lead to the accumulation of toxic waste solutes and pro-inflammatory signaling molecules which may affect the progression of the GBM.

Glymphatic transport is reduced in rats with spontaneous pituitary tumor.

Background and objective: Pituitary tumor in patients induces adverse alterations in the brain, accompanied by cognitive deficits. Dysfunction of glymphatic waste clearance results in accumulation of neurotoxic products within the brain, leading to cognitive impairment. However, the status of glymphatic function in the brain with pituitary tumor is unknown. Using magnetic resonance imaging (MRI) and an advanced mathematical modeling, we investigated the changes of glymphatic transport in the rats carrying spontaneous pituitary tumor. Methods: Rats (22-24 months, female, Wistar) with and without pituitary tumor (n = 7/per group) underwent the identical experimental protocol. MRI measurements, including T2-weighted imaging and dynamic 3D T1-weighted imaging with intracisternal administration of contrast agent, were performed on each animal. The contrast-induced enhancement in the circle of Willis and in the glymphatic influx nodes were observed on the dynamic images and verified with time-signal-curves (TSCs). Model-derived parameters of infusion rate and clearance rate that characterize the kinetics of glymphatic tracer transport were evaluated in multiple representative brain regions. Results: Our imaging data demonstrated a higher incidence of partially enhanced circle of Willis (86 vs. 14%; p < 0.033) and a lower incidence of enhancement in glymphatic influx nodes of pituitary (71 vs. 100%) and pineal (57 vs. 86%) recesses in the rats with pituitary tumor than in the rats with normal appearance of pituitary gland, indicating an intensification of impaired peri-vascular pathway and impeded glymphatic transport due to the presence of pituitary tumor. Consistently, our kinetic modeling and regional cerebral tissue quantification revealed significantly lower infusion and clearance rates in all examined regions in rats with spontaneous pituitary tumor than in non-tumor rats, representing a suppressed glymphatic transport in the brain with pituitary tumor. Conclusion: Our study demonstrates the compromised glymphatic transport in the rat brain with spontaneous pituitary tumor. The reduced efficiency in cerebral waste clearance increases the risk for neurodegeneration in the brain that may underlie the cognitive impairment commonly seen in patients with pituitary tumors.

Detection of Plasma Antibodies Against CD25-Derived Peptide Antigens in Bladder Cancer.

BACKGROUND: Altered anti-CD25 antibody levels in plasma have been observed in patients with various solid malignancies. The present study aimed to determine whether circulating anti-CD25 antibody levels were altered in bladder cancer (BC). METHODS: An enzyme-linked immunosorbent assay was developed in-house to detect plasma IgG antibodies against three CD25-derived linear peptide antigens in 132 patients with BC and 120 control subjects. RESULTS: The Mann-Whitney U-test indicated that the plasma levels of anti-CD25a (Z = -10.11, p < 0.001), anti-CD25b (Z = -12.79, p < 0.001), and anti-CD25c IgG (Z = -11.95, p < 0.001) were significantly lower in BC patients than in the control group. Further analysis indicated that the plasma levels of anti-CD25a IgG antibody were stage-dependent and associated with different postoperative histological grades (U = 977.5, p = 0.003). The receiver operating characteristic curve analysis showed that the area under the ROC curve (AUC) was 0.869 for anti-CD25a IgG (95%, 0.825 - 0.913), 0.967 for anti-CD25b IgG (95%, 0.945 - 0.988), and 0.936 for anti-CD25c IgG (95%, 0.905 - 0.967), with a sensitivity of 91.3% for the anti-CD25a IgG assay, 98.8% for the anti-CD25b IgG assay, and 96.7% for the anti-CD25c IgG assay, against a specificity of 95%. CONCLUSIONS: The present study suggests that circulating anti-CD25 IgG may have a potential predictive value for clinical staging and histological grading of BC.

A novel 7-chemokine-genes predictive signature for prognosis and therapeutic response in renal clear cell carcinoma.

Background: Renal clear cell carcinoma (ccRCC) is one of the most prevailing type of malignancies, which is affected by chemokines. Chemokines can form a local network to regulate the movement of immune cells and are essential for tumor proliferation and metastasis as well as for the interaction between tumor cells and mesenchymal cells. Establishing a chemokine genes signature to assess prognosis and therapy responsiveness in ccRCC is the goal of this effort. Methods: mRNA sequencing data and clinicopathological data on 526 individuals with ccRCC were gathered from the The Cancer Genome Atlas database for this investigation (263 training group samples and 263 validation group samples). Utilizing the LASSO algorithm in conjunction with univariate Cox analysis, the gene signature was constructed. The Gene Expression Omnibus (GEO) database provided the single cell RNA sequencing (scRNA-seq) data, and the R package "Seurat" was applied to analyze the scRNA-seq data. In addition, the enrichment scores of 28 immune cells in the tumor microenvironment (TME) were calculated using the "ssGSEA" algorithm. In order to develop possible medications for patients with high-risk ccRCC, the "pRRophetic" package is employed. Results: High-risk patients had lower overall survival in this model for predicting prognosis, which was supported by the validation cohort. In both cohorts, it served as an independent prognostic factor. Annotation of the predicted signature's biological function revealed that it was correlated with immune-related pathways, and the riskscore was positively correlated with immune cell infiltration and several immune checkpoints (ICs), including CD47, PDCD1, TIGIT, and LAG-3, while it was negatively correlated with TNFRSF14. The CXCL2, CXCL12, and CX3CL1 genes of this signature were shown to be significantly expressed in monocytes and cancer cells, according to scRNA-seq analysis. Furthermore, the high expression of CD47 in cancer cells suggested us that this could be a promising immune checkpoint. For patients who had high riskscore, we predicted 12 potential medications. Conclusion: Overall, our findings show that a putative 7-chemokine-gene signature might predict a patient's prognosis for ccRCC and reflect the disease's complicated immunological environment. Additionally, it offers suggestions on how to treat ccRCC using precision treatment and focused risk assessment.

LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Molecular characterization and immune functions of lipasin in Nile tilapia (Oreochromis niloticus): Involvement in the regulation of tumor necrosis factor-α secretion.

Lipasin, the product of the angiopoietin-like 8 (angptl8) gene, is known as a critical regulator of plasma lipid metabolism. However, its immune function in vertebrates is currently poorly understood. By 5'/3'-rapid amplification of cDNA ends (RACE), we established the structural identity of Nile tilapia (Oreochromis niloticus) angptl8. The transcripts of tilapia angptl8 were widely expressed in various tissues, with the highest levels in the liver. Following lipopolysaccharide in vivo challenges, time-dependent angptl8 gene expression was observed in the head kidney and liver. On the basis of the sequence obtained, we produced recombinant lipasin that inhibited lipoprotein lipase activity. Treatment of head kidney leukocytes with lipasin stimulated tumor necrosis factor-α (TNF-α) secretion and gene expression. In addition, lipasin-induced TNF-α secretion could be prevented by inhibiting the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, lipasin enhanced the phosphorylation and degradation of IκBα and promoted translocation of the p65 subunit of NF-κB to the nucleus. Collectively, the current findings suggested that lipasin was involved in the immune response of Nile tilapia and stimulated TNF-α secretion by activating the NF-κB pathway in tilapia head kidney leukocytes.

Endothelial TFEB signaling-mediated autophagic disturbance initiates microglial activation and cognitive dysfunction.

Cognitive impairment caused by systemic chemotherapy is a critical question that perplexes the effective implementation of clinical treatment, but related molecular events are poorly understood. Herein, we show that bortezomib exposure leads to microglia activation and cognitive impairment, this occurs along with decreased nuclear translocation of TFEB (transcription factor EB), which is linked to macroautophagy/autophagy disorder, STAT3 (signal transducer and activator of transcription 3) phosphorylation and IL23A (interleukin 23 subunit alpha) expression. Pharmacological enhancement of TFEB nuclear translocation by digoxin restores lysosomal function and reduces STAT3-dependent endothelial IL23A secretion. As a consequence, we found that brain endothelial-specific ablation of Il23a ameliorated both microglia activation and cognitive dysfunction. Thus, the endothelial TFEB-STAT3-IL23A axis in the brain represents a critical cellular event for initiating bortezomib-mediated aberrant microglial activation and synapse engulfment. Our results suggest the reversal of TFEB nuclear translocation may provide a novel therapeutic approach to prevent symptoms of cognitive dysfunction during clinical use of bortezomib.Abbreviations: AAV: adeno-associated virus; BBB: blood-brain barrier; BTZ: bortezomib; DG: digoxin; DGs: dentate gyrus; DLG4/PSD95: discs large MAGUK scaffold protein 4; HBMECs: human brain microvascular endothelial cells; HP: hippocampus; IL23A: interleukin 23 subunit alpha; MBVECs: mouse brain vascular endothelial cells; mPFC: medial prefrontal cortex; NORT: novel object recognition test; OLT: object location test; PLX5622: 6-fluoro-N-([5-fluoro-2-methoxypyridin-3-yl]methyl)-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3- yl)methyl; PPP3/calcineurin: protein phosphatase 3; SBEs: STAT3 binding elements; shRNA: small hairpin RNA; SLC17A7/VGLUT1: solute carrier family 17 member 7; SLC32A1/VGAT: solute carrier family 32 member 1; STAT3: signal transducer and activator of transcription 3, TFEB: transcription factor EB; Ub: ubiquitin.

A Chinese version of the revised Fibromyalgia Impact Questionnaire: A validation study.

OBJECTIVE: The revised Fibromyalgia Impact Questionnaire (FIQR) was developed to measure the quality of life of patients with fibromyalgia in randomized controlled trials and routine care. The purpose of this study was to translate and adapt the FIQR from English to Chinese, and to examine the validity and reliability of the Chinese version of the FIQR (CFIQR). METHODS: Following the translation of the FIQR, fibromyalgia patients from 6 centers were recruited and completed the CFIQR, the validated Chinese version of the Medical Outcome Study Short Form 36 Health Survey (SF-36) and the Beck Depression Inventory (BDI). In this study, Cronbach's alpha coefficient, test-retest reliability and item total correlation were used for evaluating external and internal reliability; and criterion and structural validity were evaluated. RESULTS: A total of 200 fibromyalgia patients completed the study. The internal consistency was excellent (Cronbach's alpha .90, .88, .88 and .93 for function, overall impact, symptoms scales and total score, respectively; item-total correlations from .25 to .83.) Test-retest reliability levels of the CFIQR total and subscale scores were strong correlation (intraclass correlation coefficient >0.75). Furthermore, there were significant correlations between the 3 subscale and the total score of the CFIQR and the SF-36, as well as the CFIQR and the BDI, by criterion validity (P < .01). Confirmatory factor analysis gave an acceptable value for structural validity according to the 3-factor structures of function, overall impact and symptoms. CONCLUSIONS: The CFIQR is a valid and reliable instrument for both clinical practice and research purposes with Chinese speakers globally. [ClinicalTrials.gov: NCT03381131].

Laparoscopic Posterior Radical Antegrade Modular Pancreatosplenectomy for Distal Pancreatic Carcinoma.

Distal pancreatic carcinoma is a highly malignant tumor with strong invasiveness, often growing to the edge of the pancreas and penetrating the pancreatic capsule to infiltrate surrounding tissues. In conventional distal pancreatosplenectomy (DPS), tumor cells are prone to spread along the direction of blood and lymphatic reflux due to surgical compression. Additionally, inflammation makes it challenging to achieve R0 resection, leading to a lower patient survival rate. To address these limitations, radical antegrade modular pancreatosplenectomy (RAMPS) was developed, emphasizing deeper excision, including the left anterior renal fascia, the left anterior renal adipose sac, and even the left adrenal gland, to improve the R0 resection rate. With the advancement of minimally invasive surgical techniques, laparoscopic RAMPS (L-RAMPS) is being considered technically safe and feasible in oncology. However, due to technical difficulties and a lack of supporting evidence for clinical application, only a few institutions are currently conducting L-RAMPS. In this context, this article presents detailed techniques for laparoscopic posterior radical antegrade modular pancreatosplenectomy (L-pRAMPS), offering promise for future clinical applications.

Identification of metabolism-related genes for predicting peritoneal metastasis in patients with gastric cancer.

OBJECTIVE: The reprogramming of metabolism is an important factor in the metastatic process of cancer. In our study, we intended to investigate the predictive value of metabolism-related genes (MRGs) in recurrent gastric cancer (GC) patients with peritoneal metastasis. METHODS: The sequencing data of mRNA of GC patients were obtained from Asian Cancer Research Group (ACRG) and the GEO databases (GSE53276). The differentially expressed MRGs (DE-MRGs) between a cell line without peritoneal metastasis (HSC60) and one with peritoneal metastasis (60As6) were analyzed with the Limma package. According to the LASSO regression, eight MRGs were identified as crucially related to peritoneal seeding recurrence in patients. Then, disease free survival related genes were screened using Cox regression, and a promising prognostic model was constructed based on 8 MRGs. We trained and verified it in two independent cohort. RESULTS: We confirmed 713 DE-MRGs and the enriched pathways. Pathway analysis found that the MRG-related pathways were related to tumor metabolism development. With the help of Kaplan-Meier analysis, we found that the group with higher risk scores had worse rates of peritoneal seeding recurrence than the group with lower scores in the cohorts. CONCLUSIONS: This study developed an eight-gene signature correlated with metabolism that could predict peritoneal seeding recurrence for GC patients. This signature could be a promising prognostic model, providing better strategy in treatment.

Tertiary lymphoid structure patterns predicted anti-PD1 therapeutic responses in gastric cancer.

Objective: Recent studies have highlighted the distinct value of tertiary lymphoid structure (TLS) for immunotherapeutic response prediction. However, it remains unclear whether TLS could play such roles in gastric cancer (GC). Methods: In this study, tumor tissue slices from 292 GC patients from Zhongshan Hospital were firstly reviewed to explore the correlation between TLS and clinical characteristics. Subsequently, we curated 38 reported genes that may function as triggers of TLS and performed consensus molecular subtyping in public RNA-seq datasets to determine TLS patterns in GC. Based on the differentially expressed genes acquired from two TLS patterns, we quantified TLS-related genes on the principal component analysis (PCA) algorithm to develop TLS score. A Zhongshan immunotherapy cohort including 13 patients who received programmed cell death 1 (PD1) blockade therapy was established to conduct RNA sequencing analysis and multiplex immunohistochemistry (mIHC) tests using formalin-fixed and paraffin-embedded (FFPE) tissues. The corresponding TLS score and immune cell counts were further compared based on therapeutic response variations. Results: Mature TLS was revealed as an independent prognostic factor in 292 GC patients. Patients with higher TLS score was characterized by prolonged survival time and superior response to immunotherapy. TLS score was correlated with immunotherapy-related characters, such as microsatellite instability (MSI) and tumor mutation burden (TMB). In addition, RNA-seq data analysis in the Zhongshan immunotherapy cohort indicated that a higher TLS score was correlated with a superior response to PD1 blockade therapy. mIHC tests also revealed that PD1+CD8+ T cell counts were significantly increased in the high-TLS score group. Conclusions: This study highlighted that TLS was significantly associated with immune landscape diversity and complexity. Quantitatively evaluating TLS patterns of individual tumor will strengthen our understanding of TME characteristics and promote more effective immunotherapy strategies.

A deep learning-based diagnostic pattern for ultrasound breast imaging: can it reduce unnecessary biopsy?

Background: Early studies have demonstrated the potential of deep learning in bringing revolutionary changes in medical analysis. However, it is unknown which deep learning based diagnostic pattern is more effective for differentiating malignant and benign breast lesions (BLs) and can assist radiologists to reduce unnecessary biopsies. Methods: A total of 506 malignant BLs and 557 benign BLs were enrolled in this study after excluding incomplete ultrasound images. 396 malignant BLs and 447 benign BLs were included in the training cohort while 110 malignant and 110 benign BLs were included in the validation cohort. All BLs in the training and validation cohort were biopsy-proven. The most common convolutional neural networks (VGG-16 and VGG-19) were applied to identify malignant and benign BLs using grey-scale ultrasound images. Two radiologists determined the malignant (suggestion for biopsy) and benign (suggestion for follow-up) BLs with a 2-step reading session. The first step was based on conventional ultrasound (US) images alone to make a biopsy or follow-up decision. The second step was to take deep learning results into account for the decision adjustment. If a deep learning result of a first-classified benign BL was above the cut-off value, then it was re-classified as malignant. Results: In terms of area under the curve (AUC), the VGG-19 model yielded the best diagnostic performance in both training [0.939, 95% confidence interval (CI): 0.924-0.954] and testing dataset (0.959, 95% CI: 0.937-0.982). With the aid of deep learning models, the AUC of radiologists improved from 0.805 (95% CI: 0.744-0.865) to 0.827 (95% CI: 0.771-0.875, VGG-16) and 0.914 (95% CI: 0.871-0.957, VGG-19). The unnecessary biopsies decreased from 10.0% (11/110) to 8.2% (9/110) (assisted by VGG-16) and 0.9% (1/110) (assisted by VGG-19). Conclusions: The application of deep learning patterns in breast US may improve the diagnostic performance of radiologists by offering a second opinion. And thus, the assist of deep learning algorithm can considerably reduce the unnecessary biopsy rate in the clinical management of breast lesions.

Leclercia adecarboxylata infective endocarditis in a man with mitral stenosis: A case report and review of the literature.

BACKGROUND: Infective endocarditis (IE) is a rare disease with a high mortality rate. Leclercia adecarboxylata (L. adecarboxylata) is a movable Gram-negative bacillus of enterobacteriaceae, and it can rarely be a pathogen which often affects immunodeficient patients. There are about three cases of immunocompetent patients with monomicrobial L. adecarboxylata infection. There are only three reported cases of IE caused by L. adecarboxylata in the world. The mitral valve is often affected in IE, and the prognosis for IE with mitral valve lesions is often poor. CASE SUMMARY: A 51-year-old man was found to have moderate to severe mitral stenosis on echocardiography. He came to our Cardiothoracic Surgery Department for surgical management. A diastolic murmur was heard on auscultation of the heart in the mitral region. On the second day of hospitalisation, he presented with slurred speech, reduced muscle strength in the left limb, and acute cerebral infarction on cranial computed tomography. Surgical treatment was decided to postpone. On the ninth day of admission, the patient developed a sudden high fever and shock and was transferred to the Cardiac Intensive Care Unit, where echocardiogram revealed an anterior mitral valve leaflet vegetation. After empirical anti-infective treatment with vancomycin (1g q12h), an emergency valve replacement was performed. Bacterial culture identified L. adecarboxylata. Anti-infective treatment with piperacillin-tazobactam (4.5g q8h) was added for 4 wk. Follow-up echocardiography showed normal bioprosthetic valve function after mitral valve replacement. CONCLUSION: We report the first case of L. adecarboxylata IE in China, and clinicians should pay attention to this pathogen.