Untangling determinants of gut microbiota and tumor immunologic status through a multi-omics approach in colorectal cancer.

The changes in gut microbiota have been implicated in colorectal cancer (CRC). The interplays between the host and gut microbiota remain largely unclear, and few studies have investigated these interplays using integrative multi-omics data. In this study, large-scale multi-comic datasets, including microbiome, metabolome, bulk transcriptomics and single cell RNA sequencing of CRC patients, were analyzed individually and integrated through advanced bioinformatics methods. We further examined the clinical relevance of these findings in the mice recolonized with microbiota from human. We found that CRC patients had distinct microbiota compositions compared to healthy controls. A machine-learning model was developed with 28 biomarkers for detection of CRC, which had high accuracy and clinical applicability. We identified multiple significant correlations between genera and well-characterized genes, suggesting the potential role of gut microbiota in tumor immunity. Further analysis showed that specific metabolites worked as profound communicators between these genera and tumor immunity. Integrating microbiota and metabolome perspectives, we cataloged gut taxonomic and metabolomic features that represented the key multi-omics signature of CRC. Furthermore, gut microbiota transplanted from CRC patients compromised the response of CRC to immunotherapy. These phenotypes were strongly associated with the alterations in gut microbiota, immune cell infiltration as well as multiple metabolic pathways. The comprehensive interplays across multi-comic data of CRC might explain how gut microbiota influenced tumor immunity. Hence, we proposed that modifying the CRC microbiota using healthy donors might serve as a promising strategy to improve response to immunotherapy.

Polyphyllin II Induces Protective Autophagy and Apoptosis via Inhibiting PI3K/AKT/mTOR and STAT3 Signaling in Colorectal Cancer Cells.

Polyphyllin II (PPII) is a natural steroidal saponin occurring in Rhizoma Paridis. It has been demonstrated to exhibit anti-cancer activity against a variety of cancer cells. However, the anti-colorectal cancer (CRC) effects and mechanism of action of PPII are rarely reported. In the present study, we showed that PPII inhibited the proliferation of HCT116 and SW620 cells. Moreover, PPII induced G2/M-phase cell cycle arrest and apoptosis, as well as protective autophagy, in CRC cells. We found that PPII-induced autophagy was associated with the inhibition of PI3K/AKT/mTOR signaling. Western blotting results further revealed that PPII lowered the protein levels of phospho-Src (Tyr416), phospho-JAK2 (Tyr1007/1008), phospho-STAT3 (Tyr705), and STAT3-targeted molecules in CRC cells. The overactivation of STAT3 attenuated the cytotoxicity of PPII against HCT116 cells, indicating the involvement of STAT3 inhibition in the anti-CRC effects of PPII. PPII (0.5 mg/kg or 1 mg/kg, i.p. once every 3 days) suppressed HCT116 tumor growth in nude mice. In alignment with the in vitro results, PPII inhibited proliferation, induced apoptosis, and lowered the protein levels of phospho-STAT3, phospho-AKT, and phospho-mTOR in xenografts. These data suggest that PPII could be a potent therapeutic agent for the treatment of CRC.

The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

Depression is increasingly recognized as an inflammatory disease, with inflammatory crosstalk in the brain contributing its pathogenesis. Life stresses may up-regulate inflammatory processes and promote depression. Although cytokines are central to stress-related immune responses, their contribution to stress-induced depression remains unclear. Here, we used unpredictable chronic mild stress (UCMS) to induce depression-like behaviors in mice, as assessed through a suite of behavioral tests. C-X-C motif chemokine ligand 1 (CXCL1)-related molecular networks responsible for depression-like behaviors were assessed through intrahippocampal microinjection of lenti-CXCL1, the antidepressant fluoxetine, the C-X-C motif chemokine receptor 2 (CXCR2) inhibitor SB265610, and the glycogen synthase kinase-3ß (GSK3ß) inhibitor AR-A014418. Modulation of apoptosis-related pathways and neuronal plasticity were assessed via quantification of cleaved caspase-3, B-cell lymphoma 2-associated X protein, cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) protein expression. CXCL1/CXCL2 expression was correlated with depression-like behaviors in response to chronic stress or antidepressant treatment in the UCMS depression model. Intrahippocampal microinjection of lenti-CXCL1 increased depression-like behaviors, activated GSK3ß, increased apoptosis pathways, suppressed CREB activation, and decreased BDNF. Administration of the selective GSK3ß inhibitor AR-A014418 abolished the effects of lenti-CXCL1, and the CXCR2 inhibitor SB265610 prevented chronic stress-induced depression-like behaviors, inhibited GSK3ß activity, blocked apoptosis pathways, and restored BDNF expression. The CXCL1/CXCR2 axis appears to play a critical role in stress-induced depression, and CXCR2 is a potential novel therapeutic target for patients with depression.-Chai, H.-H., Fu, X.-C., Ma, L., Sun, H.-T., Chen, G.-Z., Song, M.-Y., Chen, W.-X., Chen, Y.-S., Tan, M.-X., Guo, Y.-W., Li, S.-P. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice.

MRI-based nomogram estimates the risk of recurrence of primary nonmetastatic pancreatic neuroendocrine tumors after curative resection.

BACKGROUND: Accurate estimation of the recurrence of pancreatic neuroendocrine tumors help with prognosis, guide follow-up, and avoid futile treatments. PURPOSE: To investigate whether MRI features could preoperatively estimate the recurrence of pancreatic neuroendocrine tumors (PNETs) and to refine a novel prognostic model through developing a nomogram incorporating various MRI features. STUDY TYPE: Retrospective. POPULATION: In all, 81 patients with clinicopathologically confirmed nonmetastatic PNETs. FIELD STRENGTH/SEQUENCES: 1.5 T MR, including T1 -weighted, T2 -weighted, and diffusion-weighted imaging sequences. ASSESSMENT: Qualitative and quantitative MRI features of PNET were assessed by three experienced radiologists. STATISTICAL TESTS: Uni- and multivariable analyses for recurrence-free survival (RFS) were evaluated using a Cox proportional hazards model. The MRI-based nomogram was then designed based on multivariable logistic analysis in our study and the performance of the nomogram was validated according to C-index, calibration, and decision curve analyses. RESULTS: MRI features, including tumor size (hazard ratio [HR]: 14.131; P = 0.034), enhancement pattern (HR: 21.821, P = 0.032), and the apparent diffusion coefficient (ADC) values (HR: 0.055, P = 0.038) were significant independent predictors of RFS at multivariable analysis. The performance of the nomogram incorporating various MRI features (with a C-index of 0.910) was improved compared with that based on tumor size, enhancement pattern, and ADC alone (with C-index values of 0.672, 0.851, and 0.809, respectively). The calibration curve of the nomogram exhibited perfect consistency between estimation and observation at 0.5, 1, and 2 years after surgery. The decision curve showed that a nomogram incorporating three features had more favorable clinical predictive usefulness than any single feature. DATA CONCLUSION: MRI features can be considered effective recurrence predictors for PNETs after surgery. The preliminary nomogram incorporating various MRI features could assess the risk of recurrence in PNETs and may be used to optimize individual treatment strategies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:397-409.

[Effects of Biejiajian Pill on Proliferation and Apoptosis of Hepatic Stellate Cells in Mice].

Objective To observe the possible mechanism of Biejiajian Pill (BP) in fighting a- gainst hepatic fibrosis of hepatic stellate cell T6 ( HSC-T6) by studying effect of BP containing serum on inhibiting proliferation and inducing apoptosis of HSC-T6. Methods Forty Wistar rats were randomly di- vided into the negative control group (NC) , the positive drug control group (P) , high, middle, and low dose groups (H, M, L) , 8 in each group. BP suspension was administered by gastrogavage to rats in Group H, M, L at 21. 87, 43. 75, and 87. 50 mg/mL, respectively. Rats in Group NC were administered with equal volume of normal saline. Rats in Group P were administered with 0. 01 mg/mL colchicine solu- tion by gastrogavage. Each rat received 2 mL corresponding solution, twice per day, with an interval of 12 h gastrogavage, a total of 7 successive times to prepare drug containing serum. HSC-T6 cells were then randomly divided into drug containing serum groups (group H/M/L/NC) , colchicine positive control group (group P) , and the blank control group (BC). Cells in Group H/M/L/NC/P were fed with correspond- ing drug containing serums, while those in-Group BC were cultured with free drug serum. The proliferation inhibition rate of HSC-T6 was detected using CCK8 method at 24, 48, and 72 h, respectively. The apop- totic rate and cell cycle were detected using flow cytometry. Protein expressions of B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were detected using Western blot. Results Compared with Group NC, 24-h proliferation inhibition rate of HSC-T6 was obviously elevated in Group M, H, P (P < 0. 05). Compared with Group NC, 48- and 72-h proliferation inhibition rate of HSC-T6 was obviously ele- vated in Group L, M, H, P (P <0. 05). But there was no statistical difference in 24-, 48-, and 72-h prolif- eration inhibition rate of HSC-T6 among Group L, M, H, P (P >0. 05). Compared with Group NC and BC, early-and late-stage apoptosis rates of HSC-T6 obviously increased in Group M, H, P (P<0. 05) ; G,/G1 phase cell number obviously increased in Group M, H, P (P <0. 05) ; S phase and G2/M phase cell num- bers obviously decreased in Group L, M, H, P (P <0. 05). There was no statistical difference in Bcl-2 protein expression among each group (P>0. 05). Compared with Group NC, Bax protein expression ob- viously increased Group L, M, H, P (P <0. 01). Conclusion The mechanism of BP for fighting against hepatic fibrosis might be associated with inhibiting proliferation of HSC-T6 and inducing apoptosis.

Clinical efficacy of rhGM-CSF gel and medical collagen sponge on deep second-degree burns of infants: A randomized clinical trial.

BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSF + medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (P < .05). Bacterial positive rate was lower in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.

Three-Dimensional-Printed Template-Guided Radioactive Seed Brachytherapy via a Submental Approach for Recurrent Base of Tongue and Floor of Mouth Cancer.

Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.

Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

Neuron-Derived Exosomes Promote the Recovery of Spinal Cord Injury by Modulating Nerve Cells in the Cellular Microenvironment of the Lesion Area.

During spinal cord injury (SCI), the homeostasis of the cellular microenvironment in the injured area is seriously disrupted, which makes it extremely difficult for injured neurons with regenerative ability to repair, emphasizing the importance of restoring the cellular microenvironment at the injury site. Neurons interact closely with other nerve cells in the central nervous system (CNS) and regulate these cells. However, the specific mechanisms by which neurons modulate the cellular microenvironment remain unclear. Exosomes were isolated from the primary neurons, and their effects on astrocytes, microglia, oligodendrocyte progenitor cells (OPCs), neurons, and neural stem cells were investigated by quantifying the expression of related proteins and mRNA. A mouse SCI model was established, and neuron-derived exosomes were injected into the mice by the caudal vein to observe the recovery of motor function in mice and the changes in the nerve cells in the lesion area. Neuron-derived exosomes could reverse the activation of microglia and astrocytes and promote the maturation of OPCs in vivo and in vitro. In addition, neuron-derived exosomes promoted neurite outgrowth of neurons and the differentiation of neural stem cells into neurons. Moreover, our experiments showed that neuron-derived exosomes enhanced motor function recovery and nerve regeneration in mice with SCI. Our findings highlight that neuron-derived exosomes could promote the repair of the injured spinal cord by regulating the cellular microenvironment of neurons and could be a promising treatment for spinal cord injury.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

Bladder perforation injury after percutaneous peritoneal dialysis catheterization: A case report.

BACKGROUND: Insertion of a catheter into the bladder is a rare complication of peritoneal dialysis (PD), and is mainly related to surgical injury. This paper reports a case of bladder perforation that was caused by percutaneous PD catheterization. CASE SUMMARY: A 64-year-old man underwent percutaneous PD catheterization for end-stage renal disease. On the second day after the operation, urgent urination and gross hematuria occurred. Urinalysis showed the presence of red and white blood cells. Empirical anti-infective treatment was given. On the third day after the operation, urgent urination occurred during PD perfusion. Ultrasound showed that the PD catheter was located in the bladder, and subsequent computed tomography (CT) showed that the PD catheter moved through the anterior wall into the bladder. The PD catheter was withdrawn from the bladder and catheterization was retained. Repeat CT on the fourth day after the operation showed that the PD catheter was removed from the bladder, but there was poor catheter function. The PD catheter was removed and the patient was changed to hemodialysis. CT cystography showed that the bladder healed well and the patient was discharged 14 d after the operation. CONCLUSION: Bladder perforation injury should be considered and treated timeously in case of bladder irritation during and after percutaneous PD catheterization. The use of Doppler ultrasound and other related technologies may reduce the incidence of such complications.

Quercetin suppresses inflammatory cytokine production in rheumatoid arthritis fibroblast-like synoviocytes.

Rheumatoid arthritis (RA) is a chronic, progressive and systemic autoimmune disease mainly characterized by symmetric multijoint synovitis. Quercetin has anti-inflammatory, anti-oxidation and immune regulation activities, and therefore shows high medicinal value. The present study aimed to observe the effect of quercetin on fibroblast-like synoviocytes (FLSs) in RA. Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) were pretreated with 50 nmol/l quercetin for 2 h and were then stimulated using TNF-α for 24 h for subsequent experiments. RAFLSs were transfected with short interfering (si)-X-inactive specific transcript (XIST), microRNA (miR)-485 mimic, miR-485 inhibitor or si-PSMB8 or combination. ELISA, PCR and western blotting was used to evaluate the effect of quercetin on RAFLSs treated with TNF-α. It was revealed that quercetin inhibited the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Bioinformatics analysis indicated that XIST acted as a sponge for miR-485 and that proteasome subunit ß type-8 (PSMB8) was a direct target of miR-485. Moreover, PSMB8 functioned as a suppressor in inflammatory cytokine production of RAFLSs induced by TNF-α. Overall, quercetin was observed to inhibit the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Moreover, XIST-silencing could suppress the inflammatory reaction by sponging miR-485 in cells treated with TNF-α. Altogether, quercetin could suppress the development of RA in vitro.

Phosphorylcholine-Primed Dendritic Cells Aggravate the Development of Atherosclerosis in ApoE-/- Mice.

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×105 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE-/- mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.

Coupling interactions between sulfurous acid and the hydroperoxyl radical.

Radical-molecule complexes associated with the hydroperoxyl radical (HOO) play an important role in atmospheric chemistry. Herein, the nature of the coupling interactions between sulfurous acid (H(2)SO(3)) and the HOO radical is systematically investigated at the B3LYP/6-311++G(3df,3pd) level of theory in combination with the atoms in molecules (AIM) theory, the natural bond orbital (NBO) method, and energy decomposition analyses (EDA). Eight stable stationary points possessing double H-bonding features were located on the H(2)SO(3)...HOO potential energy surface. The largest binding energies of -12.27 and -11.72 kcal mol(-1) are observed for the two most stable complexes, where both of them possess strong double intermolecular H-bonds of partially covalence. Moreover, the characteristics of the IR spectra for the two most stable complexes are discussed to provide some help for their possible experimental identification.

[Correlation analysis on single nucleotide polymorphism of IL-23 receptor gene to susceptibility and clinical efficacy of recurrent oral ulcer].

PURPOSE: To investigate the correlation of gene polymorphisms of interleukin-23 receptor (IL-23R) rs11465817 and rs10489629 loci to susceptibility and clinical efficacy of recurrent oral ulcer (ROU). METHODS: A total of 150 ROU patients, who visited Stomatological Department of our hospital from January 2016 to December 2018, were selected as ROU group. A total of 150 healthy subjects who underwent physical examination at the same time in our hospital, were selected as healthy control group. Blood DNA was extracted from all subjects and amplified by polymerase chain reaction (PCR) at sites of IL-23R rs11465817 and rs10489629 loci. The genotyping was determined by electrophoresis after enzymatic digestion of amplified products. Patients with ROU were treated with oral levamisole, vitamin C, vitamin B2 and cetylpyridnium chloride gargle. Ulcer area and pain index were used to evaluate the clinical efficacy before and in the first week after treatment. Correlation on gene polymorphisms of interleukin-23 receptor (IL-23R) rs11465817 and rs10489629 loci to susceptibility and clinical efficacy of ROU was analyzed. SPSS 22.0 software package was used for statistical analysis of the data. RESULTS: Genotyping distribution of IL-23R rs11465817 and il-23r rs10489629 loci in healthy control group met Hardy-Weinberg equilibrium (P>0.05). Distribution frequency of CC and CA genotypes of IL-23R rs11465817 loci in ROU group was significantly higher than that in healthy control group (P<0.05), and logistic regression analysis showed that ROU risk in patients with CC and CA genotypes was significantly higher (P<0.05). The genotyping frequency of IL-23R rs10489629 loci was not significantly different between both groups (P>0.05). Logistic regression analysis showed that genotyping of IL-23R rs10489629 loci was not correlated with ROU sensitivity (P>0.05). The mean ulcer area and VAS score of ROU patients was significantly reduced after treatment (P<0.05). The ulcer area and VAS score in patients with IL-23R rs11465817 loci of AA genotype was significantly lower than that in patients with IL-23R rs11465817 loci of CC or CA genotype (P<0.05). Ulcer area and VAS score in patients with IL-23R rs10489629 locus of each genotype was not significantly different (P>0.05). CONCLUSIONS: Polymorphism of IL-23R rs11465817 loci is probably related to susceptibility and clinical efficacy of ROU, while polymorphism of IL-23R rs 10489629 is not probably related to susceptibility and clinical efficacy of ROU. The results of this study need to be further validated by a clinical study with large sample size.

Treatment of Whole-Plant Corn Silage With Lactic Acid Bacteria and Organic Acid Enhances Quality by Elevating Acid Content, Reducing pH, and Inhibiting Undesirable Microorganisms.

We investigated the variation in microbial community and fermentation characteristics of whole-plant corn silage after treatment with lactic acid bacteria (LAB) and organic acids. The fresh corn forages were treated with a combination of L. acidophilus and L. plantarum (106 CFU/g fresh material) or a 7:1:2 ratio of formic acid, acetic acid, and propionic acid (6 mL/g fresh material) followed by 45 or 90 days of ensiling. Silages treated with LAB showed increased lactic acid content and decreased pH after 45 days. Although treatment with LAB or organic acids decreased the common and unique operational taxonomic units, indicating a reduction in microbial diversity, the relative abundance of Lactobacillus was elevated after 45 and 90 days compared with control, which was more distinct in the organic acid groups. Moreover, we found higher levels of acetic acid and increased abundance of Acetobacter in silages treated with organic acids whereas undesirable microorganisms such as Klebsiella, Paenibacillus, and Enterobacter were reduced. In summary, the quality of corn silages was improved by LAB or organic acid treatment in which LAB more effectively enhanced lactic acid content and reduced pH while organic acid inhibited the growth of undesirable microorganisms.

[Effect of remifentanil preconditioning on myocardial ischemia-reperfusion injury].

OBJECTIVE: To investigate the delayed cardioprotection induced by remifentanil in intact rat ischemia-reperfusion (I/R) models. METHODS: Totally 42 adult male Wistar rats weighing 200-300 g were randomly divided into 7 groups (n = 6 in each group): In Group I, rats were injected with normal saline via tail vein, performed with the regimen of 3 x 5-min intravenous (i.v.) infusion at a rate of 0.1 ml x kg(-1) min(-1) 24 h before I/R; In Group II, rats were treated according to the same experimental protocols as in Group I except receiving additional naloxone (0.1 mg/kg) 10 minutes before normal saline pretreatment; In Groups III, IV, V, and VI, rats were treated with remifentanil via tail vein, performed with the regime of 3 x 5-min i.v. infusion at a rate of 2 microg x kg(-1) x min(-1) 12 h, 24 h, 48 h, and 72 h before I/R; In Group VII, the rats were treated according to the same experimental protocols as in Group IV except that they received additional naloxone (0.1 mg/kg) 10 minutes before remifentanil pretreatment. Heart rate (HR), mean arterial pressure (MAP), and a lead II electrocardiogram were continuously monitored during IR process. To determine plasma concentration of creatine kinase myocardial isoenzyme-MB (CK-MB), arterial blood samples were obtained immediately before ischemia, and at the end of ischemia and reperfusion. After a 120-min reperfusion, heart was removed for the measurement of myocardial infarct size. Infarct size (IS) was expressed as percentage of the area at risk. RESULTS: HR, MAP, and rate-pressure product were not significantly different at each time points among all groups (P > 0.05). Compared with Group I, plasma concentrations of CK-MB at the end of ischemia and reperfusion and myocardial infarct size were significantly lower in Groups IV and V (P < 0.05). Compared with Group IV, plasma concentrations of CK-MB at the end of ischemia and reperfusion were significantly higher and myocardial infarct size was significantly larger in Group VII (P < 0.05). CONCLUSION: Remifentanil preconditioning induces delayed cardioprotection in intact rat ischemia-reperfusion model, which may be triggered via opioid receptors.

Sulforaphane inhibits the activation of hepatic stellate cell by miRNA-423-5p targeting suppressor of fused.

Liver fibrosis, a common pathological process in chronic liver diseases, is characterized by excessive accumulation of extracellular matrix proteins and considered as a wound healing response to chronic liver injury. Hepatic stellate cell (HSC) activation plays a key role in liver fibrosis development. Previous studies showed that sulforaphane (SFN) has wide protective effects against tissue injury and inflammation. Accumulating evidence has shown that microRNAs play important roles in the development of hepatic fibrosis, some of which have been identified as potential therapeutic targets. This study was conducted to explore the role of SFN in the suppression of HSC activation. Quantitative real-time PCR showed that HSC miR-423-5p levels were up-regulated during HSC activation and down-regulated after SFN administration. Further, transfection of a miR-423-5p mimic demonstrated that inhibition of HSC activation by SFN required down-regulation of miR-423-5p. We showed that suppressor of fused is the direct target of miR-423-5p. SFN may play a role in inhibiting hepatic fibrosis by downregulating miRNA-423-5p. MiRNA-423-5p may be useful as a therapeutic target for treating hepatic fibrosis.

Assessing performance of augmented reality-based neurosurgical training.

This paper presents a novel augmented reality (AR)-based neurosurgical training simulator which provides a very natural way for surgeons to learn neurosurgical skills. Surgical simulation with bimanual haptic interaction is integrated in this work to provide a simulated environment for users to achieve holographic guidance for pre-operative training. To achieve the AR guidance, the simulator should precisely overlay the 3D anatomical information of the hidden target organs in the patients in real surgery. In this regard, the patient-specific anatomy structures are reconstructed from segmented brain magnetic resonance imaging. We propose a registration method for precise mapping of the virtual and real information. In addition, the simulator provides bimanual haptic interaction in a holographic environment to mimic real brain tumor resection. In this study, we conduct AR-based guidance validation and a user study on the developed simulator, which demonstrate the high accuracy of our AR-based neurosurgery simulator, as well as the AR guidance mode's potential to improve neurosurgery by simplifying the operation, reducing the difficulty of the operation, shortening the operation time, and increasing the precision of the operation.

A real-world 1:1 propensity-matched study revealed unmarried status was independently associated with worse survival for patients with renal clear cell carcinoma.

Background: Marital status has been reported as an independent prognostic factor for survival in various cancers, but it has been rarely studied in renal clear cell carcinoma (ccRCC). In this study, we aimed to assess the impact of marital status on the survival of ccRCC patients. Methods: We retrospectively investigated the Surveillance, Epidemiology, and End Results (SEER) database and identified 68599 of ccRCC patients between 1973 and 2015. These patients were divided into married, single, divorced and widowed groups. The survival differences among these groups were assessed by Kaplan-Meier method and log-rank test. Multivariate Cox regression analyses were performed to identify the overall survival (OS) and cancer-specific survival (CSS) independent factors. Furthermore, 1:1 propensity score matching (PSM) analysis was performed to minimize the potential confounding factors. Results: Of the 68599 ccRCC patients, 44553 (64.95%) patients were married, 7410 (10.80%) were divorced, 10663 (15.54%) were single, and 5973 (8.71%) were widowed. The 5-year OS was 79.0%, 73.8%, 77.3%, and 66.4 % in the married, divorced, single, and widowed groups, respectively (p = 0.001) and the corresponding 5-year CSS rates were 85.5%, 83.3%, 80.8%, 76.5%, respectively. Multivariate Cox regression analysis marital status was the independent prognostic factor for OS and CSS. Compared with the married patients, the divorced, single, and widowed patients faced increased higher mortality risks for OS and CSS. In stratified analyses by sex, surgery conditions and cancer stages, those unmarried patients still had worse prognosis. The results were further confirmed in the 1: 1 matched group. Conclusion: Unmarried ccRCC patients experienced worse survival than their married counterparts. Among the unmarried patients, the widowed suffered the highest mortality risks for OS and CSS.