Recently, small nucleolar RNAs (snoRNAs) have transcended the genomic "noise" to emerge as pivotal molecular markers due to their essential roles in tumor progression. Substantial evidence indicates a strong association between snoRNAs and critical clinical features such as tumor pathology and drug resistance. Historically, snoRNA research has concentrated on two classical mechanisms: 2'-O-ribose methylation and pseudouridylation. This review specifically summarizes the novel regulatory mechanisms and functional patterns of snoRNAs in tumors, encompassing transcriptional, post-transcriptional, and post-translational regulation. We further discuss the synergistic effect between snoRNA host genes (SNHGs) and snoRNAs in tumor progression. More importantly, snoRNAs extensively contribute to the development of tumor cell resistance as oncogenes or tumor suppressor genes. Accordingly, we provide a comprehensive review of the clinical diagnosis and treatment associated with snoRNAs and explore their significant potential as novel drug targets.

Objective:To investigate the mechanism of resolvin D1 (RvD1) in alleviating brain injury after cardiopulmonary resuscitation (CPR) through regulating autophagy pathway in pigs.Methods:Nineteen male domestic pigs, weighing 30-41 kg, were divided into 3 groups using a random number table method: sham group (S group, n=5), CPR group ( n=7), and RvD1 group ( n=7). In the S group, the animals only experienced general preparation. In the CPR and RvD1 groups, the pig CPR model was established by 8 min of cardiac arrest caused by electrically induced ventricular fibrillation, and followed by 5 min of CPR. At 5 min after resuscitation, a dose of 0.6 μg/kg of resolvin D1 was injected via femoral vein in the RvD1 group, and the same amount of vehicle was similarly administered in the other two groups. At 1, 3, 6, and 24 h after resuscitation, blood samples were collected from the femoral vein to measure serum concentrations of neuron specific enolase (NSE) and S100β protein by ELISA. At 24 h after resuscitation, neurological function was evaluated by neurological deficit score (NDS), and then the animals were euthanized to obtain cerebral cortex for measuring the expressions of phosphorylated AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of rapamycin (p-mTOR), microtubule-associated protein light chain 3 (LC3 II) and p62 by Western blot. The variables were compared with One-way analysis of variance and then the Bonferroni test among the three groups. Results:During 24 h after resuscitation, the NDS was significantly increased accompanied with significantly greater concentrations of NSE and S100β in serum in the CPR and RvD1 groups compared to the S group (all P<0.05). However, the NDS was significantly decreased at 24 h after resuscitation [(182±34) vs.(124±18), P<0.05], and serum NSE and S100β were significantly reduced starting 3 h after resuscitation in the RvD1 group compared to the CPR group [NSE (ng/mL): (23.1±3.8) vs. (18.0±2.2) at 3 h, (27.3±2.9) vs. (19.8±1.4) at 6 h, and (28.1±1.3) vs. (15.1±2.1) at 24 h; S100B (pg/mL): (1 611±208) vs. (1 322±100) at 3 h, (1 825±197) vs. (1 410±102) at 6 h, and (1 613±138) vs. (1 183±139) at 24 h, all P<0.05]. The expression levels of p-AMPK and LC3 II were significantly increased while the expression levels of p-mTOR and p62 were significantly decreased at 24 h after resuscitation in the CPR and RvD1 groups compared to the S group (all P<0.05). However, the expression levels of p-AMPK and LC3 II were significantly lower and the expression levels of p-mTOR and p62 were significantly higher at 24 h after resuscitation in the RvD1 group compared to the CPR group [p-AMPK: (0.28±0.08) vs. (0.17±0.03); LC3 II: (0.33±0.09) vs. (0.21±0.04); p-mTOR: (0.13±0.02) vs. (0.16±0.02); p62: (0.16±0.05) vs. (0.22±0.02), all P<0.05]. Conclusions:The protective mechanism by which RvD1 alleviates brain injury after CPR in pigs might be related to the inhibition of neuronal autophagy mediated by AMPK/mTOR pathway.

Objective:To evaluate the clinical value of neutrophil/lymphocyte ratio (NLR) in early prediction of the incidence of sepsis-induced organ dysfunction and 28-day mortality.Methods:A retrospective study was conducted in 815 adult patients with sepsis admitted to the department of critical care medicine of the First Affiliated Hospital of China Medical University from January 2017 to December 2019. The clinical data including age, gender and complication were collected, and the peripheral blood routine indexes at 24, 48 and 72 hours after the diagnosis of sepsis were collected, and the NLR was calculated. The primary endpoint of the study was the incidences of sepsis related acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and acute liver failure (ALF); the secondary endpoint was the 28-day in-hospital mortality in septic patients with organ dysfunction. Univariate and multivariate Logistic regression were used to analyze the risk factors of organ dysfunction and 28-day mortality in patients with sepsis, the receiver operating characteristic curve (ROC curve) was drawn and the area under the ROC curve (AUC) was calculated to evaluate the predictive value of NLR for organ dysfunction and 28-day mortality in patients with sepsis.Results:A total of 714 patients with sepsis were enrolled for final statistical analysis. There was no significant difference in NLR at 24, 48 and 72 hours in patients with or without organ dysfunction (such as AKI, ARDS, DIC and ALF). Logistic regression analysis showed that there was no significant difference in NLR at 24 hours with 28-day in-hospital mortality [odds ratio ( OR) = 1.006, 95% confidence interval (95% CI) was 0.994-1.019, P = 0.323]. However, NLR at 48 hours and 72 hours had a significant difference with 28-day mortality (48 hours: OR = 1.026, 95% CI was 1.013-1.040, P = 0.000; 72 hours: OR = 1.021, 95% CI was 1.005-1.037, P = 0.010), which suggested that NLR at 48 hours and 72 hours after diagnosis were independent risks factor for 28-day mortality in patients with sepsis. ROC curve showed that the AUC of NLR at 48 hours was 0.598, 95% CI was 0.540-0.658, P = 0.02; when the cut-off value was 10.1, the sensitivity and specificity for predicting 28-day mortality was 75.2% and 58.0%, respectively; the AUC of NLR at 72 hours was 0.595, 95% CI was 0.536-0.655, P = 0.03; when the cut-off value was 9.24, the sensitivity and specificity for predicting 28-day mortality was 75.3% and 59.9%, respectively. Conclusions:NLR cannot predict the occurrence of AKI, ARDS, DIC and ALF in sepsis in early stage. NLR has a certain clinical value in predicting 28-day mortality in patients with sepsis, but its predictive efficiency is low.

Neutrophil extracellular traps (NETs) are net-like structure composed of DNA and nuclear proteins, which are produced by activated neutrophils under the circumstances of a variety of pathogens or drugs. As part of defensive mechanism, NETs have been proved to restrict the spread of pathogens and release of antimicrobial molecules. NETs can not only strengthen the adhesion between neutrophils and platelets, promote platelet mediated procoagulant reaction, but also lead to endothelial cell damage and coagulopathy in sepsis. In addition, NETs also plays an important role in pathophysiological processes of venous thrombosis. Therefore, NETs may become the biomarkers of evaluating coagulation dysfunction and potential therapy target in sepsis.

Objective To investigate the changes of neutrophil extracellular traps (NETs) level in plasma of sepsis patients and judge its clinical value for early diagnosing of sepsis.Methods A prospective observational study was conducted. The patients after surgery aged > 18 years and expected to stay in the ICU > 24 hours admitted to intensive care unit (ICU) of the First Affiliated Hospital of China Medical University from November 2014 to February 2015 were enrolled. According to the criteria of sepsis diagnosis in 1991, patients were divided into non-sepsis group and sepsis group. The healthy people who taken a physical examination were enrolled in the healthy control group. 3 mL peripheral venous blood was collected at 1 hour after admission to ICU. A fasting blood was collected in the healthy control group in the morning. The plasma free DNA (cf-DNA/NETs) was determined by using the fluorescence microplate reader, white blood cell (WBC), neutrophil ratio (NEU), procalcitonin (PCT), C-reactiveprotein (CRP) in peripheral blood of the patients were detected, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The correlation between plasma NETs and the risk factors in sepsis patients was analyzed by Spearman correlation analysis. The value of cf-DNA/NETs and WBC level in the diagnosis of sepsis was analyzed by using the receiver operating characteristic curve (ROC).Results Twenty-three sepsis patients, 20 non-sepsis patients, and 22 healthy persons were enrolled. There were no differences in baseline variables including gender and age among three groups, which indicated baseline data equalization. The plasma concentration of cf-DNA/NETs in sepsis group was significantly higher than that in non-sepsis group and healthy control group (μg/L: 453.44±185.37 vs. 188.35±29.66, 203.83±43.25, bothP < 0.05),and there was no significant difference between last two groups (P > 0.05). WBC, NEU, PCT, CRP, APACHE Ⅱ and SOFA score in sepsis group were significantly higher than those of non-sepsis group [WBC (×109/L): 9.52±5.51 vs. 5.97±2.28, NEU: 0.787±0.110 vs. 0.655±0.067, PCT (mg/L): 7.14 (3.60, 13.29) vs. 6.07 (3.57, 7.91), CRP (mg/L): 64.44±13.14 vs. 27.00±19.47, APACHE Ⅱ: 10.25±4.92 vs. 6.00±1.22, SOFA: 6.0±5.1 vs. 5.0±1.2, allP < 0.05]. Correlation analysis showed that the level of NETs had no obvious correlation with gender, age, WBC, NEU, PCT, CRP, APACHE Ⅱ and SOFA scores (r value was 0.322, 0.262, 0.194, 0.312, 0.227, 0.454, 0.433, 0.333, respectively, allP > 0.05). The area under the ROC curve (AUC) of plasma cf-DNA/NETs for the diagnosis of sepsis was 0.981. When the cut-off valueof plasma cf-DNA/NETs was > 257.96μg/L, the sensitivity was 91.3%, specialty was 95.2%, and Youden index was 0.865. AUC of WBC in the diagnosis of sepsis was 0.663. When the cut-off value of WBC was > 6.0×109/L, the sensitivity was 78.3% and specificity was 25.0%.Conclusion The plasma cf-DNA/NETs levels increased significantly in sepsis patients. In the diagnosis of sepsis, plasma NETs levels had better advantages over WBC. NETs can be used as a biomarker for early diagnosis of sepsis.

Objective To investigate the influence of heparin pretreatment on serum and lung tissue level of neutrophil extracellular traps (NETs) in septic mice model and its molecular mechanism.Methods Ninety male C57BL/6J mice were randomly divided into control group (n = 30), lipopolysaccharides (LPS) group (n = 30, 30 mg/kg LPS in 100μL normal saline was intraperitoneally injected) and LPS+heparin group (n = 30, 8 U of heparin in 20μL normal saline was subcutaneously injected 30 minutes before the injection of LPS). Six hours later of LPS injection, blood was collected and lung tissue was harvested. Enzyme linked immunosorbent assay (ELISA) was used to assess the concentration of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and histones 2AX (H2AX), neutrophil elastase (NE), which reflected NETs concentration. PicoGreen fluorescent dyes was used to detect serum circulating free DNA (cf-DNA/NETs) concentration. The protein expression levels of H2AX and NE in lung tissue were examined by Western Blot.Results The serum concentrations of TNF-α, IL-6, H2AX, NE, cf-DNA/NETs, and the protein expression levels of H2AX and NE in lung tissue of septic mice were significantly higher than those of control group [TNF-α (ng/L): 133.0±14.1 vs. 2.7±1.0, IL-6 (ng/L): 3911.2±189.2 vs. 298.9±52.5, H2AX (ng/L): 545.5±40.0 vs. 21.9±8.3, NE (μg/L): 6.48±0.12 vs. 0.47±0.15, cf-DNA/NETs (μg/L): 846.3±137.5 vs. 152.7±36.4, H2AX protein (gray value): 1.14±0.09 vs. 0.68±0.04, NE protein (gray value): 0.56±0.03 vs. 0.32±0.04, allP < 0.05]. After heparin pretreatment, levels of serum TNF-α, H2AX, NE, cf-DNA/NETs, and protein expression levels of H2AX and NE in lung tissue were significantly reduced [TNF-α (ng/L): 83.2±7.6 vs. 133.0±14.1, H2AX (ng/L): 435.0±39.0 vs. 545.5±40.0, NE (μg/L): 4.26±0.17 vs. 6.48±0.12, cf-DNA/NETs (μg/L): 606.5±73.9 vs. 846.3±137.5, H2AX protein (gray value): 0.91±0.03 vs. 1.14±0.09, NE protein (gray value): 0.42±0.03 vs. 0.56±0.03, allP < 0.05], but no significant change was found in IL-6 (ng/L: 3919.9±166.6 vs. 3911.2±189.2,P > 0.05).Conclusion Heparin pretreatment could significantly decrease the level of NETs in serum and lung tissue, and can be the potential mechanism of its organ protection in sepsis.

Objective To analyze the clinical features of renal involvement associated with Behcet's disease (BD) through 1 case and to make a review of the literature in order to early diagnose and cure in time,thus decrease misdiagnosis and mistreatment.Methods This is a retrospective study.The case was diagnosed with BD and the renal damage was confirmed by renal biopsy.The clinical features and histology features were analyzed.Results The presentation of renal disease was edema,proteinuria and microscopic hematuria.The clinical spectrum of renal BD showed a wide variation.Amyloidosis (AA type),GN (nephritis),and microscopic vascular disease were the main causes of renal BD.Patients with vascular involvement had a high risk of amyloidosis and amyloidosis was the most common cause of renal failure in BD.Conclusion Kidney is one of the organs that can alter the prognosis of the BD,so the screening for renal damage must be done for each patient with this disease.Routine urine analysis and measurement of serum creatinine level are needed for early diagnosis of renal BD.Immunosuppressive drugs can be useful in selected cases.

Objective To study the CT findings of small thyroid carcinoma. Methods The CT findings of 40 patients with histology-proven small thyroid carcinoma (diameter, 1.0 to 2. 0 cm) were retrospectively reviewed. Results (1)The single lesion was detected in 38 cases and two lesions in bilateral thyroid in 2 cases. Two cases were combined with contralateral nodular goiter and I case with contralateral thyroid adenoma. ( 2 ) Eight lesions showed smooth edge and complete envelope. Thirty-four lesions demonstrated foggy edge and incomplete envelope,but they didn't invade the surrounding soft tissues and important organs. ( 3 ) The density of all lesions were homogeneous or comparatively homogeneous without obvious hemorrhage or necrosis area on non-enhanced CT. Thirty lesions showed varied shape calcifications,with granular calcifications in 20 lesions being the most common. Irregular nodular,eggshell-like or mulberrylike calcifications were also detected. (4)Forty-one lesions showed marked enhancement on post-contrast CT and the amplitude of enhanced CT value was greater than 40 HU(range,90 to 140 HU). Thirty-eight lesions exhibited homogeneous enhancement, and other 3 lesions showed marked enhancement center with a ring-like low density edge and manifested as a characteristic damascene-like appearance. (5)Enlarged cervical lymph nodes were found in 24 cases ( 60. 0% ), which displayed solid, cystic-solid or cystic appearances on nonenhanced CT. They showed markedly homogeneous,irregular ring or wall-node enhancement on post-contrast CT. In 8 cases there were granular, nodular or eggshell-like calcifications within the enlarged lymph nodes.Conclusion A solid thyroid nodule with granular calcification, incomplete envelope and marked enhancement, companied with enlarged lymph nodes with calcification, cystic degeneration and obviously enhanced solid part are the relatively characteristic CT features of small thyroid carcinoma.