Whole exome sequencing and MicroRNA profiling of lung adenocarcinoma identified risk prediction features for tumors at stage I and its substages.

OBJECTIVES: About 20% of stage I lung adenocarcinoma (LUAD) patients suffer a relapse after surgical resection. While finer substages have been defined and refined in the AJCC staging system, clinical investigations on the tumor molecular landscape are lacking. MATERIALS AND METHODS: We performed whole exome sequencing, DNA copy number and microRNA profiling on paired tumor-normal samples from a cohort of 113 treatment-naïve stage I Taiwanese LUAD patients. We searched for molecular features associated with relapse-free survival (RFS) of stage I or its substages and validated the findings with an independent Caucasian LUAD cohort. RESULTS: We found sixteen nonsynonymous mutations harbored at EGFR, KRAS, TP53, CTNNB1 and six other genes associated with poor RFS in a dose-dependent manner via variant allele fraction (VAF). An index, maxVAF, was constructed to quantify the overall mutation load from genes other than EGFR. High maxVAF scores discriminated a small group of high-risk LUAD at stage I (median RFS: 4.5 versus 69.5 months; HR = 10.5, 95% CI = 4.22-26.12, P < 0.001). At the substage level, higher risk was found for patients with high maxVAF or high miR-31; IA (median RFS: 32.1 versus 122.8 months, P = 0.005) and IB (median RFS: 7.1 versus 26.2, P = 0.049). MicroRNAs, miR-182, miR-183 and miR-196a were found correlated with EGFR mutation and poor RFS in stage IB patients. CONCLUSION: Distinctive features of somatic gene mutation and microRNA expression of stage I LUAD are characterized to complement the survival prognosis by substaging. The findings open up more options for precision management of stage I LUAD patients.

Long-term outcomes of lateral vocal fold autologous fat injection for unilateral vocal fold paralysis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the long-term outcomes of patients with unilateral vocal fold paralysis resulting in dysphonia treated with lateral vocal fold autologous fat injection. To analyze the factors that may affect the long-term efficacy of the procedure. Methods: From July 2003 to June 2020, 163 patients (86 males and 77 females), aged 9-73 years (mean (34.50±12.94) years) with unilateral vocal fold paralysis resulting in dysphonia underwent transoral laryngoscopic injection of autologous fat into the lateral vocal folds. Subjective auditory perception assessment (GRBAS scale), objective acoustic assessment, voice handicap index (VHI) evaluation and stroboscopic laryngoscopy were compared before and after the surgery. Patients were followed up for 1 to 18 years, with median follow-up time of 6 years. SPSS 22.0 software was used for statistical analysis. Results: Of 163 patients, 17 patients (10.4%) had mild hoarseness (G1) and 146 patients (89.6%) had moderate to severe hoarseness (G2-3). Stroboscopic laryngoscopy revealed an arch-shaped vocal fold on the affected side, fixed in the paramedian position or abduction position, with obvious glottic closure fissure. Postoperatively, voice recovered to normal (G0) in 139 patients (85.3%), mild hoarseness (G1) in 18 patients (11.0%) and moderate hoarseness (G2) in 6 patients (3.7%). Of these, 131 patients (80.4%) showed significant improvement in hoarseness, 29 patients (17.8%) showed mild improvement and 3 patients (1.8%) showed no significant improvement in hoarseness. Objective acoustic parameters of Jitter, Shimmer, NHR and MPT improved significantly, as did VHI scores. Stroboscopic laryngoscopy showed medialization of the affected vocal folds, improved vocal fold closure and normal or nearly normal vocal fold mucosal waves. With a fat injection volume of 3.0-4.5 ml, the patient's subjective auditory perception scores of G, R, B and A improved more significantly within 3 months after surgery, and both VHI and MPT were significantly better since 1 year after surgery. With bilateral vocal fold injection, the B and A scores improved significantly from 1 month postoperatively compared to unilateral injections(unilateral vs. bilateral injection 1 month post-operation, tB scores=1.42,tA scores=1.51,P<0.05). Conclusions: The long-term efficacy of autologous fat injection in the paraglottic space for the treatment of unilateral vocal fold paralysis was stable. The efficacy of the surgery was related to the amount of fat injected, unilateral or bilateral of the injection.

[Plasma components of Danzhi Xiaoyao Formula and its mechanism of action in treating perimenopausal depression based on UPLC-Q-TOF-MS~E integrated with network pharmacology].

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.

Factors Associated with Postoperative Lipiduria and Hypoxemia in Patients Undergoing Surgery for Orthopedic Fractures.

We investigated factors associated with postoperative lipiduria and hypoxemia in patients undergoing surgery for orthopedic fractures. We enrolled patients who presented to our emergency department due to traumatic fractures between 2016 and 2017. We collected urine samples within 24 h after the patients had undergone surgery to determine the presence of lipiduria. Hypoxemia was defined as an SpO2 <95% determined with a pulse oximeter during the hospitalization. Patients' anthropometric data, medical history, and laboratory test results were collected from the electronic medical record. Logistic regression analyses were used to determine the associations of clinical factors with postoperative lipiduria and hypoxemia with multivariate adjustments. A total of 144 patients were analyzed (mean age 51.3 ± 22.9 years, male 50.7%). Diabetes (odd ratio 3.684, 95% CI, 1.256-10.810, p = 0.018) and operation time (odd ratio 1.005, 95% CI, 1.000-1.009, p = 0.029) were independently associated with postoperative lipiduria, while age (odd ratio 1.034, 95% CI, 1.003-1.066, p = 0.029), body mass index (odd ratio 1.100, 95% CI, 1.007-1.203, p = 0.035), and operation time (odd ratio 1.005, 95% CI, 1.000-1.010, p = 0.033) were independently associated with postoperative hypoxemia. We identified several factors independently associated with postoperative lipiduria and hypoxemia in patients with fracture undergoing surgical intervention. Operation time was associated with both postoperative lipiduria and hypoxemia, and we recommend that patients with prolonged operation for fractures should be carefully monitored for clinical signs related to fat embolism syndrome.

Enhanced Optical Response of Zinc-Doped Tin Disulfide Layered Crystals Grown with the Chemical Vapor Transport Method.

Tin disulfide (SnS2) is a promising semiconductor for use in nanoelectronics and optoelectronics. Doping plays an essential role in SnS2 applications, because it can increase the functionality of SnS2 by tuning its original properties. In this study, the effect of zinc (Zn) doping on the photoelectric characteristics of SnS2 crystals was explored. The chemical vapor transport method was adopted to grow pristine and Zn-doped SnS2 crystals. Scanning electron microscopy images indicated that the grown SnS2 crystals were layered materials. The ratio of the normalized photocurrent of the Zn-doped specimen to that of the pristine specimen increased with an increasing illumination frequency, reaching approximately five at 104 Hz. Time-resolved photocurrent measurements revealed that the Zn-doped specimen had shorter rise and fall times and a higher current amplitude than the pristine specimen. The photoresponsivity of the specimens increased with an increasing bias voltage or decreasing laser power. The Zn-doped SnS2 crystals had 7.18 and 3.44 times higher photoresponsivity, respectively, than the pristine crystals at a bias voltage of 20 V and a laser power of 4 × 10-8 W. The experimental results of this study indicate that Zn doping markedly enhances the optical response of SnS2 layered crystals.

Study on changes of voice characteristics after adenotonsillectomy or adenoidectomy in children / 中华耳鼻咽喉头颈外科杂志

Objective: To study voice changes in children after adenotonsillectomy or adenoidectomy and the relationship with the vocal tract structure. Methods: Fifty patients were recruited in this study prospectively, aged from 4 to 12 years old with the median age of 6. They were underwent adenotonsillectomy or adenoidectomy in Beijing Tongren Hospital, Capital Medical University from July 2019 to August 2020. In the cases, there are 31 males and 19 females. Thirty-six patients underwent adenotonsillectomy and 14 patients underwent adenoidectomy alone. Twenty-two children (13 males, 9 females) with Ⅰ degree of bilateral tonsils without adenoid hypertrophy and no snoring were selected as normal controls. Adenoid and tonsil sizes were evaluated. Subjective changes of voice were recorded after surgery. Moreover, voice data including fundamental frequency(F0), jitter, shimmer, noise to harmonic ratio(NHR), maximum phonation time(MPT), formant frequencies(F1-F5) and bandwidths(B1-B5) of vowel/a/and/i/were analyzed before, 3 days and 1 month after surgery respectively.SPSS 23.0 was used for statistical analysis. Results: Thirty-six patients(72.0%,36/50) complained of postoperative voice changes. The incidence was inversely correlated with age. In children aged 4-6, 7-9, and 10-12, the incidence was 83.3%(25/30), 63.6%(7/11) and 44.4%(4/9) respectively. Voice changes appeared more common in children underwent adenotonsillectomy(77.8%,28/36) than in those underwent adenoidectomy alone(57.1%,8/14), but there was no statistical difference. After operation, for vowel/a/, MPT(Z=2.18,P=0.041) and F2(t=2.13,P=0.040) increased, B2(Z=2.04,P=0.041) and B4(Z=2.00,P=0.046) decreased. For vowel/i/, F2(t=2.035,P=0.050) and F4(t=4.44,P=0.0001) increased, B2(Z=2.36,P=0.019) decreased. Other acoustic parameters were not significantly different from those before surgery. The F2(r=-0.392, P =0.032) of vowel/a/and F2(r=-0.279, P=0.048) and F4 (r=-0.401, P =0.028) of vowel/i/after adenotonsillectomy were significantly higher than those of adenoidectomy alone. Half of patients with postopertive voice changes can recover spontaneously 1 month after surgery. Conclusions: Voice changes in children underwent adenotonsillectomy or adenoidectomy might be related to their changes in formants and bandwidths. The effect of adenotonsillectomy on voice was more significant compared with that of adenoidectomy alone. The acoustic parameters did not change significantly after surgery except MPT.

Application of deep convolutional neural networks in the diagnosis of laryngeal squamous cell carcinoma based on narrow band imaging endoscopy / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the possibility of using artificial intelligence (AI) technology based on convolutional neural network (CNN) to assist the clinical diagnosis of laryngeal squamous cell carcinoma (LSCC) through deep learning algorithm. Methods: A deep CNN was developed and applied in narrow band imaging (NBI) endoscopy of 4 799 patients with laryngeal lesions, including 3 168 males and 1 631 females, aged from 21 to 87 years, from 2015 to 2017 in Beijing Tongren Hospital, Capital Medical University. A simple randomization method was used to select the laryngeal NBI images of 2 427 patients (1 388 benign lesions and 1 039 LSCC lesions) for the training and correction the CNN model. The remaining laryngeal NBI images of 2 372 patients (including 1 276 benign lesions and 1 096 LSCC lesions) were used as validation data set to compare performance between CNN and otolaryngologists. SPSS 21.0 software was used for Chi-square test to calculate the accuracy, sensitivity and specificity of AI and otolaryngologists. The area under the curve (AUC) of receiver operating curve (ROC) was used to evaluate the diagnostic ability of the algorithm for NBI images. Results: The accuracy, sensitivity and specificity for NBI predictions were respectively 90.91% (AUC=0.96), 90.12% and 91.53%, which were equivalent to those for otolaryngologists' predictions (accuracy, sensitivity and specificity were (91.93±3.20)%, (91.33±3.25)% and (93.02±2.59)%, t values were 0.64, 0.75 and 1.17, and P values were 0.32, 0.28 and 0.21, respectively). The diagnostic efficiency of CNN was significantly higher than that of otolaryngologists (0.01 vs. 5.50, t =9.15, P<0.001). Conclusion: AI based on deep CNN is effective for using in the laryngeal NBI image diagnosis, showing a good application prospect in the diagnosis of LSCC.

Diagnosis and endoscopic treatment of blunt laryngeal trauma with arytenoid injury / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical characteristics, diagnosis, endoscopic surgical procedures, and therapeutic effect of blunt laryngeal trauma with arytenoid injury. Methods: We retrospectively reviewed 12 patients who suffered blunt laryngeal trauma with laryngeal mucosa avulsion and arytenoid region injury at the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital from April 2007 to December 2018. Among the 12 patients, 10 were males, 2 were females, aged from 7 to 48 years old, with a median age of 21 years old. All patients were performed with transoral endoscopic laryngeal microsurgery under general anesthesia. Clinical characteristics, laryngoscopic signs, laryngeal CT, endoscopic surgical findings and procedures, and therapeutic effect were analyzed. The subjective and objective parameters of the voice quality of patients before and after surgery were compared using SPSS 22.0 statistical software by paired T test. Results: All patients had a history of obvious dysphonia immediately after trauma, accompanied by throat pain and hemoptysis without obvious dyspnea and dysphagia. Slight subcutaneous emphysema was found in 3 patients by physical examination. Laryngoscope revealed that 14 sides of vocal folds immobilized, arytenoid and/or ventricular region and posterior glottis mucosa were avulsed in 4 patients within 48 h of injury, and arytenoid cartilage was exposed in 4 sides. The arytenoid and ventricular regions were covered with thick pseudo-membrane or granulation, with abnormal structure in 8 patients with damage of more than 48 h. Intraoperative exploration revealed that there were 17 sides of arytenoid region (bilateral 5 cases, unilateral 7 cases) with varying degrees of injury. There was only limited laceration on three sides of the vocal folds. The lateral ventricular and vocal fold mucosae were avulsed vertically from the arytenoid region and arytenoid cartilage was exposed in 14 sides, among which 6 sides had abnormal arytenoid cartilage morphology and 8 sides had fracture displacement. Laryngeal CT showed irregular thickening of lateral glottis and/or supratroglottic structures in patients with vocal folds immobility, among which asymmetry of arytenoid cartilage structure on both sides in 3 cases and displacement in 2 cases were found. Restoration and microsuture of the fractured arytenoid, perichondrium and avulsion laryngeal mucosa under the direct laryngoscope were performed. The degree of dysphonia was significantly improved immediately after laryngeal microsurgery, the voice significantly improved in G, R, B, A, jitter, shimmer, NHR, and MPT three months after surgery(t=12.792, 12.792, 10.340, 3.276, 2.865, 3.781, 3.173, 3.090, respectively, P<0.05). Except for 1 patient with scar on vocal fold, all the other patients had normal laryngeal morphology and normal vocal fold movement. No laryngeal stenosis was found during the follow-up period. Conclusions: For patients with blunt laryngeal trauma, the injury of arytenoid region and arytenoid cartilage should be evaluated if there is obvious hoarseness, vocal fold immobility, avulsion of ventricular/vocal folds mucosa, or structural abnormality of arytenoid region under laryngoscopic examination. For highly suspected cases, microrphonosurgery under the direct laryngoscope should be performed as soon as possible, which can effectively reduce the occurrence of vocal fold movement disorders and laryngeal scar/stenosis, reconstruct the normal laryngeal structure, and restore the vocal function.

Effects of resveratrol on the levels of ATP, 5-HT and GAP-43 in the hippocampus of mice exposed to chronic unpredictable mild stress.

Growing evidence suggested that energy deficiency might be involved in the pathophysiological mechanism of depression. Energy deficiency, mainly results from mitochondrial damage, can lead to the dysfunction of synaptic neurotransmission, and further cause depressive-like behavior. The antidepressant effect of resveratrol had been widely demonstrated in previous studies; however, the underlying mechanism remains poorly understood. The present study aimed to investigate whether the antidepressant effects of resveratrol involved in the energy levels and neurotransmission in the hippocampus. We found that resveratrol and fluoxetine significantly attenuated depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which evidenced by the increased sucrose preference and the reduced immobility time in a forced swimming test. In addition, resveratrol increased hippocampal ATP levels, decreased Na+-K+-ATPase and pyruvate levels, and upregulated the levels of mitochondrial DNA (mtDNA), mRNA expression of sirtuin (SIRT)1 and peroxisome proliferator-activated receptor γ coactivator (PGC)1α. Furthermore, resveratrol and fluoxetine increased serotonin (5-HT) levels and downregulated the mRNA expression of 5-HT transporter (SERT) in the hippocampus. The decreased protein expression of growth-associated protein (GAP)-43 induced by CUMS was also ameliorated by resveratrol and fluoxetine. These findings demonstrated the antidepressant effects of resveratrol and suggested that resveratrol was able to promote mitochondrial biogenesis, enhance ATP and 5-HT levels, as well as upregulate GAP-43 expression in the hippocampus.

Landscape of Mitochondria Genome and Clinical Outcomes in Stage 1 Lung Adenocarcinoma.

Risk factors including genetic effects are still being investigated in lung adenocarcinoma (LUAD). Mitochondria play an important role in controlling imperative cellular parameters, and anomalies in mitochondrial function might be crucial for cancer development. The mitochondrial genomic aberrations found in lung adenocarcinoma and their associations with cancer development and progression are not yet clearly characterized. Here, we identified a spectrum of mitochondrial genome mutations in early-stage lung adenocarcinoma and explored their association with prognosis and clinical outcomes. Next-generation sequencing was used to reveal the mitochondrial genomes of tumor and conditionally normal adjacent tissues from 61 Stage 1 LUADs. Mitochondrial somatic mutations and clinical outcomes including relapse-free survival (RFS) were analyzed. Patients with somatic mutations in the D-loop region had longer RFS (adjusted hazard ratio, adjHR = 0.18, p = 0.027), whereas somatic mutations in mitochondrial Complex IV and Complex V genes were associated with shorter RFS (adjHR = 3.69, p = 0.012, and adjHR = 6.63, p = 0.002, respectively). The risk scores derived from mitochondrial somatic mutations were predictive of RFS (adjHR = 9.10, 95%CI: 2.93-28.32, p < 0.001). Our findings demonstrated the vulnerability of the mitochondrial genome to mutations and the potential prediction ability of somatic mutations. This research may contribute to improving molecular guidance for patient treatment in precision medicine.

Depressive-like behaviors are induced by chronic liver injury in male and female mice.

Depression is a highly prevalent mental disease and increasingly become a global public health problem. Recent studies have shown that the dysfunction of liver was associated with depression. However, the previous studies have not been fully explained the relationship between depression and liver injury. The present study was aimed to investigate whether chronic liver injury could induce depressive-like behavior. Chronic liver injury was induced by intraperitoneal injection of carbon (CCl4), D-galactosamine (D-GalN) and thioacetamide (TAA), respectively. And the results showed that the serum activities of ALT in CCl4, D-GalN and TAA groups were significantly increased in both male and female mice compared with the control group, while the activities of AST increased only in CCl4 group. Meanwhile, H&E staining showed that CCl4, D-GalN and TAA induced hepatocytes injury in both male and female mice. Moreover, the sucrose preference was significantly decreased and the immobility time in forced swimming test and tail suspension test were significantly prolonged in CCl4 and D-GalN group compared with control group. Our findings demonstrated that chronic liver injury induced by CCl4 and D-GalN could induce depressive-like behaviors in mice.

Transcriptomic analysis reveals the mechanism of sulfasalazine-induced liver injury in mice.

Liver injury is one of the main toxic effect of sulfasalazine (SASP). However, the toxicological mechanism of SASP-induced liver injury remains unclear. In the present study, the liver injury was induced by orally treatment with SASP for 4 weeks in mice. The hepatic mRNA profiles were detected by RNA sequencing and the differentially expressed genes (DEGs) were analyzed by bioinformatics methods. The elevated serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL), combined with the hepatic histopathological features verified that liver injury was successfully caused by SASP. Transcriptomic results showed that 187 genes (fold change > 1.5 and P < 0.05) were differentially expressed, of which 106 genes were up-regulated and 81 genes were down-regulated in SASP-treated group. Moreover, the further analysis showed that these 187 differentially expressed genes (DEGs) were enriched in 123 GO terms, which mainly including oxidation-reduction process, oxidoreductase activity and epoxygenase P450 pathway. KEGG pathway analysis showed 30 pathways including chemical carcinogenesis, retinol metabolism, arachidonic acid metabolism, linoleic acid metabolism and glutathione metabolism. Among these 187 DEGs, the top 22 hub genes were screened from network of protein-protein interaction (PPI) and verified by qRT-PCR. The results showed that the mRNA levels of hepatic drug-metabolizing enzymes, including cyp2b50, cyp2c50, cyp2c39, cyp2c38, cyp2c29, cyp2c54, cyp2c55, cyp2a5, gsta1, gsta2, gstt2, gstm2 and ephx1, were significantly up-regulated, while egfr and egr1 were down-regulated in SASP-treated group. Moreover, the mRNA levels of egfr and cyp2c55 exhibited a dose-dependent changes in SASP groups. Western blotting verified that the changes of protein levels of EGFR and CYP2C55 were consistent with mRNA levels. Considering that egfr has the highest score in PPI degree and cyp2c55 has the largest fold change in qPCR analysis, our present results suggested that the toxicological mechanisms of SASP-induced liver injury might be related to multi-biological processes and pathways, and egfr and cyp2c55 may play important roles in SASP-induced liver injury. The present study would be helpful for better understanding the hepatotoxic mechanism of SASP. However, the precise mechanism still needs further research.

BLASTP-ACC: Parallel Architecture and Hardware Accelerator Design for BLAST-Based Protein Sequence Alignment.

In this study, we design a hardware accelerator for a widely used sequence alignment algorithm, the basic local alignment search tool for proteins (BLASTP). The architecture of the proposed accelerator consists of five stages: a new systolic-array-based one-hit finding stage, a novel RAM-REG-based two-hit finding stage, a refined ungapped extension stage, a faster gapped extension stage, and a highly efficient parallel sorter. The system is implemented on an Altera Stratix V FPGA with a processing speed of more than 500 giga cell updates per second (GCUPS). It can receive a query sequence, compare it with the sequences in the database, and generate a list sorted in descending order of the similarity scores between the query sequence and the subject sequences. Moreover, it is capable of processing both query and subject protein sequences comprising as many as 8192 amino acid residues in a single pass. Using data from the National Center for Biotechnology Information (NCBI) database, we show that a speed-up of more than 3X can be achieved with our hardware compared to the runtime required by BLASTP software on an 8-thread Intel Xeon CPU with 144 GB DRAM.

Effects of Portulaca Oleracea Extract on Acute Alcoholic Liver Injury of Rats.

The present study was envisaged to investigate the chemical constituents and the intervention effects of Portulaca oleracea extract (POE) on acute alcoholic liver injury of rats. The chemical composition of POE was detected by high performance liquid chromatography (HPLC). Sixty male Wistar rats were divided into 6 groups: Normal control (NC) group, acute alcoholic liver injury model group (ALI), low, medium and high dose of POE (25, 50, 100 mg/kg) groups and bifendate (BF, 3.75 mg/kg) group. Each group was given by intragastrical administration for 7 days. Alcoholic liver injury was induced in the experimental model by administering 50% ethanol at 8 mL/kg and repeated administration after 6 h, for a period of 7 days. The results showed that pretreatment with POE significantly reduced the ethanol-elevated serum level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and triglyceride (TG). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in liver were enhanced followed by administration of POE, while the content of nitric oxide (NO) and malondialdehyde (MDA) was found to decrease. Hepatic content of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was also reduced by POE treatment. These results indicated that POE could increase the antioxidant capacity and relieve the inflammatory injury of the liver cells induced by ethanol. Meanwhile, in our study, POE reduced the expression of miR-122, acetyl coenzyme A carboxylase (ACC) 1 mRNA and protein and increased the expression of lipoprotein lipase (LPL) mRNA and protein in liver, which indicated that POE could improve the lipid metabolism disorder induced by ethanol. Our findings suggested that POE had protective effects on acute alcoholic liver injury of rats.

Tumor mutation burden and recurrent tumors in hereditary lung cancer.

Lung cancer is the leading cause of cancer death worldwide and cancer relapse accounts for the majority of cancer mortality. The mechanism is still unknown, especially in hereditary lung cancer without known actionable mutations. To identify genetic alternations involved in hereditary lung cancer and relapse is urgently needed. We collected genetic materials from a unique hereditary lung cancer patient's blood, first cancer tissue (T1), adjacent normal tissue (N1), relapse cancer tissue (T2), and adjacent normal tissue (N2) for whole genome sequencing. We identified specific mutations in T1 and T2, and attributed them to tumorigenesis and recurrence. These tumor specific variants were enriched in antigen presentation pathway. In addition, a lung adenocarcinoma cohort from the TCGA dataset was used to confirm our findings. Patients with high mutation burdens in tumor specific genes had decreased relapse-free survival (P = 0.017, n = 186). Our study may provide important insight for designing immunotherapeutic treatment for hereditary lung cancer.

Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways.

The present study aimed to evaluate the effects of paeoniflorin on insulin resistance and hepatic steatosis induced by fructose. Male Sprague-Dawley rats were fed 20% fructose drink for eight weeks. The insulin sensitivity, serum lipid profiles, and hepatic lipids contents were measured. The results showed that paeoniflorin significantly decreased serum insulin and glucagon levels, improved insulin sensitivity and serum lipids profiles, and alleviated hepatic steatosis in fructose-fed rats. Moreover, paeoniflorin enhanced the phosphorylation level of AMP-activated protein kinase (AMPK) and protein kinase B (PKB/AKT) and inhibited the phosphorylation of acetyl coenzyme A carboxylase (ACC)1 in liver. Paeoniflorin also increased the hepatic carnitine palmitoyltransferase (CPT)-1 mRNA and protein expression and decreased the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, stearyl coenzyme A decarboxylase (SCD)-1 and fatty acid synthetase (FAS). Furthermore, we found that paeoniflorin significantly increased the heptatic protein expression of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)ß. These results suggest that the protective effects of paeoniflorin might be involved in the activation of LKB1/AMPK and insulin signaling, which resulted in the inhibition of lipogenesis, as well as the activation of ß-oxidation and glycogenesis, thus ameliorated the insulin resistance and hepatic steatosis. The present study may provide evidence for the beneficial effects of paeoniflorin in the treatment of insulin resistance and non-alcoholic fatty liver.

Analysis of clinical characteristics of paroxysmal laryngospasm / 临床耳鼻咽喉头颈外科杂志

OBJECTIVES@#To analyze the clinical characteristics of paroxysmal laryngospasm in adult.@*METHODS@#A retrospective analysis was performed on 149 patients with paroxysmal laryngospasm in adult. All patients underwent the strobolaryngoscopy, completed the reflux symptom index (RSI) or the reflux finding score (RFS). Partial patients underwent an ambulatory 24-hour pH measurement.@*RESULTS@#Laryngospasm was diagnosed in 76 females and 73 males. The average age was 55.4±11.4. The episode time of 149 (98%) patients last from several seconds tominutes, and 139 (93.3%) episodes could have a spontaneous remission. 84 (56.4%) episodes occurred only in the daytime, 28 (18.8%) only in the nighttime. There were 45.6% over weight/obesity patients, including 40 males and 28 females. The smokers were 28.9% (43/149) including 40 males and 3 females, and the drinkers were 29.5% (44/149) with 39 males and 5 females. 76 (51.0%) patients had no induced factor, while some caused by irritable cough/bucking (53,35.6%), cold (15, 10.1%), excitant food/smell (10, 6.7%), or regurgitation (6.5, 4.0%). Strobolaryngoscopy revealed laryngopharyngeal lesions in 46.3% (69/149) patients, including the glottic lesions with 40 (26.8%), unilateral vocal fold paralysis (21, 14.1%) and supraglottic lesions (8,5.4%). RSI/RFS showed 74.5% (111/149) patients had laryngopharyngeal reflux. Two patients treated with dietary and lifestyle modifications get improved, and 15/16 of the patients responded to antireflux treatment.@*CONCLUSIONS@#Episode of paroxysmal laryngospasm occurs more in the daytime, and could have a spontaneous resolution. Paroxysmal laryngospasm is much easier to occur in the male who are overweight or obesity, or with a long-term history of smoking or drinking. Almost half of the patients have an induced factor; partial may have laryngopharyngeal lesions simultaneously. Paroxysmal laryngopharyngeal reflux may be closely related to laryngospasm.

Berberine attenuates depressive-like behaviors by suppressing neuro-inflammation in stressed mice.

Berberine, the major constituent alkaloid originally from the famous Chinese herb Huanglian (Coptis chinensis), has been shown to exert antidepressant-like effects in rodents. However, it is still not clear the involvement of neuro-inflammation suppression in the effects of berberine. The purpose of this study was to determine whether berberine affects the neuro-inflammation system in mice induced by chronic unpredictable mild stress (CUMS). Berberine was orally administrated in normal or CUMS mice for successive four weeks. Behavioral evaluation showed that berberine prevented the depressive deficits both in sucrose preference test and novelty-suppressed feeding test. The elevation of hippocampal pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the activation of microglia were decreased by berberine. In addition, chronic berberine treatment inhibited nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway as the phosphorylated proteins of NF-κB, IκB kinase (IKK)α and IKKß in the hippocampus were suppressed after berberine administration. Furthermore, inducible nitric oxide synthase (iNOS), one downstream target of NF-κB signaling pathway was also inhibited by berberine. In conclusion, these findings suggest that administration of berberine could prevent depressive-like behaviors in CUMS mice by suppressing neuro-inflammation in the hippocampus.

Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3ß and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.