Injectable hydrogel with doxorubicin-loaded ZIF-8 nanoparticles for tumor postoperative treatments and wound repair.

The need for tumor postoperative treatments aimed at recurrence prevention and tissue regeneration have raised wide considerations in the context of the design and functionalization of implants. Herein, an injectable hydrogel system encapsulated with anti-tumor, anti-oxidant dual functional nanoparticles has been developed in order to prevent tumor relapse after surgery and promote wound repair. The utilization of biocompatible gelatin methacryloyl (GelMA) was geared towards localized therapeutic intervention. Zeolitic imidazolate framework-8@ceric oxide (ZIF-8@CeO2, ZC) nanoparticles (NPs) were purposefully devised for their proficiency as reactive oxygen species (ROS) scavengers. Furthermore, injectable GelMA hydrogels loaded with ZC NPs carrying doxorubicin (ZC-DOX@GEL) were tailored as multifunctional postoperative implants, ensuring the efficacious eradication of residual tumor cells and alleviation of oxidative stress. In vitro and in vivo experiments were conducted to substantiate the efficacy in cancer cell elimination and the prevention of tumor recurrence through the synergistic chemotherapy approach employed with ZC-DOX@GEL. The acceleration of tissue regeneration and in vitro ROS scavenging attributes of ZC@GEL were corroborated using rat models of wound healing. The results underscore the potential of the multifaceted hydrogels presented herein for their promising application in tumor postoperative treatments.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Risk stratification of LA-NPC during chemoradiotherapy based on clinical classification and TVRR.

PURPOSE: To investigate the correlation between tumor volume reduction rate (TVRR) and prognosis in patients with diverse clinical types of nasopharyngeal carcinoma (NPC) undergoing chemoradiotherapy, thereby aptly categorizing risks and directing the personalized treatment of NPC. MATERIALS AND METHODS: A total of 605 NPC patients with varying clinical types were enrolled in this study and subsequently segregated into six subgroups based on their clinical types and TVRR. To accentuate the efficacy of grouping, Groups 1-6 underwent clustered analysis of hazard atio (HR) values pertaining to progression-free survival (PFS), forming three risk clusters denoted as low, intermediate, and high. The log-rank test was employed to discern differences, and R 4.1.1 was utilized for cluster analysis. RESULTS: According to survival rates, we classified the first (G2 and G4), second (G1 and G6), and third (G3 and G5) risk clusters as low-, intermediate-, and high-risk, respectively. When comparing risk stratification with the 8th edition of the TNM staging system, our classification exhibited superior predictive prognostic performance. Subgroup analysis of treatments for each risk cluster revealed that the PFS in the neoadjuvant chemotherapy (NACT) + concurrent chemoradiotherapy (CCRT) group surpassed that of the CCRT group significantly (p < 0.05). CONCLUSION: The reliance on clinical types and TVRR facilitates risk stratification of NPC during chemoradiotherapy, providing a foundation for physicians to tailor therapeutic strategies. Moreover, the risk cluster delineated for NPC patients during the mid-term of chemoradiotherapy stands as an independent prognostic factor for progression-free survival (PFS), overall survival (OS), distantmetastasis-free survival (DMFS), and local recurrence-free (LRRFS) posttreatment. Additionally, individuals in the high-risk cluster are recommended to undergo adjuvant chemotherapy after CCRT.

Pure testicular choriocarcinoma, a rare and highly malignant subtype with challenging treatment: A case report and review of the literature.

Testicular choriocarcinoma (CC) is the rarest subtype of germ cell tumours (GCTs) of the testis, with a high malignant potential and early haematogenous metastasis. Radical surgical resection should be performed primarily for histological diagnosis, while chemotherapy remains the mainstay of therapy for advanced disease. In the present study, the case of a 65-year-old male patient diagnosed with metastatic testicular CC, who did not fully respond to chemotherapy is reported. This patient underwent surgical removal of the testicular tumour, chemotherapy with etoposide and cisplatin, and radiotherapy of the intracranial lesions. Although the serum human chorionic gonadotropin (HCG) levels of the patient and most of the metastases continued decreasing during chemotherapy, complete response was not achieved after six cycles of chemotherapy. The patient refused high-dose chemotherapy and autologous stem cell transplantation due to severe side effects, and eventually developed respiratory failure on maintenance therapy with oral etoposide. A literature review was then performed, aiming to summarize the characteristics and therapeutic principles of testicular CC. In addition, the emerging therapeutic agents that could be used in maintenance therapy for GCTs, particularly for testicular CC, were also discussed. The limited clinical trials of targeted treatments showed potential benefit for long survival of patients with selected GCTs with fewer side effects. In particular, immunotherapy showed unique potential for testicular CC in preclinical studies, offering new approaches of maintenance therapy for advanced disease. Further studies should shed light on the identification of prognostic factors that predict the response to immune-based therapy in GCTs.

Mendelian randomization analysis identified tumor necrosis factor as being associated with severe COVID-19.

Background: Observational studies have shown that anti-tumor necrosis factor (TNF) therapy may be beneficial for patients with coronavirus disease 2019 (COVID-19). Nevertheless, because of the methodological restrictions of traditional observational studies, it is a challenge to make causal inferences. This study involved a two-sample Mendelian randomization analysis to investigate the causal link between nine TNFs and COVID-19 severity using publicly released genome-wide association study summary statistics. Methods: Summary statistics for nine TNFs (21,758 cases) were obtained from a large-scale genome-wide association study. Correlation data between single-nucleotide polymorphisms and severe COVID-19 (18,152 cases vs. 1,145,546 controls) were collected from the COVID-19 host genetics initiative. The causal estimate was calculated by inverse variance-weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were conducted to assess the validity of the causal relationship. Results: Genetically predicted TNF receptor superfamily member 6 (FAS) positively correlated with the severity of COVID-19 (IVW, odds ratio = 1.10, 95% confidence interval = 1.01-1.19, p = 0.026), whereas TNF receptor superfamily member 5 (CD40) was protective against severe COVID-19 (IVW, odds ratio = 0.92, 95% confidence interval = 0.87-0.97, p = 0.002). Conclusion: Genetic evidence from this study supports that the increased expression of FAS is associated with the risk of severe COVID-19 and that CD40 may have a potential protective effect against COVID-19.

Chinese herbal injections plus Western Medicine on inflammatory factors for patients with acute exacerbation of chronic obstructive pulmonary disease: a systematic review and network meta-analysis.

Background: Chinese herbal injections (CHIs) are commonly prescribed in China as adjuvant therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, evidence supporting the effect of CHIs on inflammatory factors for patients with AECOPD is insufficient, posing a challenge for clinicians to choose the optimal CHIs for AECOPD. This network meta-analysis (NMA) aimed to compare the effectiveness of several CHIs combined with Western Medicine (WM) and WM alone on the inflammatory factors in AECOPD. Methods: Randomized controlled trials (RCTs) on different CHIs for treating AECOPD were thoroughly searched from several electronic databases up to August 2022. The quality assessment of the included RCTs was conducted according to the Cochrane risk of bias tool. Bayesian network meta-analyses were designed to assess the effectiveness of different CHIs. Systematic Review Registration CRD42022323996. Results: A total of 94 eligible RCTs involving 7,948 patients were enrolled in this study. The NMA results showed that using Xuebijing (XBJ), Reduning (RDN), Tanreqing (TRQ), and Xiyanping (XYP) injections combined with WM significantly improved treatment effects compared to using WM alone. XBJ + WM and TRQ + WM significantly changed the level of C-reactive protein (CRP), white blood cells, percentage of neutrophils, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). TRQ + WM showed the most significant effect in reducing the level of procalcitonin. XYP + WM and RDN + WM could reduce the level of white blood cells and the percentage of neutrophils. A total of 12 studies reported adverse reactions in detail, and 19 studies demonstrated no significant adverse reactions. Conclusions: This NMA showed that using CHIs combined with WM could significantly reduce the level of inflammatory factors in AECOPD. A combination of TRQ and WM may be a relatively prior adjuvant therapy option for AECOPD treatment considering its effects in reducing the levels of the anti-inflammatory mediators.

Depression Exacerbates Dextran Sulfate Sodium-Induced Colitis via IRF5-Mediated Macrophage Polarization.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and concurrent depression are predisposed to severer disease activity and a worse prognosis. Macrophage polarization toward the M1 phenotype may contribute to the exacerbation of IBD with comorbid depression. Moreover, interferon regulatory factor 5 (IRF5) is involved in the pathogenesis of IBD. The aim of this study was to explore the role of IRF5 in macrophage polarization in the impact of depression upon colitis. METHODS: Depressive-like behavior was induced by repeated forced swim stress. Colon length, disease activity index (DAI), colon morphology, histology, ultrastructure of epithelial barrier, lamina propria macrophage polarization, and expression of IRF5 were compared between DSS colitis rats with and without depressive-like behavior. IRF5 shRNA was constructed to affect the rat peritoneal macrophages polarization in vitro. After IRF5 shRNA lentivirus was introduced into colon by enema, the colitis severity, lamina propria macrophage polarization, and TNF-α, IL-1ß, and IL-10 of colon tissues were measured. RESULTS: The study found severer colonic inflammation in depressed versus non-depressed DSS-colitis rats. Depressed DSS-colitis rats exhibited smaller subepithelial macrophages size and reduced intracellular granule diversity compared with nondepressed DSS-colitis rats. Increased polarization toward the M1 phenotype, elevated expression of IRF5, and co-expression of IRF5 with CD86 were found in depressed versus nondepressed DSS-colitis rats. Lentivirus-mediated shRNA interference with IRF5 expression switched rat peritoneal macrophage polarization from the M1 to the M2 phenotype, downregulated TNF-α, IL-1ß expression to a greater extent in depressed versus nondepressed colitis rats. CONCLUSIONS: IRF5-mediated macrophage polarization may likely underlie the deterioration of DSS-induced colitis caused by depression.

[Correlation between Expression of CD47 Molecule in Patients with Newly Diagnosed Adult Acute Myeloid Leukemia and Clinical Prognosis].

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34+, CD38+, CD123+ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION: The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.

METTL3-induced DLGAP1-AS2 promotes non-small cell lung cancer tumorigenesis through m6A/c-Myc-dependent aerobic glycolysis.

The critical roles of N6-methyladenosine (m6A) modification have been demonstrated by more and more evidence. However, the cross talk of m6A and long noncoding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC) tumorigenesis is still unclear. Here, this work focused on the functions and molecular mechanism of m6A-modified lncRNA DLGAP1 antisense RNA 2 (DLGAP1-AS2) in NSCLC. Microarray analysis found that lncRNA DLGAP1-AS2 is upregulated in NSCLC cells. Clinical data showed that DLGAP1-AS2 high-expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 overexpression promoted the aerobic glycolysis and DLGAP1-AS2 knockdown suppressed the tumor growth of NSCLC cells. Mechanistically, m6A methyltransferase METTL3 enhanced the stability of DLGAP1-AS2 via m6A site binding. Moreover, DLGAP1-AS2 interacted with YTHDF1 to enhance the stability of c-Myc mRNA through DLGAP1-AS2/YTHDF1/m6A/c-Myc mRNA. In conclusion, our work indicates the functions of m6A-modified DLGAP1-AS2 in the NSCLC aerobic glycolysis, disclosing a potential m6A-dependent manner for NSCLC treatment.

Venlafaxine as an Adjuvant Therapy for Inflammatory Bowel Disease Patients With Anxious and Depressive Symptoms: A Randomized Controlled Trial.

Background and Aims: The effect of antidepressant therapy on Inflammatory Bowel Disease (IBD) remains controversial. This trial aimed to assess whether adding venlafaxine to standard therapy for IBD improved the quality of life (QoL), mental health, and disease activity of patients with IBD with anxious and depressive symptoms. Methods: A prospective, randomized, double-blind, and placebo-controlled clinical trial was conducted. Participants diagnosed with IBD with symptoms of anxiety or depression were randomly assigned to receive either venlafaxine 150 mg daily or equivalent placebo and followed for 6 months. Inflammatory Bowel Disease Questionnaire (IBDQ), Mayo score, Crohn's disease activity index (CDAI), Hospital Anxiety and Depression Scale (HADS), and blood examination were completed before the enrollment, during, and after the follow-up. Mixed linear models and univariate analyses were used to compare groups. Results: Forty-five patients with IBD were included, of whom 25 were randomized to receive venlafaxine. The mean age was 40.00 (SD = 13.12) years old and 25 (55.6%) were male. Venlafaxine showed a significant improvement on QoL (p < 0.001) and disease course (p = 0.035), a greater reduction in HADS (anxiety: p < 0.001, depression: p < 0.001), Mayo scores (p < 0.001), and CDAI (p = 0.006) after 6 months. Venlafaxine had no effect on IL-10 expression, endoscopic scores, relapse rate, and use rate of biologics and corticosteroids, but did reduce serum level of erythrocyte estimation rate (ESR; p = 0.003), C-reactive protein (CRP; p < 0.001) and tumor necrosis factor-α (TNF-α; p = 0.009). Conclusions: Venlafaxine has a significantly beneficial effect on QoL, IBD activity, and mental health in patients with IBD with comorbid anxious or depressive symptoms. (Chinese Clinical Trial Registry, ID: ChiCTR1900021496).

Upregulated NORAD is implicated in apoptosis, inflammation, and oxidative stress in ulcerative colitis through the nuclear factor-κappaB signaling.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon. It has been discovered that long non-coding RNA activated by DNA damage (NORAD) is upregulated in UC patient-derived serums, but its functional mechanism in UC has not been disclosed. METHODS: Relative levels of NORAD in colonic mucosal tissues and TNF-α-stimulated human normal colonic mucosal cells (FHCs) were detected. Functional experiments were executed to evaluate the effects of NORAD silencing on TNF-α-induced FHC proliferation, apoptosis, inflammation, and oxidative stress. The molecular mechanism related to NORAD was predicted by starBase and confirmed by dual-luciferase reporter and RIP assays. RESULTS: Our data exhibited higher levels of NORAD in UC patient-derived colonic mucosal tissues and TNF-α-stimulated FHCs. Functional experiments presented that NORAD inhibition impaired TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. NORAD acted as a miR-552-3p sponge, and miR-552-3p silencing weakened NORAD inhibition-mediated effects on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Myeloid differentiation primary response gene 88 (MYD88) was verified as a miR-552-3p target, and MYD88 overexpression whittled miR-552-3p mimic-mediated inhibition on TNF-α-induced FHC apoptosis, inflammation, and oxidative stress. Notably, TNF-α-induced NORAD regulated the nuclear factor-κappaB (NF-κB) signaling via the miR-552-3p/MYD88 axis. CONCLUSION: NORAD participates in TNF-α-induced FHC apoptosis, inflammation, and oxidative stress via the NF-κB signaling via the miR-552-3p/MYD88 axis, offering new insights into the pathogenesis of UC.

Symptoms of anxiety/depression is associated with more aggressive inflammatory bowel disease.

Studies have demonstrated that inflammatory bowel disease (IBD) patients are at an increased risk of developing anxiety and/or depression. IBD patients with depression/anxiety have higher rates of hospitalization and increased disease severity than those without. So far, there is a paucity of data concerning the impact of anxiety/depression on Chinese IBD patients. The aim of this study was to find out the prevalence of symptoms of anxiety/depression in Chinese IBD population and its impact on IBD-related features. This is a cross-sectional study from the southwest China IBD referral center. Eligible participants were divided into those with symptoms of anxiety/depression and those without based on the Hospital Anxiety and Depression Scale (HADS). Demographic data and disease duration, IBD-related surgery, tobacco use, extra-intestinal manifestations, disease activity scores, endoscopic evaluation, laboratory data and current medication use were compared between two groups. A total of 341 IBD patients [221 Crohn's disease (CD) and 120 ulcerative colitis (UC)] were included. The prevalence of symptoms of anxiety/depression in IBD was 33.1%. CD patients with symptoms of anxiety/depression tended to have higher scores of simple endoscopic scores for Crohn's disease (SES-CD) (p = 0.0005). UC patients with symptoms of anxiety/depression had a significantly higher Mayo score (p = 0.0017) and ulcerative colitis endoscopic index of severity (UCEIS) (p < 0.0001) than their non-anxiety/depression counterparts. CD-related surgery (p = 0.012) and Crohn's disease activity index (CDAI) (p < 0.0001) were identified as independent risk factors for symptoms of anxiety/depression in CD, while corticosteroid use (p = 0.036) as an independent risk factor for symptoms of anxiety/depression in UC. This study helps our understanding of the prevalence of symptoms of anxiety/depression in IBD patients and its impact on IBD course and reminds us to pay more attention on IBD management with anxiety/depression.

Cang-Ai Volatile Oil Ameliorates Depressive Behavior Induced by Chronic Stress Through IDO-Mediated Tryptophan Degradation Pathway.

Background: Cang-ai volatile oil (CAVO) is a Chinese herbal volatile oil. Previous studies report that CAVO exhibits of anti-depressant and anti-inflammatory effects, and modulates activity of monoamine neurotransmitter. The current study sought to explore whether CAVO exhibits anti-depressant effects of CAVO through inhibition of inflammatory response and regulation of indoleamine 2 and 3-dioxygenase (IDO) mediated tryptophan degradation pathway. Methods: The study established chronic unpredictable mild stress (CUMS) depression-like model using rats. Body weight and food intake of animals were determined, and open field test (OFT), forced swim test (FST), and sucrose preference test (SPT) were performed to explored the behavioral changes of animals. Expression levels of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-10 (IL-10), kynurenine (KYN), quinolinic acid (QUIN), tryptophan (Trp), kynurenic acid (KYNA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) in the prefrontal cortex of CUMS rats were determined by ELISA. Co-localization of the microglia markers, Iba1 and IL-6 was determined by immunofluorescence. Western blotting was performed to determine the protein expression level of IDO1. Results: The findings of the current study showed that CAVO increased the body weight and food intake of rats and alleviated depression-like behaviors as shown in OFT, FST, and SPT analysis. ELISA assay showed that CAVO decreased IL-6, IL-1ß, TNF-α, and IFN-γ levels and increased levels of IL-4 and IL-10 in the prefrontal cortex of CUMS rats. Analysis showed that CAVO significantly reduced KYN and QUIN levels and the ratio of KYN/Trp, whereas it increased the levels of Trp, KYNA, 5-HT, and 5-HIAA. Immunofluorescence analysis showed that CAVO reduced the number of positive cells with co-localization of microglia markers, Iba1 and IL-6. Western blot analysis showed that CAVO decreased the protein expression level of IDO1 in rats. Conclusion: The findings show that the anti-depressant effects of CAVO are mainly attributed to inhibition of the activation of microglia and downregulation of IDO expression, thus inhibiting the kynurenine pathway and reversing the effects exerted on the 5-HT system.

Clinical features and monocyte/macrophage subsets characterization in granulomatous vs non-granulomatous Crohn's disease.

Aims: Granuloma, mainly composed of macrophages, is a histological feature of Crohn's disease (CD). However, its significance in CD has not been investigated adequately. Our study aims to address this issue by comparing the clinical manifestations and monocyte/macrophage subtypes between granulomatous and non-granulomatous CD.Materials and methods: Demographics, symptoms, endoscopic manifestations, histopathological features, and Montreal classification of patients with and without granulomas were compared. Flow cytometry was used to determine the phagocytosis and subsets of monocytes. ELISA was used to measure the plasma levels of TNF-α, IL-6, IL-1ß, IL-10, CCL22, and TGF-ß1. Immunohistochemistry was performed to quantify the expression of CD68, CD163 and iNOS.Results: Of the222 CD patients enrolled, granulomas were detected in 90. Compared with non-granulomatous CD patients, those with granulomas had younger age, increased rates of diarrhea and perianal complications, along with higher endoscopic score. Intestinal stenosis and crypt abscess were more frequently observed in granulomatous CD patients. A defective phagocytosis of monocytes was observed in granulomatous CD patients. Meanwhile, higher percentages of intermediate and non-classic monocytes, with a lower percentage of classic monocyte were found in them. Besides, they had higher levels of TGF-ß1 and IL-10, a lower level of TNF-α, an increased ratio of CD163+/CD68+cells, and a decreased ratio of iNOS+/CD68+ cells.Conclusions: Granulomatous CD patients exhibited different manifestations compared with their non-granulomatous counterparts. More aggressive therapy may be needed in granulomatous CD patients. Furthermore, the heterogeneity of monocyte/macrophage subsets and altered plasma cytokine may underlie the difference between those two groups.

Crohn's Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production.

BACKGROUND: Crohn's disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. METHODS: Eligible CD patients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn's disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, -interleukin 6 [IL-6], IL-1ß) and M2 cytokines (transforming growth factor [TGF]-ß1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. RESULTS: Depressed CD patients (n = 91) presented higher HBI, -SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1ß were increased while -classical monocyte (CD14++CD16-) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1ß correlated with HADS-D scores. CONCLUSION: Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CD patients with depressive symptoms.

Clinical Significance of 4L Lymph Node Dissection in Left Lung Cancer.

PURPOSE: To investigate the prognostic impact of 4L lymph node (LN) dissection in left lung cancer and to analyze the relative risk factors for 4L LN metastasis. PATIENTS AND METHODS: We retrospectively collected data from 657 patients with primary left lung cancer who underwent surgical pulmonary resection from January 2005 to December 2009. One hundred thirty-nine patients underwent 4L LN dissection (4LD+ group); the other 518 patients did not receive 4L LN dissection (4LD- group). Propensity score weighting was applied to reduce the effects of observed confounding between the two groups. Study end points were disease-free survival (DFS) and overall survival (OS). RESULTS: The metastasis rate of station 4L was 20.9%, which was significantly higher than those of station 7 (14.0%; P = .048) and station 9 (9.8%; P < .001). Station 4L metastasis was associated with most other LN station metastases in univariate analysis, but only station 10 LN metastasis was an independent risk factor for 4L LN metastasis (odds ratio, 0.253; 95% CI, 0.109 to 0.588; P = .001) in multivariate logistic analysis. The 4LD+ group had a significantly better survival than the 4LD- group (5-year DFS, 54.8% v 42.7%; P = .0376; 5-year OS, 58.9% v 47.2%; P = .0200). After allowing potential confounders in multivariate survival analysis, dissection of 4L LN retained its independent favorable effect on DFS (hazard ratio, 1.502; 95% CI, 1.159 to 1.947; P = .002) and OS (hazard ratio, 1.585; 95% CI, 1.222 to 2.057; P = .001). Propensity score weighting further confirmed that the 4LD+ group had a more favorable DFS ( P = .0014) and OS ( P < .001) than the 4LD- group. CONCLUSION: Station 4L LN involvement is not rare in left lung cancer, and dissection of the 4L LN station seems to be associated with a more favorable prognosis as compared with those who did not undergo this dissection.

Metastatic lymph node ratio and Lauren classification are independent prognostic markers for survival rates of patients with gastric cancer.

The long-term prognosis for patients with gastric cancer (GC) following radical resection remains poor. It is important to identify prognostic markers to predict survival. In the present retrospective study, the association between the metastatic lymph node ratio (rN) and the Lauren classification on predicting overall survival (OS) was investigated. Furthermore, a subgroup analysis was performed on the Lauren classification, using rN score as an independent prognostic marker. In total, 261 pathologically confirmed patients with GC were retrospectively reviewed. Kaplan-Meier curves and Cox's proportional hazards modeling were applied to analyze the OS of patients, and were utilized in the subgroup analysis. Receiver operating characteristic (ROC) curves were used to compare the accuracy of prognosis between the rN score and lymph node staging (N stage). The χ2 test was used to analyze the association between the rN score and Lauren classification. Univariate survival and multivariate analysis demonstrated that the rN score and Lauren classification were significant prognostic markers for patients with GC. The ROC analysis confirmed that the rN score was more effective than N staging for OS prediction. Subgroup analysis indicated that rN was more accurate at predicting OS time in patients with diffuse type GC. The rN score and the Lauren classification were independent prognostic factors for the OS of patients with GC following radical resection, and the rN score was more accurate than the N stage for predicting the prognosis. Overall, the rN may be suitable as an independent predictor for OS in patients with diffuse type GC.

Effect of pre-emptive analgesia by continuous femoral nerve block on early postoperative cognitive function following total knee arthroplasty in elderly patients.

To the best of our knowledge, the effect of pre-emptively blocking pain transmission on acute postoperative cognitive dysfunction (POCD) has not yet been assessed. Therefore, the present study aimed to investigate the effect of pre-emptive analgesia via a continuous femoral nerve block (CFNB) on postoperative pain and early cognitive function following total knee arthroplasty (TKA) surgery in elderly patients. CFNB was performed prior to TKA surgery in the pre-emptive analgesia group (n=30) and following TKA surgery in the control group (n=30). POCD was defined as a two-point reduction in the postoperative score compared with the preoperative score in the mini-mental state examination. The visual analog scale (VAS) was used to evaluate the intensity of pain at rest and during exercise. The intraoperative dose of remifentanil in the pre-emptive analgesia group was significantly lower than in the control group (P<0.01). In the preemptive analgesia group, VAS scores at three days post-surgery were lower than those in the control group (P<0.01). The incidence of POCD on the third postoperative day was slightly lower in the pre-emptive analgesia group compared with the control group. In conclusion, the results demonstrate that pre-emptive analgesia by CFNB may promote the recovery of early cognitive function following TKA in elderly patients.

Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers: a meta-analysis.

SETTING: For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet-lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. OBJECTIVE: To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. DESIGN: We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. RESULTS: Both high NLR (P < 0.00001) and high PLR (P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS (P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, (P = 0.006) extensive lymph nodetastasis(N2-3) (P = 0.01), poor differentiation (P = 0.0002) and vascular invasion(P = 0.002).There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. CONCLUSIONS: We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes.