M1 Group Research Articles

Do disease status and race affect the efficacy of zoledronic acid in patients with prostate cancer? A systematic review and meta-analysis of randomized control trials.

BackgroundZoledronic acid (ZA) does not improve the overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC); however, little is known about the efficacy of ZA in to hormone-sensitive prostate cancer (HSPC), metastatic hormone-sensitive prostate cancer (mHSPC), and non- metastatic castration-resistant prostate cancer (nmCRPC). Therefore, we assessed the efficacy of ZA in patients with prostate cancer (PCa) and different disease statuses.MethodsFifteen eligible randomized-control trials (RCTs) with ZA intervention, including 8280 participants with HSPC, mHSPC, nmCRPC, and mCRPC, were analyzed. The primary and secondary outcome were overall survival(OS), and skeletal-related events (SREs), and bone mineral density (BMD).ResultsThe participants included 8280 men (7856 non-Asian and 424 Asian). Seven trials yielded a pooled hazard ratio (HR) of 0.95 (0.88, 1.03; P = 0.19) for OS. Subgroup analysis revealed no significant improvement in OS in the HSPC, castration-resistant prostate cancer (CRPC), M0 and M1(bone metastasis) groups, with pooled HR (95%CI) of 0.96 (0.88,1.05), 0.78 (0.46,1.33), 0.95 (0.81,1.13), 0.85 (0.69,1.04) respectively. The Asian group exhibited improved in OS with an HR of 0.67 (0.48, 0.95; P = 0.02), whereas the non-Asian group showed no improvement in OS with an HR of 0.97 (0.90, 1.06; P = 0.52). Five trials yielded pooled odds ratio (OR) of 0.65 (0.45, 0.95; P = 0.02) for SREs. In the subgroup, SREs were significantly decreased in the M1 and Asian groups with ORs of 0.65 (0.45, 0.95; P = 0.02) and 0.42 (0.24, 0.71; P = 0.001), respectively. Six trials yielded a pooled mean difference (MD) of 8.08 (5.79, 10.37; P < 0.001) for BMD. In the HSPC we observed a stable improvement in increased BMD percentage with an MD (95%CI) of 6.65 (5.67, 7.62) (P = 0.001).ConclusionsZA intervention does not significantly improve OS in patients with prostate cancer (HSPC, CRPC, M0, M1) but probably improves OS in the Asian populations. M1 and Asian groups had exhibit a significant reduction in SREs regardless of the HSPC or CRPC status after ZA administration. Moreover, ZA treatment increases BMD percentage.

Estimation of Epidermal growth factor (EGF), HER2, CA15-3 and Acid phosphatase in Iraqi breast cancer women

Breast cancer is one of frequent cancer that affects millions of people worldwide. Delayed diagnosis of these cancers has raised mortality and morbidity. Cancer biomarkers have tremendously increased the efficacy of treatment and the effectiveness of detection. This study aimed to investigate some biomarkers, including EGF, HER2, CA15-3, and Acid phosphatase, associated with early breast cancer (BC) diagnosis in Iraqi women. Carried on 90 Samples, the patients attended the Center for Early Detection of Breast Tumor at an oncology teaching hospital in Medical City. The study was conducted between 15/February (2021) and 20/July (2021). The consultant medical personnel made the diagnosis based on a Triple Assessment Technique, including physical breast examination, ultrasonography, with or without mammography and fine needle aspiration cytology. Female patients were divided into three groups (Benign, malignant and control). Benign B(34 patients) was split into subgroups, including. Benign premenopausal group B1(17 patients) Benign post-menopausal group B2(17patients) and malignant M(34 patients), malignant premenopausal group M1(17 patients) and malignant post-menopausal group M2(17 patients), and control group C include (11) premenopausal stage C1and (11) post-menopausal group C2. The value of EGF in Malignant cancer M1 (179.80 ±19.07) and M2(130.59 ±18.59)shows a highly significant (P≤0&gt;05) increase in comparison with benign cancer and B2 and healthy control C1and C2 groups, respectively but B1 and B2 shows high significant (P≤0&gt;05)decrease in comparison with C1 and C2 respectively. The values of HER2 show in B2(1.377±0.10); M1(11.76±0.10), and M2(11.79±0.09) increased significantly(P≤0.05) in comparison with C1, C2, B1 respectively. The values of CA-15-3 in M1 and M2 increase significantly(P≤0.05) compared with C1, C2, B1, and B2. The values of acid phosphatase in pre-and post-menopausal males in M1 and M2 increased significantly (p&lt;0.05) compared with C1andC2. Keywords: Epidermal growth factor, breast cancer, Acid phosphatase, HER2, CA15-3

Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

Salidroside Regulates Mitochondrial Homeostasis After Polarization of RAW264.7 Macrophages.

Salidroside has anti-inflammatory and antiatherosclerotic effects, and mitochondrial homeostasis imbalance is closely related to cardiovascular disease. The aim of this study was to investigate the effect of salidroside on mitochondrial homeostasis after macrophage polarization and elucidate its possible mechanism against atherosclerosis. RAW264.7 cells were stimulated with 1 μg·mL -1 Lipopolysaccharide and 50 ng·mL -1 IFN-γ establish M1 polarization and were also pretreated with 400 μM salidroside. The relative expression of proinflammatory genes was detected by RT-PCR whereas that of mitochondrial homeostasis-related proteins and nuclear factor kappa-B (NF-κB) was detected by WB. Levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential, and mass were measured by chemifluorescence whereas that of NF-κB nuclear translocation was detected by immunofluorescence. Compared with the Mφ group, the M1 group demonstrated increased mRNA expression of interleukin-1β , inductible nitric oxide synthase (iNOS), and tumor necrosis factor-α ; increased protein expression of iNOS, NOD-like receptor protein 3, putative kinase 1 , and NF-κB p65 but decreased protein expression of MFN2, Tom20, and PGC-1α; decreased mitochondrial membrane potential and mass; and increased ROS levels and NF-κB p65 nuclear translocation. Salidroside intervention decreased mRNA expression of interleukin-1β and tumor necrosis factor-α compared with the M1 group but did not affect that of iNOS. Furthermore, salidroside intervention prevented the changes in protein expression, mitochondrial membrane potential and mass, ROS levels, and NF-κB p65 nuclear translocation observed in the M1 group. In summary, salidroside ultimately inhibits M1 macrophage polarization and maintains mitochondrial homeostasis after macrophage polarization by increasing mitochondrial membrane potential, decreasing ROS levels, inhibiting NF-κB activation, and in turn regulating the expression of proinflammatory factors and mitochondrial homeostasis-associated proteins.

Comparison of Phytoremediation Potential of Nerium indicum with Inorganic Modifier Calcium Carbonate and Organic Modifier Mushroom Residue to Lead-Zinc Tailings.

At present, the application of phytoremediation technology in the ecological remediation of heavy metal tailings is receiving more and more attention. In this study, the physiological and biochemical response and tolerance mechanism of woody plant Nerium indicum to Pb and Zn under different proportions of inorganic modifier calcium carbonate (C1: 5%, C2: 10%, C3: 15%) and organic modifier mushroom residue (M1: 10%, M2: 20%, M3: 30%) was compared. The results showed that the pH value has a trend of C group > M group > CK group and organic matter has a trend of M group > CK group > C group. Phosphatase activity and catalase activity has a trend of M group > C group > CK group, but catalase was more vulnerable to the calcium carbonate concentration. Both modifiers can promote the transformation of Pb, Zn, Cu, and Cd in tailings to more stable organic bound and residual states. However, the stabilization effect of mushroom residue is better, and its stability is Pb, Zn > Cd, Cu. Both modifiers can increase the biomass of Nerium indicum and the modification effect of mushroom residue is better than calcium carbonate. Pb/Zn content and accumulation in Nerium indicum organs showed root > stem > leaf in all groups. Compared with the CK group, the enrichment coefficient of Pb/Zn in C1 and M1 groups decreased, while the translocation factor of Pb/Zn in C1 and M1 groups increased. With the increase in modifier concentration, the enrichment coefficient increases about 1.75~52.94%, but the translocation factor decreases rapidly (20.01~64.46%). Clearly, both the calcium carbonate and mushroom residue amendment could promote the growth ability of Nerium indicum in lead–zinc tailings and strengthen the phytoremediation potential.

Effects of salinity treatment on muscle quality and off‐flavour compounds of grass carp ( Ctenopharyngodon idella ) and black carp ( Mylopharyngodon piceus )

To investigate the effects of short-term salinity treatment on muscle quality and earthy and musty off-flavour compounds of freshwater fish, adult grass carp (1.25 ± 0.25 kg) and black carp (1.50 ± 0.30 kg) were reared at water salinities of 0‰, 5‰ and 7.5‰for 48 h. Muscle nutrients, amino acid, and fatty acid contents, texture properties, and earthy and musty off-flavour compounds were then determined. The content of total amino acid (TAA), Lys, Arg and essential amino acid index (EAAI) in the muscle of C7.5 group were elevated significantly compared with that in the control group (p < 0.05). The content of delicious amino acids (DAA) and EAAI in the muscle of M7.5 group was significantly higher than M0 and M5 groups (p < 0.05). The fatty acid content of the muscle was affected by salinity. In grass carp, the saturated fatty acid (SFA) content level was decreased significantly in the C5 and C7.5 groups (p < 0.05), while the monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) content levels were increased significantly in the C5 and C7.5 groups (p < 0.05). The ratio of n3/n6 PUFA increased significantly in the C7.5 group (p < 0.05). The PUFA content and the n3/n6 PUFA ratio were increased significantly in the M7.5 group (p < 0.05). With increasing salinity, the relative content levels of volatile compounds causing earthy and musty off-flavour in muscle were decreased significantly in 5‰ and 7.5‰ salinity groups both grass carp and black carp (p < 0.05). The textural properties of muscle, such as hardness, springiness, gumminess and chewiness, were improved in the C7.5 and M5 groups. These results suggest that a short-term salinity treatment in freshwater fish prior to selling can effectively improve muscle quality and decrease the content of earthy and musty off-flavour compounds, with ideal salinities of 5‰ or 7.5‰ for grass carp and 7.5‰ for black carp.

Sensorimotor performance after high-definition transcranial direct current stimulation over the primary somatosensory or motor cortices in men versus women

The primary somatosensory (S1) cortex is a central structure in motor performance. However, transcranial direct current stimulation (tDCS) research aimed at improving motor performance usually targets the primary motor cortex (M1). Recently, sex was found to mediate tDCS response. Thus, we investigated whether tDCS with an anodal electrode placed over S1 improves motor performance and sensation perception in men versus women. Forty-five participants randomly received 15-min high-definition tDCS (HD-tDCS) at 1 mA to S1, M1, or sham stimulation. Reaching performance was tested before and immediately following stimulation. Two-point orientation discrimination (TPOD) of fingers and proprioception of a reaching movement were also tested. Although motor performance did not differ between groups, reaching reaction time improved in the M1 group men. Reaching movement time and endpoint error improved in women and men, respectively. Correct trials percentage for TPOD task was higher in the S1 compared to the M1 group in the posttest and improved only in the S1 group. Reaching movement time for the proprioception task improved, overall, and endpoint error did not change. Despite the reciprocal connections between S1 and M1, effects of active tDCS over S1 and M1 may specifically influence sensation perception and motor performance, respectively. Also, sex may mediate effects of HD-tDCS on motor performance.

Hydration, reinforcing mechanism, and macro performance of multi-layer graphene-modified cement composites

Multi-layer graphene (MLG) has excellent mechanical properties and a unique stacked structure. In this paper, sulphoaluminate cement replaced ordinary portland cement to prepare low-carbon ecological ultra-high-performance-concrete (UHPC); the effects of MLG on the hydration, microstructure, and mechanical properties of UHPC were investigated, revealing the hydration mechanism and reinforcing mechanism of MLG on UHPC. Results show that adding MLG can significantly enhance the macro performance of UHPC. When the MLG content is 0.08%, UHPC has better macro performance. Compared with the M0 group, the flexural strength and compressive strength of the M3 group increased by 31.6%, 35.3%, 43.3%, 50.9%, and 9.5%, 13.5%, 22.2%, 21.7% after curing for 1 d, 7 d, 28 d, and 56 d, respectively. We quantitatively characterized the content of hydration product changes in UHPC. Various characterization analyses showed that the adsorption effect and nucleation effect of MLG promoted the hydrolysis and ions exchange of Ca2+ and Al3+, which provided sites for the growth of hydration products and accelerated the hydration process of cement, forming more hydration products, including AFt (ettringite) and AH3 (gibbsite). AFt, AH3, and MLG are closely connected, filling the pores and reducing the porosity of the matrix, optimizing the pore structure, and the medium and large pores transformed into micro-nano pores. Revealing the multi-level reinforcing mechanism, namely hydration products (AFt, AH3) and MLG filling the pores; MLG prevented the extension of micro-cracks and changed micro-cracks development path through filling effect, deflection effect, pulling out, and bridging effect.

Differentiation and prognostic stratification of acute myeloid leukemia by serum-based spectroscopy coupling with metabolic fingerprints.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by complex molecular and cytogenetic abnormalities. New approaches to predict the prognosis of AML have increasingly attracted attention. There were 98 non-M3 AML cases and 48 healthy controls were enrolled in the current work. Clinically routine assays for cytogenetic and molecular genetic analyses were performed on the bone marrow samples of patients with AML. Meanwhile, metabolic profiling of these AML subjects was also performed on the serum samples by combining Ag nanoparticle-based surface-enhanced Raman spectroscopy (SERS) with proton nuclear magnetic resonance (NMR) spectroscopy. Although most of the routine biochemical test showed no significant differences between the M0-M2 and M5 groups, the metabolic profiles were significantly different either between AML subtypes or between prognostic risk subgroups. Specific SERS bands were screened to serve as potential markers for AML subtypes. The results demonstrated that the classification models for M0-M2 and M5 shared two bands (i.e., 1328 and 741 cm-1 ), all came from nucleic acid signals. Furthermore, Metabolic profiles provided various differential metabolites responsible for different AML subtypes, and we found altered pathways mainly included energy metabolism like glycolysis, pyruvate metabolism, and metabolisms of nucleic acid bases as well as specific amino acid metabolisms. It is concluded that integration of SERS and NMR provides the rational and could be reliable to reveal AML differentiation, and meanwhile lay the basis for experimental and clinical practice to monitor disease progression and prognostic evaluation.

Effect of M2-like macrophage/microglia-derived mitochondria transplantation in treatment of mouse spinal cord injury

To investigate the effect of M2-like macrophage/microglia-derived mitochondria transplantation in treatment of mouse spinal cord injury (SCI). BV2 cells were classified into M1 (LPS treatment), M2 (IL-4 treatment), and M0 (no treatment) groups. After receiving M1 and M2 polarization, BV2 cells received microscopic observation, immunofluorescence staining [Arginase-1 (Arg-1)] and flow cytometry [inducible nitric oxide synthase (iNOS), Arg-1] to determine the result of polarization. MitoSox Red and 2, 7-dichlorodi-hydrofluorescein diacetate (DCFH-DA) stainings were used to evaluate mitochondrial function difference. Mitochondria was isolated from M2-like BV2 cells through differential velocity centrifugation for following transplantation. Then Western blot was used to measure the expression levels of the relevant complexes (complexes Ⅱ, Ⅲ, Ⅳ, and Ⅴ) in the oxidative phosphorylation (OXPHOS), and compared with M2-like BV2 cells to evaluate whether the mitochondria were obtained. Thirty-six female C57BL/6 mice were randomly divided into 3 groups ( n=12). Mice from sham group were only received the T 10 laminectomy. After the T 10 spinal cord injury (SCI) model was prepared in the SCI group and mitochondria transplantation (MT) group, mitochondrial storage solution and mitochondria (100 μg) derived from M2-like BV2 cells were injected into the injured segment, respectively. After operation, the Basso Mouse Scale (BMS) score was performed to evaluate the motor function recovery. And immunofluorescence staining, lycopersicon esculentum agglutinin (LEA)-FITC staining, and ELISA [vascular endothelial growth factor A (VEGFA)] were also performed. After polarization induction, BV2 cells in M1 and M2 groups showed specific morphological changes of M1-like and M2-like macrophages, respectively. Immunofluorescence staining showed that the positive expression of M2-like macrophages marker (Arg-1) was significantly higher in M2 group than in M0 group and M1 group ( P<0.05). Flow cytometry showed that the expression of M1-like macrophage marker (iNOS) was significantly higher in M1 group than in M0 group and M2 group ( P<0.05), and the expression of Arg-1 was significantly higher in M2 group than in M0 group and M1 group ( P<0.05). MitoSox Red and DCFH-DA stainings showed that the fluorescence intensity of the M2 group was significantly lower than that of the M1 group ( P<0.05), and there was no significant difference with the M0 group ( P>0.05). The M2-like BV2 cells-derived mitochondria was identified through Western blot assay. Animal experiments showed that the BMS scores of MT group at 21 and 28 days after operation were significantly higher than those of SCI group ( P<0.05). At 14 days after operation, the number of iNOS-positive cells in MT group was significantly lower than that in SCI group ( P<0.05), but still higher than that in sham group ( P<0.05); the number of LEA-positive cells and the expression of VEGFA in MT group were significantly more than those in the other two groups ( P<0.05). M2-like macrophage/microglia-derived mitochondria transplantation can promote angiogenesis and inhibit inflammatory M1-like macrophage/microglia polarization after mouse SCI to improve function recovery.

Abstract 6119: The Correlation analysis of driver genes of JAK-STAT signaling pathway with tumor immune microenvironment and prognosis in hepatocellular carcinoma

Abstract Background: The JAK/STAT pathway, which transmits signals that are crucial for growth, differentiation, immunity and survival, is altered in pan-cancer. And the downstream transcription factor STAT3 acts on the PD-L1 promoter and induced PD-L1 upregulation of in tumor. The roles of JAK-STAT signaling pathway in hepatocellular carcinoma (HCC), and its correlation with tumor immune microenvironment (TIME) and prognosis remain unclear. Method: 34 patients with HCC who underwent radical surgical resection at Southern Medical University Nanfang hospital were enrolled. Tumor tissue samples were collected for next generation sequencing (NGS) testing (733 genes panel) and multiple immunohistochemical fluorescence staining (mIHC). Clinical information was obtained to evaluate the prognostic performance of biomarkers. Whole exome sequencing data of 366 HCC patients was obtained from the Cancer Genome Altas (TCGA), and the tumor-related immune cells infiltration level difference between mutant and wild-type tumors were inferred using TIMER2.0. Results: Characteristics of 34 HCC patients from Nanfang cohort were as follows: 58.5% HBV positive, 41.2% largest tumor diameter≥5cm, 73.5% liver cirrhosis, 20.6% AFP &amp;gt; 400ng/ml, 67.6% MVI, 11.8% PVTT, 73.5% BCLC A, 85.3% CNLC I/II. 44% (15/34) HCC patients harboring JAK-STAT pathway related gene mutation, which EP300, STAT3 and JAK1 were the top three alternation frequency genes. The JAK-STAT pathway mutant tumors with significantly higher inferred M2 macrophages than wild-type (mean density, mutation vs. wild-type = 2.755 vs. 1.407 cells/mm2, p= 0.036). The level of infiltration of PD-L1 expression macrophages was significantly increased in the JAK - STAT pathway mutated tumors compared with wild-type tumors (p =0.048). After median follow-up time was 5.4 months, 3 short-term recurrence events were recorded. The recurrence-free survival (RFS) of EP300 and/or STAT3 mutation group (n=5) were longer than wild-type group (n=29) (median RFS, mutation vs. wild-type = 5.6 vs. NE months; HR 7.267[95% CI 0.46-113.8]; P = 0.057). While in TCGA cohort, the level of infiltration of M2 macrophages was increased in both STAT3 and EP300 mutant tumors compared with wild-type tumors (Wilcoxon test, p &amp;lt; 0.05). The significance of STAT3 and EP300 expression in cancer cells were evaluated on samples stratified by tumor-infiltrating macrophages M2 cells, which were divided into 4 groups respectively. Both RFS of high gene expression and high macrophages M2 groups were significantly different among the four groups (log-rank P&amp;lt;0.05). Conclusion: STAT3 and EP300 are driver genes of JAK-STAT signaling pathway in HCC. The JAK-STAT pathway mutation was associated with M2 macrophage infiltration and increased PD-L1 expression of macrophages, suggesting a poor prognosis. Citation Format: Dinghua Yang, Sheng Yu, Baitang Guo, Tingting Chen. The Correlation analysis of driver genes of JAK-STAT signaling pathway with tumor immune microenvironment and prognosis in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6119.

The intestinal microbiota influences the microenvironment of metastatic colon cancer by targeting miRNAs.

This study aimed to investigate the molecular mechanisms through which the intestinal microbiota and microRNAs (miRNAs) participate in colon cancer metastasis. Intestinal flora data, and the GSE29621 (messenger RNA/long non-coding RNA [mRNA/lncRNA]) and GSE29622 (miRNA) datasets, were downloaded from The Cancer Gene Atlas and Gene Expression Omnibus databases, respectively. Immune-related cells in M1 vs. M0 samples were analyzed using the Wilcoxon test. Furthermore, an lncRNA-miRNA-mRNA (competing endogenous RNA [ceRNA]) network was constructed, and survival analysis of RNAs in the network was performed. A total of 16 miRNA-genus co-expression pairs containing eight microbial genera and 15 miRNAs were screened; notably, Porphyromonas and Bifidobacterium spp. were found to be associated with most miRNAs, and has-miR-3943 was targeted by most microbial genera. Furthermore, five immune cell types, including activated natural killer cells, M1 macrophages, resting mast cells, activated mast cells and neutrophils, were differentially accumulated between the M1 and M0 groups. Enrichment analysis suggested that mRNAs related to colon cancer metastasis were mainly involved in pathways related to bacterial and immune responses. Survival analysis revealed that TMEM176A and PALM3 in the ceRNA network were significantly associated with the prognosis of patients with colon cancer. In conclusion, this study revealed a potential mechanism by which the intestinal microbiota influences the colon cancer microenvironment by targeting miRNAs.

Effect of low energy shock wave on testicular microenvironment homeostasis in rats

ObjectiveTo further investigate whether two sets of low-energy extracorporeal shock waves (LESWs) impulse parameters, i.e., 0.02 mJ/mm2 for 500 impulses and 0.04 mJ/mm2 for 500 impulses, which have been shown to directly affect the testes, can promote testicular spermatogenesis or positively regulate homeostasis of the testicular microenvironment. Methods(1) Twenty-four experimental rats were randomly divided into a 0.02 mJ/mm2 500 impulses group (L1 group), a 0.04 mJ/mm2 500 impulses group (M1 group), a sham intervention group (S group) and a blank control group (N group). The experiment period was 8 weeks. (2) Apoptosis of the spermatogenic cells in the left testicle was detected by the TUNEL method, VEGF and eNOs protein expression was detected by immunohistochemistry, and histomorphological changes were observed in PAS-stained sections. Moreover, the morphologies of the spermatogenic tubules and testicular stroma were quantitatively analyzed by stereological analysis. The right testicle was used for Western blot detection of the protein expression levels of Bax, Cytochrome C, Caspase-3, Bcl-2, VEGF and eNOs. ResultsCompared with the other three groups, the rate of M1 testicular germ cell apoptosis induced by shock treatment was higher, the expression levels of proapoptotic proteins increased significantly while that of the antiapoptotic protein was lower, and the suppression of cell proliferation correlated with the protein expression levels. Additionally, with respect to the absolute volume of the seminiferous tubules, the absolute interstitial testicular volume notably increased, producing a series of biological effects working against testicular sperm production and function. However, there was no significant difference between the L1 group and the N and S groups. ConclusionsLESWs treatment with impulse parameters of 0.02 mJ/mm2 for 500 impulses showed a better protective effect on testicular spermatic function in rats and has a positive regulatory biological effect.

A Retrospective Study of Lymph Node Dissection for Renal Cell Carcinoma

We retrospectively analyzed the effect of lymph node dissection (LND) in patients with renal cell carcinoma (RCC). Of 151 patients who underwent nephrectomy for RCC, 86 underwent LND. No distant metastasis (M0) was present in 71 patients, although distant metastasis (M1) was present in 15. Three (4.2%) and eight (53%) patients in the M0 and M1 groups, respectively, were clinical N-stage positive. Two (2.8%) and three (20%) patients in the M0 and M1 groups, respectively, were pathological N-stage positive. Both pathological N stage-positive patients in the M0 group were pathologically diagnosed with microphthalmia transcription family translocation RCC. The clinical and pathological positive node areas exhibited concordance in all three pathological N stage-positive patients in the M1 group. Chylous leakage occurred in 16 (19%) patients in the LND group (p＜0.05). Extended LND was a statistically significant risk factor for chylous leakage in the multivariate analysis. Only limited cases should undergo LND, owing to the low frequency of positive pathological lymph node metastasis, and high complication rate.

EVALUATION OF INTRANASAL MIDAZOLAM AS PREANESTHETIC MEDICATION FOR BRIEF PEDIATRIC SURGICAL PROCEDURES

Background: Operation theatres environment, surgery and anesthesia causes stress and anxiety. This can cause psychological disturbances especially in children. Sedative and anxiolytic premedication have been used to prevent such outcomes.Intranasal route is least traumatic and easily accepted.Intranasal midazolam has been used for premedication in children. Objectives:The study was undertaken to evaluate the efcacy of intranasal midazolam as premedication with regard to degree of sedation,ease of parental separation, response to venepuncture,response to induction,post anesthesia recovery charecteristics and side effects if any. Methods: A prospective comparative study was conducted in the Department of anesthesia viswabharathi medical college penchikalapadu, kurnool from November 2021 to may 2022 children aged between 3 - 6 years, of either sex belonging to ASA Grade I &amp; II posted for elective surgeries were selected randomly and prospective study was done by dividing them into 3 groups. Group NS: Children received 4.mI/kg of Normal Saline ,Group M1:Children received 0.2mg/kg of intranasal midazolam, Group M2: Children received 0.3mg/kg of intranasal midazolam. The statistical software, namely SPSS 16.0 and WINKS SDA 6 were used for the analysis of the data and Microsoft Word and Excel have been used to generate graphs, tables etc. : All the groups were comparable in age,sex,weight and ASA distribution.In midazolamResults M1 group 24(80%),in M2 group 22(65%) the children were dated.In midazolam M1 group,at 10minutes,parental separation in 27(90%).In M2 group,parental separation in 25(75%) children was much easier compared to 4(13.3%) in NS group.Response to venepuncture was more satisfactory in both midazolam groups than normal saline. Response to mask placement was also good in midazolam groups. There was no undue prolongation of recovery time in all the groups. : The study shows that intranasal midazolam 0.2mg/kg administered 15min prior toConclusion induction in children of 3-6years of age produces satisfactory level of sedation,ease of separation from parents, decreased discomfort associated with venepuncture with better mask acceptance. No signicant hemodynamic changes throughout the procedure.

Updated analysis of a prospective, randomized, controlled trial on the impact on clinical outcomes of fish oil supplementation during neoadjuvant chemoradiation for rectal cancer.

e15594 Background: The intake of nutritional supplements, such as fish oil, can modulate the inflammatory response and thus interfere with therapeutic results. Methods: Patients clinically staged as T3,4 and / or N + rectal adenocarcinoma were randomized 1:1 to receive oral ingestion four capsules, totaling 4g of concentrated fish oil (each gram of fish oil concentrate contained 1448 mg of Eicosapentaenoic acid (EPA) + 964 mg of docosahexaenoic acid (DHA)) throughout neoadjuvant conventional chemoradiation (intervention group – IG) or chemoradiation without supplement (control group – CG). All patients were operated about 8 weeks after chemoradiation. Correlation of inflammatory response - Glasgow Prognostic Score (GPS) with disease-free survival (DFS) was the primary outcome; measurements were collected at 4 moments: M1: at diagnosis; M2: at the end of chemoradiation; M3: at 4 weeks after end of chemoradiotherapy; and M4: preoperatively. Results: From January, 2015 and July, 2017, a total of 111 patients with cT3, 4 and / or N (+) rectal adenocarcinoma were accrued and randomized; 105 were randomized (IG: 51 and CG: 54). Mean age were 60 years, ranging from 30-86 years. There was no difference between groups in M1. In M2 and M3 there were differences between the IG and the CG in systemic inflammatory response measured by GPS (M2: p = 0.001; M3: p = 0.027). After neoadjuvant therapy, 49 patients in the CG and 46 patients in the IG were submitted to surgery; complete pathological response (pCR) was present in 15 patients in the CG and in 10 patients in the IG; there was no association of pCR and fish oil supplementation (P = 0.34). Median follow-up time was 45 months (range: 2-72). With a median follow up time of 24 months, DFS was shorter in patients with KPS &lt; 90% (47.0% vs 80.1%, P = 0.01), high risk (T4 or N+) rectal cancer (67.4% vs 89.7%, P = 0.01) and patients who did not achieve pCR after neoadjuvant CRT (65.5% vs 95.8%, P = 0.003). Also, shorter DFS was observed in patients with GPS 1 or 2 in M2 (69.1% vs 76.7%, p = 0.01) and M4 (38.9% vs 75.3%, p = 0.04) compared to patients with GPS 0 (reduced inflammatory response). In multivariate analysis, patients with high risk rectal cancer and GPS 1 or 2 in M2 had 3.07 and 2.11-fold greater risk of disease relapse; patients who achieved pCR had 84% reduction risk of DFS. KPS and GPS in M4 were not independent prognostic biomarkers for DFS. Conclusions: The oil fish supplementation during neoadjuvant chemoradiotherapy for rectal cancer was able to reduce the systemic inflammation syndrome (GPS = 0) associated with cancer. This reduction during treatment, especially in the preoperative moment was associated with better DFS. Thus, this intervention proposed in our study, as it is easily accessible and low cost, may be a viable strategy in this population and this finding should be better evaluate in future trials. Clinical trial information: NCT02534389.

Impact of intensive multimodal treatment on the outcomes of patients with anaplastic thyroid cancer.

6082 Background: Anaplastic thyroid cancer (ATC) is a rare and aggressive type of thyroid malignancy with very poor prognosis and outcome despite therapy. The rarity of this disease and the poor functional status of ATC patients limit the ability to conduct clinical trials, thus there is a lack of large, controlled trials to guide treatment and evaluate the benefit of combined modality therapy. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with ATC at age 18 or older between 2004 and 2018. After excluding patients with unknown number of treatment modalities, Charlson-Deyo score of 3 or more and patients lost follow-up, we split the cohort into three groups according to the number of treatment modalities they received. Treatment modalities include surgery, radiation, and systemic therapy. Then, we evaluated the overall survival (OS) between the three groups. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS. Additionally, propensity score matching (accounting for age, gender, race, Charlson-Deyo score, and clinical M stage) was used for more robust results. Results: A total of 3,460 patients with ATC were included in the analysis, of which 1,472 (42.5%) either received one type of therapy or did not receive any therapy (group1), 1,092 (31.6%) received bimodal therapy (group 2), and 896 (25.9%) received trimodal therapy (group 3). We found that group 3 had better OS compared to group 1 and group 2 (median OS 9.1 months vs 1.7 months and 4.9 months, respectively with P &lt; 0.001 for all). Propensity score matching yielded 896 patients in each group. We found that group 3 had better OS compared to group 1 and group 2 (median OS 9.1 months vs 1.9 months and 5.2 months, respectively with P &lt; 0.001 for all). Same trend was found in subgroup analysis when we split the cohort according to the metastatic status; in M0 group (median OS was 10.4 months vs 1.9 months and 6.1 months, respectively with P &lt; 0.001 for all), in M1 group (median OS was 5.9 months vs 1.4 months and 3.7 months, respectively with P &lt; 0.001 for all). On multivariate analysis, group 1 and group 2 were associated with worse OS compared to trimodal treatment (HR 2.721; 95% CI: 2.466 - 3.002 and HR 1.434; 95% CI: 1.299 - 1.582, P &lt; 0.001 for all). Conclusions: Patients with ATC who were treated with intensive trimodal therapy had statistically significant improvement in OS compared to patients who received less intense therapy. This survival benefit was observed in both metastatic and non-metastatic groups. While we acknowledge the limitations of this retrospective analysis, our results showed the critical role of intensive therapy approach in this aggressive malignancy.

Prognostic value of vessels encapsulating tumor clusters (VETC) in sarcoma.

e23523 Background: How sarcoma metastasize is unknown. VETC has been described as an epithelial-to-mesenchymal-transition independent process of metastasis: endothelium covers neoplastic clusters allowing tumor dissemination. It has also been shown to be a predictive of tyrosine kinase inhibitors (TKI) response. The objectives of the present study are: 1) to assess the presence of VETC in sarcoma; 2) to model its prognostic role. Methods: The study was retrospective. We selected 54 cases of sarcomas (6 DDLPS, 10 GIST, 6 retroperitoneal LMS, 9 MLPS, 8 MPNST, 10 SFT, 5 UPS); of them 31 were metastatic (M1 group), 23 were not (M0 group, defined as least 5 years of negative follow-up). High risk GIST and SFT, and grade 3 FNCLCC were considered high grade. VETC was assessed with CD31 immunohistochemistry and defined as a continuous endothelial lining around tumor clusters. We used Bayesian probabilistic modeling to detect small effects and multilevel hierarchical modeling to reduce overfitting. Models were fit using Stan and R. CI were computed with the HPDI method for 89%. The whole posterior probability (PP) was used for calculations. Results: The two groups (M0 &amp; M1) were substantially homogeneous: the CI of the contrast PP (CPP) included 0 in each histology for sex, age, size, and grade; VETC was more expressed in M1 SFT cases with almost all the CPP mass above the 0. Also, UPS and GIST showed VETC to be more present in metastatic diseases with 79% and 78% respectively of the CPP mass above 0 (see table). Metastasis free survival (MFS) analysis showed that VETC in SFT and UPS with a coefficient of 2.42 (CI 0.73 – 4.65) and 1.94 (CI 0.16 – 3.67); for the latter the median was reached with a PP density of median MFS of 65 months (mo) (standard deviation, SD: 74 mo) for VETC- Vs 11 mo (SD: 14 mo) for VETC+. Similarly, disease specific survival analysis showed – in SFT and UPS – that VETC was negatively associated with prognosis with coefficients of 1.24 and 2.34; however the CI covered slightly the 0 (-0.54 – 3.96 and -0.09 – 5.73, respectively). Conclusions: We found VETC in sarcoma and highlighted its prognostic role in SFT and UPS. [Table: see text]

The immunomodulatory effect of minocycline on gene expression of inflammation related cytokines in lipopolysaccharide-treated human peripheral blood mononuclear cells

To evaluate the immunomodulatory effect of minocycline, the present study was carried out on the gene expression of toll-like receptor type-4 (TLR4) and some pro-inflammatory (IL-1β, IL-6) and anti-inflammatory cytokines (IL-10) associated with lipopolysaccharide (LPS) -induced inflammation in human peripheral blood mononuclear cells (PBMCs). The PBMCs were collected and then 5.4 × 106 PBMCs/mL were used in eight groups as follows: control group (only media), LPS group (only LPS), methylprednisolone (Pred) group (LPS plus Pred), meloxicam (Melo) group (LPS plus Melo), three minocycline groups [M1, M5 and M25] (LPS plus 1, 5, and 25 µg/mL minocycline, respectively) and minocycline control (MC) group (5 µg/mL minocycline). After incubation for 24 h, the PBMCs were subjected to quantitative PCR assays. Gene expression levels of TLR4 were not changed in any groups. The IL-1β levels were increased in the LPS group but the increases were much more intense in the other groups except Pred group. Compared with control group, IL-6 levels increased significantly in Melo, M1 and M25 groups. Significant increases of IL-10 levels were also observed in Melo, M25 and MC groups. It can be concluded that minocycline had dual pro- and anti-inflammatory activities with potential clinical immunomodulatory effects.

Alternatively activated macrophages at the recipient site improve fat graft retention by promoting angiogenesis and adipogenesis.

The inflammatory response mediated by macrophages plays a role in tissue repair. Macrophages preferentially infiltrate the donor site and subsequently, infiltrate the recipient site after fat grafting. This study aimed to trace host‐derived macrophages and to evaluate the effects of macrophage infiltration at the recipient site during the early stage on long‐term fat graft retention. In our novel mouse model, all mice underwent simulated liposuction and were divided into 2 groups. The fat procurement plus grafting (Pro‐Grafting) group was engrafted with prepared fat (0.3 ml). The pro‐Grafting+M2 group was engrafted with prepared fat (0.3 ml) mixed with 1.0 × 106 GFP+M0 macrophages, and then, 2 ng IL‐4 was injected into the grafts on Day 3. In addition, 1.0 × 106 GFP+M0 macrophages were injected into the tail vein for tracing in the Pro‐Grafting group. As a result, GFP+macrophages first infiltrated the donor site and subsequently infiltrated the recipient site in the Pro‐Grafting group. The long‐term retention rate was higher in the Pro‐Grafting+M2 group (52% ± 6.5%) than in the Pro‐Grafting group (40% ± 3.5%). CD34+ and CD31+ areas were observed earlier, and expression of the adipogenic proteins PPAR‐γ, C/EBP and AP2 was higher in the Pro‐Grafting+M2 group than in the Pro‐Grafting group. The host macrophages preferentially infiltrate the donor site, and then, infiltrate the recipient site after fat grafting. At the early stage, an increase in macrophages at the recipient site may promote vascularization and regeneration, and thereby improve the fat graft retention rate.