Calycosin prevents NLRP3-induced gut fibrosis by regulating IL-33/ST2 axis.

Intestinal interstitial fibrosis is a core event of inflammatory bowel disease (IBD) development. Calycosin has been recognized to carry various therapeutic bioactivities. However, the role of calycosin in intestinal interstitial fibrosis remains to be illustrated. This aim of this study was to explore the effects of calycosin on intestinal interstitial fibrosis in IBD and the underlying mechanisms. The in vitro and in vivo models were established by using TNBS-induced mouse IBD model and co-culture of intestinal epithelial cells and intestinal interstitial cells; moreover, lentivirus-mediated knockdown of NLRP3 expression was applied. The results showed that calycosin significantly improved the intestinal interstitial fibrosis of TNBS-induced IBD. Mechanistically, calycosin downregulated NLRP3 expression and inhibited the activation of IL-33/ST2 signaling in intestinal epithelial cells, which subsequently impedes intestinal interstitial cell migration and activation by regulating the secretion of IL-33/ST2 signaling-induced fibrosis mediators. Notably, combination of calycosin and NLRP3 signaling blockade improved the intestinal interstitial fibrosis extent. Altogether, this study suggests calycosin can improve intestinal interstitial fibrosis by downregulating NLRP3-IL-33/ST2 signaling, reducing inflammation and decreasing pro-fibrotic factors' secretion, which provides a new perspective for therapeutic options of IBD.

A novel prognostic risk-scoring system based on m5C methylation regulator-mediated patterns for glioma patients.

N5-methylcytosine (m5C) methylation modification plays a crucial role in the epigenetic mechanisms underlying tumorigenesis, aggressiveness, and malignancy in diffuse glioma. Our study aimed to develop a novel prognostic risk-scoring system to assess the impact of m5C modification in glioma patients. Initially, we identified two distinct m5C clusters based on the expression level of m5C regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two m5C cluster groups were determined. Utilizing these m5C regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an m5C scoring system was developed through a univariate Cox regression model, quantifying the m5C modification patterns utilizing six DEGs associated with disease prognosis. The resulting scoring system allowed us to categorize patients into high- or low-risk groups based on their m5C scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher m5C score consistently exhibited shorter survival durations, fewer isocitrate dehydrogenase (IDH) mutations, less 1p/19q codeletion and higher World Health Organization (WHO) grades. Additionally, distinct immune cell infiltration characteristics were observed among different m5C cluster groups and risk groups. Our study developed a novel prognostic scoring system based on m5C modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.

Primary Surgery Followed by Selective Chemoradiotherapy Versus Preoperative Chemoradiotherapy Followed by Surgery for Locally Advanced Rectal Cancer: A Randomized Clinical Trial.

PURPOSE: The aim of this work was to determine whether locally advanced rectal cancer (LARC) with negative mesorectal fascia (MRF) predicted by magnetic resonance imaging (MRI) can be excluded from preoperative radiation therapy treatment. METHODS AND MATERIALS: This multicenter, open-label, non-inferiority, randomized clinical trial enrolled patients with LARC within 6 to 12 cm from the anal verge and with negative MRI-predicted MRF. Participants were randomized to the intervention group (primary surgery, in which the patients with positive pathologic [CRM] circumferential margins were subjected to chemoradiotherapy [CRT] and those with negative CRM underwent adjuvant chemotherapy according to pathologic staging) or the control group (preoperative CRT, in which all patients underwent subsequent surgery and adjuvant chemotherapy). The primary endpoint was 3-year disease-free survival (DFS). RESULTS: A total of 275 patients were randomly assigned to the intervention (n = 140) and control (n = 135) groups, in which 33.57% and 28.15% patients were at clinical T4 stage and 85.92% and 80.45% patients were at "bad" or "ugly" risk in the intervention and control groups, respectively. There were 2 patients (1.52%) and 1 patient (0.77%) with positive CRM in the intervention and control groups, respectively (P > .05). The non-adherence rates for the intervention and control groups were 3.6% and 23.7%, respectively. After a median follow-up of 34.6 months (IQR, 18.2-45.7), 43 patients had positive events (28 patients and 15 patients in the intervention and control groups, respectively). There were 6 patients (4.4%) with local recurrence in the intervention group and none in the control group, which led to the termination of the trial. The 3-year DFS rate was 81.82% in the intervention group (95% CI, 78.18%-85.46%) and 85.37% in the control group (95% CI, 81.75%-88.99%), with a difference of -3.55% (95% CI, -3.71% to -3.39%; hazard ratio, 1.76; 95% CI, 0.94-3.30). In the per-protocol data set, the difference between 3-year DFS rates was -5.44% (95% CI, -5.63% to -5.25%; hazard ratio, 2.02; 95% CI, 1.01-4.06). CONCLUSIONS: Based on the outcomes of this trial, in patients with LARC and MRI-negative MRF, primary surgery could negatively influence their DFS rates. Therefore, primary surgery was an inferior strategy compared with preoperative CRT followed by surgery and cannot be recommended for patients with LARC.

Activation of Beta-adrenergic Receptors Upregulates the Signal-to-Noise Ratio of Auditory Input in the Medial Prefrontal Cortex and Mediates Auditory Fear Conditioning.

Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. We aimed to investigate whether the activation of the ß-adrenergic receptor (ß-AR) improves AFC by sensitization of the prelimbic (PL) cortex at the animal, cellular, and molecular levels. In vivo single-cell electrophysiological recording was used to characterize the changes in neurons in the PL cortex after AFC. Then, PL neurons were locally administrated by the ß-AR agonist isoproterenol (ISO), the GABAaR agonist muscimol, or intervened by optogenetic method, respectively. Western blotting and immunohistochemistry were finally used to assess molecular changes. Noise and low-frequency tones induced similar AFC. The expression of ß-ARs in PL cortex neurons was upregulated after fear conditioning. Microinjection of muscimol into the PL cortex blocked the conformation of AFC, whereas ISO injection facilitated AFC. Moreover, PL neurons can be distinguished into two types, with type I but not type II neurons responding to conditioned sound and being regulated by ß-ARs. Our results showed that ß-ARs in the PL cortex regulate conditional fear learning by activating type I PL neurons.

SYNJ1 rescues motor functions in hereditary and sporadic Parkinson's disease mice by upregulating TSP-1 expression.

This study aimed to explore the role of SYNJ1 in Parkinson's disease (PD) and its potential as a neuroprotective factor. We found that SYNJ1 was decreased in the SN and striatum of hSNCA*A53T-Tg and MPTP-induced mice compared to normal mice, associated with motor dysfunction, increased α-synuclein and decreased tyrosine hydroxylase. To investigate its neuroprotective effects, SYNJ1 expression was upregulated in the striatum of mice through injection of the rAdV-Synj1 virus into the striatum, which resulted in the rescue of behavioral deficiencies and amelioration of pathological changes. Subsequently, transcriptomic sequencing, bioinformatics analysis and qPCR were conducted in SH-SY5Y cells following SYNJ1 gene knockdown to identify its downstream pathways, which revealed decreased expression of TSP-1 involving extracellular matrix pathways. The virtual protein-protein docking further suggested a potential interaction between the SYNJ1 and TSP-1 proteins. This was followed by the identification of a SYNJ1-dependent TSP-1 expression model in two PD models. The coimmunoprecipitation experiment verified that the interaction between SYNJ1 and TSP-1 was attenuated in 11-month-old hSNCA*A53T-Tg mice compared to normal controls. Our findings suggest that overexpression of SYNJ1 may protect hSNCA*A53T-Tg and MPTP-induced mice by upregulating TSP-1 expression, which is involved in the extracellular matrix pathways. This suggests that SYNJ1 could be a potential therapeutic target for PD, though more research is needed to understand its mechanism.

Integrin αvß6 contributes to the development of intestinal fibrosis via the FAK/AKT signaling pathway.

Intestinal fibrosis is one of the most severe complications of inflammatory bowel disease (IBD) and frequently requires surgery due to intestinal obstruction. Integrin αvß6, which is mainly regulated by the integrin ß6 subunit gene (ITGB6), is a special integrin subtype expressed only in epithelial cells. In our previous study, we found integrin αvß6 can promote the development of IBD, but the role of integrin αvß6 in intestinal fibrosis remains unclear. In this study, we observed a gradual increase of ITGB6 mRNA expression from normal region to stenotic region of IBD patients' intestinal specimens. Next, we established a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and a heterotopic intestinal transplant model, and found intestinal fibrosis was decreased in ITGB6-deficient mice compared to wild-type (WT) mice. Furthermore, we performed RNA-sequencing and KEGG pathway analysis on intestinal tissues from ITGB6-overexpressing transgenic mice and WT mice, and found multiple pathways containing ITGB6, are related to the activation of focal adhesion kinase (FAK); finding was confirmed by Western blot. At last, we generated a heterotopic intestinal transplant model found the FAK/AKT pathway was inhibited in ITGB6-deficient mice. In conclusion, our data demonstrate that integrin αvß6 promotes the pathogenesis of intestinal fibrosis by FAK/AKT pathway, making integrin αvß6 a potential therapeutic target to prevent this condition.

Transgenic overexpression of ITGB6 in intestinal epithelial cells exacerbates dextran sulfate sodium-induced colitis in mice.

Integrins, as a large family of cell adhesion molecules, play a crucial role in maintaining intestinal homeostasis. In inflammatory bowel disease (IBD), homeostasis is disrupted. Integrin αvß6, which is mainly regulated by the integrin ß6 subunit gene (ITGB6), is a cell adhesion molecule that mediates cell-cell and cell-matrix interactions. However, the role of ITGB6 in the pathogenesis of IBD remains elusive. In this study, we found that ITGB6 was markedly upregulated in inflamed intestinal tissues from patients with IBD. Then, we generated an intestinal epithelial cell-specific ITGB6 transgenic mouse model. Conditional ITGB6 transgene expression exacerbated experimental colitis in mouse models of acute and chronic dextran sulphate sodium (DSS)-induced colitis. Survival analyses revealed that ITGB6 transgene expression correlated with poor prognosis in DSS-induced colitis. Furthermore, our data indicated that ITGB6 transgene expression increased macrophages infiltration, pro-inflammatory cytokines secretion, integrin ligands expression and Stat1 signalling pathway activation. Collectively, our findings revealed a previously unknown role of ITGB6 in IBD and highlighted the possibility of ITGB6 as a diagnostic marker and therapeutic target for IBD.

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

Auditory Fear Conditioning Alters Sensitivity of the Medial Prefrontal Cortex but this is not based on Frequency-dependent Integration.

Although many studies have shown that the prelimbic (PL) cortex of the mPFC is involved in the formation of conditioned freezing behavior, few have considered the acoustic response characteristics of PL cortex. Importantly, the change in auditory response characteristics of the PL cortex after conditional fear learning is largely unknown. Here we used in vivo cell-attached recordings targeting the mPFC during the waking state. We confirmed that the mPFC of adult C57 mice have neurons that respond to noise and tone in the waking state, especially in the PL cortex. Interestingly, the data also confirmed that these neurons responded well to the intensity of sound but did not have frequency topological distribution characteristics. Furthermore, we found that the number of c-fos positive neurons in the PL cortex increased significantly after auditory fear conditioning. The auditory-induced local field potential recordings and in vivo cell-attached recordings demonstrated that the PL cortex was more sensitive to the auditory conditioned stimulus after the acquisition of conditioned fear. The proportion of neurons responding to noise was significantly increased, and the signal to noise ratio of the spikes were also increased. These data reveal that PL neurons themselves responded to the main information (sound intensity), while the secondary information (frequency) response was almost negligible after auditory fear conditioning. This phenomenon may be the functional basis for handling this type of emotional memory, and this response characteristic is thought to be emotional sensitization but does not change the nature of this response.

Electrical Performance and Bias-Stress Stability of Amorphous InGaZnO Thin-Film Transistors with Buried-Channel Layers.

To improve the electrical performance and bias-stress stability of amorphous InGaZnO thin-film transistors (a-IGZO TFTs), we fabricated and characterized buried-channel devices with multiple-stacked channel layers, i.e., a nitrogen-doped a-IGZO film (front-channel layer), a conventional a-IGZO film (buried-channel layer), and a nitrogen-doped a-IGZO film (back-channel layer). The larger field-effect mobility (5.8 cm2V-1s-1), the smaller subthreshold swing value (0.8 V/dec, and the better stability (smaller threshold voltage shifts during bias-stress and light illumination tests) were obtained for the buried-channel device relative to the conventional a-IGZO TFT. The specially designed channel-layer structure resulted in multiple conduction channels and hence large field-effect mobility. The in situ nitrogen-doping caused reductions in both the front-channel interface trap density and the density of deep states in the bulk channel layers, leading to a small subthreshold swing value. The better stability properties may be related to both the reduced trap states by nitrogen-doping and the passivation effect of the nitrogen-doped a-IGZO films at the device back channels.

SP1-induced lncRNA TINCR overexpression contributes to colorectal cancer progression by sponging miR-7-5p.

Mounting evidences have indicated that long noncoding RNAs (lncRNAs) play pivotal roles in human diseases, especially in cancers. Recently, TINCR was proposed to be involved in tumor progression. However, its role in colorectal cancer (CRC) remains elusive. In our study, we found that SP1-induced TINCR was significantly upregulated in CRC tissues and cell lines. Moreover, cox multivariate survival analysis revealed that high TINCR was an independent predictor of poor overall survival (OS). Functionally, knockdown of TINCR obviously suppressed CRC cells proliferation, migration and invasion in vitro, and inhibited CRC cells growth and metastasis in vivo. Mechanistically, we identified TINCR could act as a miR-7-5p sponge using RNA pull down, luciferase reporter and RIP assays. Furthermore, we showed that TINCR might promote CRC progression via miR-7-5p-mediated PI3K/Akt/mTOR signaling pathway. Lastly, we revealed that plasma TINCR expression was upregulated in CRC when compared to healthy controls and could be a promising diagnostic biomarker for CRC. Based on above results, our data indicated that TINCR might serve as a potential diagnostic and prognostic biomarker for CRC.

The Combination of Human Urinary Kallidinogenase and Mild Hypothermia Protects Adult Rats Against Hypoxic-Ischemic Encephalopathy-Induced Injury by Promoting Angiogenesis and Regeneration.

Objectives: Human Urinary Kallidinogenase (HUK) is a tissue kallikrein that plays neuroprotective role in ischemic conditions via different mechanisms. Mild hypothermia (MH) is another robust neuroprotectant that reduces mortality but does not profoundly ameliorate the neurological outcome in hypoxic-ischemic encephalopathy (HIE) patients. However, whether the combination of HUK and MH can be used as a promising neuroprotective treatment in HIE is unknown. Methods: One-hundred and forty-four adult Wistar rats were randomly divided into five groups: Sham, HIE, HUK, MH and a combination of HUK and MH treatment. The HIE rat model was established by right carotid dissection followed by hypoxia aspiration. The survival curve was created within 7 days, and the neurological severity scores (NSS) were assessed at days 0, 1, 3, and 7. Nissl staining, Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), immunofluorescent staining and western blotting were used to evaluate neuronal survival, apoptosis and necrosis, tight-junction proteins Claudin-1 and Zonula occludens-1 (ZO-1), vascular endothelial growth factor (VEGF), doublecortex (DCX), bradykinin receptor B1 (BDKRB1), BDKRB2 and Ki67 staining. Results: The combined treatment rescued all HIE rats from death and had a best survival curve compared to HIE. The Combination also reduced the NSS scores after HIE at days 7, better than HUK or MH alone. The combination of HUK and MH reserved more cells in Nissl staining and inhibited neuronal apoptosis and necrosis as well as significantly attenuated HIE-induced decreases in claudin-1, ZO-1, cyclin D1 and BDKRB1/B2 in comparison to HUK or MH treatment alone. Moreover, the combined treatment increased the expression of VEGF and DCX as well as the number of Ki67-labeled cells. Conclusions: This study demonstrates that both HUK and MH are neuroprotective after HIE insult; however, the combined therapy with HUK and MH enhanced the efficiency and efficacy of either therapy alone in the treatment of HIE, at least partially by promoting angiogenesis and regeneration and rescuing tight-junction loss. The combination of HUK and MH seems to be a feasible and promising clinical strategy to alleviate cerebral injury following HIE insult. Highlights: -The combination of HUK and MH distinctly reduces neurological dysfunction in HIE rats.-HUK enhances the neuroprotective effects of MH in HIE.-MH attenuates tight-junction disruption, upregulates the BDKR B1/2, DCX and cyclin D1.-The combination of MH and HUK enhances the expressions of MH/HUK mediated-BDKR B1/2, DCX, cyclin D1 and Ki67 positive cells.

Glia maturation factor-ß: a potential therapeutic target in neurodegeneration and neuroinflammation.

Glia maturation factor-ß (GMFB) is considered to be a growth and differentiation factor for both glia and neurons. GMFB has been found to be upregulated in several neuroinflammation and neurodegeneration conditions. It may function by mediating apoptosis and by modulating the expression of superoxide dismutase, granulocyte-macrophage colony-stimulating factor, and neurotrophin. In this review, we mainly discussed the role of GMFB in several neuroinflammatory and neurodegenerative diseases. On review of the literature, we propose that GMFB may be a promising therapeutic target for neuroinflammatory and neurodegenerative diseases.

MicroRNA­663 suppresses the proliferation and invasion of colorectal cancer cells by directly targeting FSCN1.

Colorectal cancer (CRC) is the most frequently diagnosed malignancy of the gastrointestinal tract. The dysregulation of microRNAs (miRNAs/miRs) has been reported in the majority of types of human cancer, and is correlated with tumorigenesis and tumor development. Abnormal expression of miR­663 has been observed in various types of human cancer. However, little is known about its role in CRC. Therefore, the aim of the present study was to clarify the expression and potential role of miR­663, and its underlying molecular mechanism in CRC. It was observed that miR­663 was markedly downregulated in CRC tissues and cell lines. Decreased miR­663 expression levels in CRC tissues were correlated with tumor, node, metastasis stage and lymph node metastasis. Functional assays revealed that upregulation of miR­663 inhibited cell proliferation and invasion in CRC. Further molecular mechanism assays demonstrated the fascin (FSCN1) was a target gene of miR­663. In addition, FSCN1 was increased and negatively correlated with miR­663 expression in CRC tissues. FSCN1 underexpression mimicked the tumor suppressive functions induced by miR­663 overexpression on CRC cell proliferation and invasion. Collectively, the present study presented evidence that miR­663 may act as a tumor suppressor in CRC by directly targeting FSCN1, which may lead to a potential therapeutic strategy focusing on miR­663 and FSCN1 for patients with this disease.

Continuous intrathecal administration of liposomal amphotericin B for treatment of refractory Cryptococcus neoformans encephalitis: A case report.

The aim of the present study was to investigate the treatment of refractory Cryptococcus neoformans encephalitis with continuous administration of liposomal amphotericin B (AmB). Liposomal AmB was administered to a 28-year-old male by intravenous injection, with daily increasing dosages up to 150 mg per day and combined use of fluconazole (0.4 g per day) and oral flucytosine tablets (1.5 g per day). Following 5 months of treatment, C. neoformans could still be detected in the ink stain of cerebrospinal fluid, but the patient could not tolerate a further increase in the dosage of liposomal AmB. Instead, continuous intrathecal administration of AmB through tube drainage on the lumbar cistern was used. A total dosage of 28 mg liposomal AmB was administered to the patient over the course of 1 month. The effect of AmB administered by intravenous injection was not as great as expected and the patient's tolerance was not good. However, the patient recovered following treatment by continuous intrathecal administration of AmB through tube drainage on the lumbar cistern for 1 month. This case suggests that continuous intrathecal administration of liposomal AmB should be considered for clinical treatment of refractory cryptococcal encephalitis.

Kennedy disease with difficulty in differential diagnosis: A case report.

RATIONALE: Kennedy disease (KD) is also known as spinal bulbar muscular dystrophy. As KD has similar symptoms with most neuromuscular diseases, so it is difficult to make a rapid diagnosis clinically. PATIENT CONCERNS: We report a case of a 43-year-old male with progressive limb proximal weakness without family history. Physical examination showed gynecomastia, erectile dysfunction, bilateral tendon reflex and quadriceps weakness, and tongue muscle atrophy. DIAGNOSES: Laboratory examination found increased creatine kinase, impaired glucose tolerance, and abnormal lactic acid values. There was no mutation or copy number variant in SMN1 gene and related mitochondrion genes tested, even with the use of multiplex ligation probe- dependent amplification technique. Diagnosis was confirmed with genetic analysis which displayed trinucleotide CAG (glutamine)- repeat expansion in the androgen-receptor gene. INTERVENTIONS AND OUTCOMES: The patient achieved good prognosis with symptomatic treatment after diagnosis. LESSONS: To diagnose KD, clinicians should pay more attention to differentiate KD and myasthenia gravis, mitochondrial myopathy, and amyotrophic lateral sclerosis. Gene analysis was the key in detecting this rare confusing disease in the patient.

[Clinical significance of hypersensitive C-reactive protein, fribrinogen and D-dimmer in connective tissue disease-related interstitial lung disease].

OBJECTIVE: To investigate the clinical significance of plasma levels of hypersensitive C-reactive protein (hs-CRP), fibriogen and D-dimmer (D-DI) in patients with connective tissue disease (CTD)-related interstitial lung disease (CTD-ILD). METHODS: Sixty-nine patients with interstitial lung disease admitted in Zhujiang Hospital between January, 2010 and April, 2016, including 29 with CTD-ILD and 40 with non-CTD-ILD were analyzed for plasma levels of hs-CRP, fibriogen and D-DI, with 25 healthy subjects as the control group. RESULTS: The plasma level of hs-CRP, fibriogen and D-DI in patients with CTD-ILD and non-CTD-ILD were all significantly higher than those in the control group. The patients with CTD-ILD had a significantly higher hs-CRP level than those with non-CTD-ILD, but the levels of fibriogen and D-DI were comparable between the two groups. Correlation analysis indicated that Hs-CRP level was positively correlated with the levels of D-DI (r=0.539, P<0.01) and fibrinogen (r=0.534, P<0.01). CONCLUSION: Hs-CRP, fibriogen and D-DI levels show an important value in clinical diagnosis of CTD, and an obvious elevation of hs-CRP is correlated with the CTD.

The Relationship between Neutrophil-to-Lymphocyte Ratio and Intracerebral Hemorrhage in Type 2 Diabetes Mellitus.

INTRODUCTION: Chronic systematic inflammation has been suggested to be associated with the occurrence and development of cardiovascular events. Low-grade systematic inflammation persists in type 2 diabetes mellitus (T2DM) patients. In addition, the risk of cerebral hemorrhage in these patients is increased compared with non-diabetic patients. Neutrophil-to-lymphocyte ratio (NLR) is the ratio derived by dividing the neutrophil count with the lymphocyte count from a peripheral blood sample. This study aimed to explore the relation between NLR and cerebral hemorrhage, and to prove that NLR is an independent risk factor of cerebral hemorrhage in T2DM patients. METHODS: In total, 429 cases of T2DM patients were included. The patients were divided into two groups depending on the presence of cerebral hemorrhage: the cerebral hemorrhage group (n = 87) and the control group (n = 342). Based on clinical and laboratory data of diabetes diagnosis, this article investigates the relationship between NLR and the risk of cerebral hemorrhage. RESULTS: Increase in NLR was positively correlated with the incidence of cerebral hemorrhage in T2DM patients and might serve as an independent risk factor of cerebral hemorrhage in T2DM patients (OR: 4.451, 95% CI: 2.582-7.672). NLR >2.58 might be useful in predicting the threshold value of cerebral hemorrhage risk in newly diagnosed T2DM patients (area under the curve: .72, 95% CI: .659-.780, P < .001) CONCLUSION: As an indicator of the degree of systematic inflammation, NLR is an independent risk factor of cerebral hemorrhage in T2DM patients.

[Risk factor analysis on postoperative complications after laparoscopic total mesorectal excision with preventive terminal ileostomy and timing of stoma closure in rectal cancer].

OBJECTIVE: To summarize the application of protective terminal ileostomy in laparoscopic total mesorectal excision for rectal cancer patients, and explore the risk factors associated with postoperative complications and timing of stoma closure. METHODS: Clinical data of 77 patients with middle or low rectal cancer undergoing laparoscopic total mesorectal excision (TME) with preventive terminal ileostomy in our department from January 2007 to December 2013 were retrospectively analyzed. Independent risk factors associated to postoperative complications of terminal ileostomy were examined by logistic regression and timing of stoma closure was investigated. RESULT: The total postoperative complication morbidity was 57.1% (44/77). Electrolyte disturbance was found in 39 cases (50.6%, 39/77), including 1 case of hypovolemic syncope. Parastomal hernia occurred in 9 cases (11.7%, 9/77). Peristomal dermatitis and subcutaneous abscess was observed in 1 case (1.3%, 1/77). The result of the single factor analysis of the water electrolyte disturbance after operation, the risk factors of P<0.2 were new adjuvant chemotherapy (P=0.094), tumor antigen (P=0.086) and TNM staging (P=0.026); Postoperative parastomal hernia of the single factor analysis results, the risk factors of P<0.2 included uses of antidiabetic drugs (P=0.172), ASA anesthesia (P=0.168) grading and TNM stage(P=0.161); But multivariate analysis revealed no risk factors associated with the above complications (all P>0.05). Sixty-five patients underwent stoma closure during follow-up, including 2 cases (3.1%) within 90 days, 20 cases (30.8%) from 90 to 180 days, and 43 cases (66.2%) more than 180 days. CONCLUSIONS: No risk factors were found to be associated with main postoperative complications of protective terminal ileostomy after laparoscopic TME for rectal cancer patients, such as electrolytes imbalance and parastomal hernia. The timing of stoma closure should be longer than 180 days.