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Clinically, the renin-angiotensin-aldosterone system is activated intensely in patients with moderate to severe traumatic brain injury (TBI). Increased angiotensin II in circulatory blood after TBI can enter the brain through the disrupted blood-brain barrier. Angiotensin-converting enzyme 2 (ACE2) is an enzyme that metabolizes angiotensin II into angiotensin (1-7), which has been shown to have neuroprotective results. The expression and role of ACE2 in the brain after TBI remains elusive, however. We found that ACE2 protein abundance was downregulated around the contusional area in the brains of both humans and mice. Endogenous ACE2 was expressed in neurons, astrocytes, and microglia in the cortex of the mouse brain. Administration of recombinant human ACE2 intracerebroventricularly alleviated neurological defects after TBI in mice. Treatment of recombinant human ACE2 suppressed TBI-induced increase of angiotensin II and the decrease of angiotensin (1-7) in the brain, mitigated neural cell death, reduced the activation of NLRP3 and caspase3, decreased phosphorylation of mitogen-activated protein kinases, and nuclear factor kappa B, and reduced inflammatory cytokines tumor necrosis factor alpha and interleukin-1β. Administration of ACE2 enzyme activator diminazene aceturate intraperitoneally rescued downregulation of ACE2 enzymatic activity and protein abundance in the brain. Diminazene aceturate treatment once per day in the acute stage after TBI alleviated long-term cognitive defects and neuronal loss in mice. Collectively, these results indicated that restoration of ACE2 alleviated neurological deficits after TBI by mitigation of pyroptosis and apoptosis.

The present work aimed at investigating the effects of soy hull polysaccharide (SHP) in alleviating adverse effects in rats fed a high-fat-high-sucrose diet. After SHP feeding for 4 weeks, the fasting blood glucose (FBG), serum triglyceride (TG), serum high-density lipoprotein cholesterol (HDL-C), short chain fatty acids (SCFAs), and 16S rDNA gene sequence were determined. Administration of SHP significantly decreased body fat content and TG levels, and increased water intake and HDL-C levels after 4 weeks of treatment. The antihyperglycemic effect of SHP at a dose of 400 mg/kg mb had the most significant effects among the three dosage groups. SHP notably restored the FBG in rats fed a high-fat-high-sucrose diet (P

Introduction Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. HCC cells possess biological characteristics of high invasion and metastasis. In this respect, to prevent cancer cell invasion and metastasis and early active intervention, we herein screened through the TCGA database for further prognostic analysis including overall survival and disease-free survival . The Kaplan-Meier curve suggested that Cyclin-Dependent Kinase 4 (CDK4) might be an independent prognostic factor for HCC. Moreover, we performed mRNA expression analysis to measure CDK4 levels in normal liver tissues and HCC tissues, and immunohistochemistry analysis to detect protein level of CDK4 in Non-tumor tissue and HCC tissues . Our findings indicated that the expression of CDK4 was significantly higher in tumor tissues compared with Non-tumor tissue in HCC, which increased from HCC stage 1 to 3. Furthermore, the results of transwell-assay indicated that knocking down CDK4 significantly suppresses the invasion and migration of HCC cells, and the results of bioinformatics analysis revealed that genes closely associated with CDK4 are potentially worthy of further investigation. Additionally, the results of Western Blot indicated CDK4 regulates epithelial mesenchymal transition in HCC,and CDK4 appears to regulate EMT and HCC progression via the Wnt/β-catenin pathway. Collectively, this study found the key target gene through bioinformatic analysis and further functional validation through cell experiments. In particular, CDK4 is anticipated to become a crucial hub gene to snipe the metastasis of cancer cells in HCC. Abbreviations: Hepatocellular carcinoma (HCC);Cyclin-Dependent Kinase 4(CDK4);Genomic Data Commons (GDC); genes; EC, Endometrial cancer; GEO, gene expression omnibus; GO, Gene Ontology; GSEA, Gene set enrichment analysis; KEGG, Database; TCGA, The Cancer Genome Atlas; TSGs, tumor suppressor genes;epithelial mesenchymal transition (EMT).

Purpose This article analyzes the image heterogeneity of clear cell renal cell carcinoma (ccRCC) based on positron emission tomography (PET) and positron emission tomography-computed tomography (PET/CT) texture parameters, and provides a new objective quantitative parameter for predicting pathological Fuhrman nuclear grading before surgery. Methods A retrospective analysis was performed on preoperative PET/CT images of 49 patients whose surgical pathology was ccRCC, 27 of whom were low grade (Fuhrman I/II) and 22 of whom were high grade (Fuhrman III/IV). Radiological parameters and standard uptake value (SUV) indicators on PET and computed tomography (CT) images were extracted by using the LIFEx software package. The discriminative ability of each texture parameter was evaluated through receiver operating curve (ROC). Binary logistic regression analysis was used to screen the texture parameters with distinguishing and diagnostic capabilities and whose area under curve (AUC) > 0.5. DeLong's test was used to compare the AUCs of PET texture parameter model and PET/CT texture parameter model with traditional maximum standardized uptake value (SUVmax) model and the ratio of tumor SUVmax to liver SUVmean (SUL)model. In addition, the models with the larger AUCs among the SUV models and texture models were prospectively internally verified. Results In the ROC curve analysis, the AUCs of SUVmax model, SUL model, PET texture parameter model, and PET/CT texture parameter model were 0.803, 0.819, 0.873, and 0.926, respectively. The prediction ability of PET texture parameter model or PET/CT texture parameter model was significantly better than SUVmax model (P = 0.017, P = 0.02), but it was not better than SUL model (P = 0.269, P = 0.053). In the prospective validation cohort, both the SUL model and the PET/CT texture parameter model had good predictive ability, and the AUCs of them were 0.727 and 0.792, respectively. Conclusion PET and PET/CT texture parameter models can improve the prediction ability of ccRCC Fuhrman nuclear grade; SUL model may be the more accurate and easiest way to predict ccRCC Fuhrman nuclear grade. Graphic abstract

Background Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. Results We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. Conclusions This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.

Non-invasive early diagnosis is of great significance in disease pathologic development and subsequent medical treatments, and microRNA (miRNA) detection has attracted critical attention in early cancer screening and diagnosis. High-throughput, sensitive, economic, and fast miRNA sensing platforms are necessary to realize the low-concentration miRNA detection in clinical diagnosis and biological studies. Here, we developed an attomolar-level ultrasensitive, rapid, and multiple-miRNA simultaneous detection platform enabled by nanomaterial locally assembled microfluidic biochips. This platform presents a large linear detection regime of 1 aM-10 nM, an ultralow detection limit of 0.146 aM with no amplification, a short detection time of 35 min with multiplex miRNA sensing capability, and a small sample volume consumption of 2 μL. The detection results of five miRNAs in real samples from breast cancer patients and healthy humans indicate its excellent capacity for practical applications in early cancer diagnosis. The proposed ultrasensitive, rapid, and multiple-miRNA detection microfluidic biochip platform is a universal miRNA detection approach and an important and valuable tool in early cancer screening and diagnosis as well as biological studies.

Objective To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients. Methods A total of 983 gout patients on fenofibrate treatment who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020 were retrospectively enrolled from the electronic records system. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during the treatment period were assessed by a generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr. Results A total of 100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dl within 6 months after fenofibrate initiation. The median change of SCr in the whole cohort was 0.11 mg/dl [interquartile range (IQR) 0.03–0.20], whereas it was 0.36 (0.33–0.45) in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) [odds ratio (OR) 2.39 (95% CI 1.48, 3.86)] and tophus [OR 2.29 (95% CI 1.39, 3.78)] were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily increased, serum urate and triglyceride concentrations decreased using the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, the SCr increase in 65% of patients was reversed after an average of 49 days off the drug. Conclusions This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout needs additional research.

Purposes The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on society and individuals. Based thyroid cancer data from patients treated in Liaocheng People's Hospital from 2015 to 2018, with Chinese national and regional characteristics, in this study, we addressed the controversy of which initial thyroid surgical mode, lobectomy or total thyroidectomy, is most effective. Methods Clinical and pathological data from 2108 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, there were 1001 cases who underwent open operation with total thyroidectomy + central lymph node dissection; meanwhile, 1107 cases were treated with neck lateral lymph node dissection at the same time. Results The overall metastasis rate of all patients was 57.23%. Even the lymph node metastasis of papillary thyroid microcarcinoma (PTMC) was as high as 48.97%. When the mass rose above 2 cm, the proportion of metastasis increased to 77.22%. When the tumor was complicated with bilateral and multiple high‐risk factors, the proportion of metastasis was 65.27% and 72.21%, respectively. When the tumor breaks through the capsule, the metastasis rate was 67.08%. With the increase of tumor diameter, the metastasis of cervical lymph nodes ranged from 22.54% to 73.33%, which showed positive correlation. 49.32% of patients had lymph node metastasis in the lateral cervical region. When the diameter of the tumor reached T1c level, the metastasis of the cervical lymph nodes was 56.91%, and the number of metastatic cases above T1c level accounted for 69.96% of the total metastatic cases. Conclusion The degree of malignancy of thyroid cancer depends on tumor genome evolution. Rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. It is recommended that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life. When the tumor diameter exceeds 1 cm, the risk of cervical lymph node metastasis is high, and we recommended lateral lymph node dissection., There were 1001 cases who underwent open operation with total thyroidectomy + central lymph node dissection, meanwhile 1107 cases were treated with neck lateral lymph node dissection at the same time. It is recommended that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life. When the tumor diameter exceeds 1 cm, the risk of cervical lymph node metastasis is high, and we recommended the lateral lymph node dissection.

ObjectiveTricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.MethodsThis was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients’ data at baseline, before discharge, 30 days and 6 months after the procedure were collected.ResultsAll patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months.ConclusionsThe present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.

Although there has been significant progress in the development of tumor immunotherapies, many challenges still exist for the treatment of solid tumors. Natural killer (NK) cells possess broad-spectrum cytotoxicity against tumors, but their limited migration and infiltration abilities restrict their application in solid tumor therapies. Here, we combined a facile and efficient magnetic-targeting strategy with NK cell-based therapy to develop a novel immunotherapy approach for treating solid tumors. Anti-CD56 antibodies were conjugated with Fe3O4 nanoparticles, which could specifically bind with NK-92 cells endowing them with a magnetic field driven targeting ability. These NK-Fe3O4 biohybrid nanoparticles were able to facilitate directional migration to the tumor site in vivo under external magnetic field guidance and efficiently inhibit tumor growth. These functionalized NK cells represent a novel approach for solid tumor therapy and may provide a promising modality for cancer interventions in the future.

Phloretin, a dihydrochalcone, widely exists in the fruits of apple trees and crabapple trees (Malus prunifolia) with multiple biological activities. Presently, we studied the function of phloretin on the attenuation of hepatic steatosis and further explored the underlying mechanisms both in vitro and in vivo. Male C57BL/6J mice were fed a normal diet or high fat diet (HFD) with or without phloretin (100 mg kg-1) for 12 weeks. HepG2 cells were induced by 200 μM palmitic acid (PA) and co-incubated with phloretin (50 μM) for 24 h. The results showed that phloretin treatment significantly decreased the accumulation of lipids in the liver of the HFD-fed C57BL/6J mice and PA-induced HepG2 cells. Also, phloretin effectively ameliorated hepatic steatosis via promoting fatty acid β-oxidation (FAO). This biological activity of phloretin was closely related to its capacity to improve mitochondrial dysfunction, including the promotion of mitochondrial biosynthesis and inhibition of mitochondrial swelling through the AMPK-dependent SIRT1/PGC-1α and SIRT3/CypD signaling pathways, respectively. These results demonstrate that phloretin effectively improves mitochondrial function and ameliorates HFD-induced hepatic steatosis through an AMPK-dependent signaling pathway.

Objectives: The most common type of noninvasive fungal rhinosinusitis is fungus ball (FB), which usually involves a solitary paranasal sinus. Multiple fungus balls (MFBs) are rarely reported in literature. The purpose of this study was to analyze and compare the clinical features of MFBs and solitary fungus ball (SFB). Methods: We retrospectively investigated consecutive cases of FB between 2001 and 2018 and compared the clinical records of SFB with MFBs with respect to demographics, clinical features, location, radiological findings, and operative outcome. Results: A total of 440 SFB and 43 MFBs cases were included in the study. The mean age was 55.3 ± 13.3 and 60.6 ± 10.9 years, respectively ( P = .011). The incidence of MFBs obviously increased from 2001 to 2018. The clinical symptoms and laboratory examination were similar. On computed tomography images, complete opacification, septal deviation, Haller cells, and obstruction of ostiomeatal complex were more common ( P < .05). The incidence of SFB on the left and right sides was similar, while MFBs were seen to involve both sides in 74.4%. Conclusions: Compared with SFB, MFBs showed some special characteristics. The MFBs affected older patients showed wide range of lesions and complex anatomy. Surgical technique is very important. Much more attention should be paid to this not so uncommon disease during the perioperative period.

BACKGROUND The number of dissected lymph nodes (LNs) in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis. AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy. METHODS We performed a systematic review and searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library from January 1, 2000 until January 1, 2020. Two reviewers examined all the publications independently and extracted the relevant data. Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment (LNs ≥ 12 vs LNs < 12). The primary endpoints were the overall survival (OS) and disease-free survival (DFS). RESULTS Nine articles were included in the meta-analyses. Statistical analysis revealed a statistically significant difference in OS [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.66-0.88, I2 = 12.2%, P = 0.336], DFS (HR = 0.76, 95%CI: 0.63-0.92, I2 = 68.4%, P = 0.013), and distant recurrence (DR) (HR = 0.63, 95%CI: 0.48-0.93, I2 = 30.5%, P = 0.237) between the LNs ≥ 12 and LNs < 12 groups, but local recurrence (HR = 0.67, 95%CI: 0.38-1.16, I2 = 0%, P = 0.348) showed no statistical difference. Moreover, subgroup analysis of LN negative patients revealed a statistically significant difference in DFS (HR = 0.67, 95%CI: 0.52-0.88, I2 = 0%, P = 0.565) between the LNs ≥ 12 and LNs < 12 groups. CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer, our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’ OS, DFS, and DR.

BACKGROUND: Calcification is an important criterion for classification between benign and malignant thyroid nodules. Deep learning provides an important means for automatic calcification recognition, but it is tedious to annotate pixel-level labels for calcifications with various morphologies. OBJECTIVE: This study aims to improve accuracy of calcification recognition and prediction of its location, as well as to reduce the number of pixel-level labels in model training. METHODS: We proposed a collaborative supervision network based on attention gating (CS-AGnet), which was composed of two branches: a segmentation network and a classification network. The reorganized two-stage collaborative semi-supervised model was trained under the supervision of all image-level labels and few pixel-level labels. RESULTS: The results show that although our semi-supervised network used only 30% (289 cases) of pixel-level labels for training, the accuracy of calcification recognition reaches 92.1%, which is very close to 92.9% of deep supervision with 100% (966 cases) pixel-level labels. The CS-AGnet enables to focus the model’s attention on calcification objects. Thus, it achieves higher accuracy than other deep learning methods. CONCLUSIONS: Our collaborative semi-supervised model has a preferable performance in calcification recognition, and it reduces the number of manual annotations of pixel-level labels. Moreover, it may be of great reference for the object recognition of medical dataset with few labels.

Background Biliary cystadenoma (BCA) is a rare benign tumor, accounting for only 5% of reported cystic lesions of the liver. Given its potential for malignancy and high rate of recurrence, surgical resection is the preferred treatment. Therefore, early and accurate preoperative diagnosis is critical to the choice of treatment. We here report the first male case of BCA in our hospital, diagnosed by our team and confirmed by pathological biopsy. This article aims to improve the understanding of this disease and help make a correct diagnosis to better manage it. Case summary A 58-year-old man with irregular abdominal discomfort came to our clinic and was found to have a distended abdomen during physical examination. Computed tomography and magnetic resonance imaging both showed a huge cystic mass in the liver. The patient underwent left hepatic lobectomy, cholecystectomy, and liver cyst fenestration, and most of the masses had decreased in size as of the 6-mo follow-up. The pathological diagnosis was consistent with BCA, and no recurrence was detected after the surgery. BCA occurred mainly in middle-aged women. To the best of our knowledge, this patient is the 11th male case of BCA reported in the literature. Conclusion The combination of magnetic resonance imaging and magnetic resonance cholangiopancreatography is of great significance for the early accurate diagnosis of the disease and the choice of surgical methods.

The purpose of this paper is to study the effect of circRNA cerebellar degeneration-related protein 1 antisense RNA(CDR1as)/miR-671/GSK3β signaling pathway on PC12 cell injury and the mechanism of Exendin-4 (Ex-4) in PC12 cell injury protection. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circular RNA CDR1as and miR-671 in PC12 cells. By overexpressing or knocking out CDR1as, miR-671, and GSK3β, the role of CDR1as, miR-671, and GSK3β in PC12 cell injury was analyzed. The binding of CDR1as to miR-671 and GSK3β to miR-671 was verified by dual luciferase reporter assay. PC12 cells were treated with 1-methyl-4 phenyl-pyridine ion (MPP+) to construct a PC12 cell damage model. PC12 cell transfection experiments were used to confirm the role of CDR1as/miR-671/GSK3β signal axis in PC12 cell damage, and the role of Ex-4 in the association of circRNA CDR1as/miR-671/GSK3β signaling axis and PC12 cell damage. PC12 cell damage was detected by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cellular lactate dehydrogenase (LDH) release. Ex-4 reversed the phosphorylation levels of PI3K, AKT, and GSK-3β in MPP+-treated PC12 cells, and reduced MPP+-induced PC12 cell damage. CircRNA CDR1as upregulated the expression of GSK3β by sponge miR-671. Ex-4 downregulated CDR1as expression and upregulated miR-671 expression in MPP+-induced PC12 cell. Silencing of CDR1as reduced MPP+-induced PC12 cell damage. CDR1as transfection downregulated the expression of miR-671 in PC12 cells, promoted the expression and phosphorylated of GSK3β, and induced PC12 cell damage. GSK3β silencing reversed CDR1as-induced PC12 cell damage. CDR1as promoted the phosphorylation level of GSK3β in PC12 cells to cause cell damage; Ex-4 reversed the phosphorylation of GSK3β caused by CDR1as in PC12 cells and reduced the PC12 cell damage caused by CDR1as. Ex-4 reverses the damage of PC12 cells induced by CDR1as/miR-671/GSK3β signaling pathway.

BACKGROUND: To analyze the risk factors of chronic left ventricular dysfunction (LVD) after cardiac valve surgery. METHODS: A retrospective analysis of 860 patients who underwent heart valve surgery in our center from January 2017 to December 2018, including 650 males and 210 females, aged 58±5.8 years. Inclusion criteria: (I) the patient was clinically diagnosed with heart valve disease and met the surgical indications for mitral valve replacement (MVR), mitral valve repair (MVP), aortic valve replacement (AVR) and double valve replacement (DVR); (II) if atrial fibrillation, coronary artery disease, and tricuspid regurgitation are combined before surgery, radiofrequency ablation, coronary bypass and tricuspid angioplasty were performed contemporarily. Exclusion criteria: (I) preoperative LVEF 55 mm, preoperative LVESD >40 mm, preoperative combined atrial fibrillation, preoperative combined pulmonary hypertension, preoperative NYHA III–IV, and preoperative combined coronary artery disease were the risks of postoperative chronic LVD. CONCLUSIONS: The left ventricular diameter, preoperative coronary artery disease, NYHA III–IV, preoperative atrial fibrillation, and preoperative pulmonary hypertension are risk factors for chronic LVD after heart valve surgery.

Yongkun Wang,1,* Zhen Wu,1,* Yingxue Li,2 Zheng Zheng,2 Jinqiang Yan,2 Shuyan Tian,2 Lin Han2 1Department of Thyroid Surgery, Liaocheng People’s Hospital (Clinical Hospital of Shandong First Medical University) Liaocheng, Shandong, People’s Republic of China; 2Department of Pathology, Liaocheng People’s Hospital (Clinical Hospital of Shandong First Medical University) Liaocheng, Shandong, People’s Republic of China*These authors contributed equally to this work.Correspondence: Lin Han Tel + 86-0635-8273132Email defhme@163.comBackground: Breast cancer is one of the most common cancers worldwide. Long non-coding RNAs and microRNAs act as important regulators in human cancers. This study aims to explore the molecular mechanism among H19, miR-491-5p and zinc finger 703 (ZNF703) in breast cancer.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the expression of H19, miR-491-5p and ZNF703. Cell Counting Kit 8 (CCK-8) assay was performed to evaluate cell proliferation. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells was counted by transwell assay. Dual luciferase reporter assay was carried out to test luciferase activity. Protein level of ZNF703 was measured by Western blot assay.Results: H19 was highly expressed in breast tissues and cells. H19 knockdown inhibited proliferation, induced apoptosis and blocked migration and invasion. Moreover, H19 bound to miR-491-5p and negatively regulated miR-491-5p expression. MiR-491-5p inhibition abrogated the activities of proliferation, apoptosis, migration and invasion affected by H19 knockdown. Furthermore, miR-491-5p directly targeted ZNF703 and inversely modulated ZNF703 expression. ZNF703 up-regulation rescued the effects of miR-491-5p overexpression on proliferation, apoptosis, migration and invasion. In addition, H19 knockdown reduced ZNF703 expression by targeting miR-491-5p/ZNF703 axis.Conclusion: H19 promoted proliferation, migration and invasion and retarded apoptosis of breast cancer cells via sponging miR-491-5p to down-regulate ZNF703 expression.Keywords: breast cancer, H19, miR-491-5p, ZNF703

Objective: Benign paroxysmal positional vertigo (BPPV) has a high recurrence rate, but the risk factor–associated recurrence are elusive. Methods: Searches were performed in PubMed, Embase, Cochrane library, Web of science, Chinese National Knowledge Infrastructure, and Sino Med up to November 3, 2019. The effect size was analyzed by odds ratio and 95% CI. Data from eligible studies were meta-analyzed using Stata version 15.0. Results: Our search resulted in a total of 4076 hits. Twenty-four outcomes of sixty articles were included in the meta-analysis. Risk factors for the recurrence of BPPV included female gender, age (≥65years), hyperlipidemia, diabetes, hypertension, migraine, cervical spondylosis, osteopenia/osteoporosis, head trauma, otitis media, abnormal vestibular evoked myogenic potential, and long use of computers. No significant differences were found in side, type of the involved semicircular canals, smoking, alcohol consumption, stroke, ear surgery, duration of vertigo before treatment, the times of repositioning, Meniere disease, sleep disorders, hypercholesterolemia, and 25-hydroxy vitamin D. Conclusion: These findings strengthen clinical awareness of early warning to identify patients with potential relapse risk of BPPV and clinicians should counsel patients regarding the importance of follow-up after diagnosis of BPPV.

Purpose The incidence of thyroid cancer has increased annually, and has a heavy psychological and economic burden on the society and individuals. Based on thyroid cancer data from patients treated in Liaocheng People's Hospital in 2017, with Chinese national and regional characteristics, in this study we addressed the controversy of which initial thyroid surgical mode, lobectomy, or total thyroidectomy is the most effective. Patients and methods Clinical and pathological data from 552 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, 40 patients underwent endoscopic surgery, with resection, including lobectomy + central lymph node dissection of the affected lobe, while 512 cases underwent total thyroidectomy + central lymph node dissection. Results The metastasis rate for all patients was 59.42%, with lymph node metastasis of papillary thyroid microcarcinoma of 46.92%; however, for patients with tumors >2 cm, the proportion developing metastasis was increased to 77.53%. Conclusion In thyroid cancer, rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. Our data suggest that initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, at least in tumors larger than 1 cm, to avoid the risks associated with secondary surgery and effects on patient quality of life.

OBJECTIVE To elucidate the role of decorin, a small leucine-rich proteoglycan, in the degradation of cartilage matrix during the progression of post-traumatic osteoarthritis (OA). METHODS Three-month-old decorin-null (Dcn-/- ) and inducible decorin-knockout (DcniKO ) mice were subjected to surgical destabilization of the medial meniscus (DMM) to induce post-traumatic OA. The OA phenotype that resulted was evaluated by assessing joint morphology and sulfated glycosaminoglycan (sGAG) staining via histological analysis (n = 6 mice per group), surface collagen fibril nanostructure via scanning electron microscopy (n = 4 mice per group), tissue modulus via atomic force microscopy-nanoindentation (n = 5 or more mice per group) and subchondral bone structure via micro-computed tomography (n = 5 mice per group). Femoral head cartilage explants from wild-type and Dcn-/- mice were stimulated with the inflammatory cytokine interleukin-1β (IL-1β) in vitro (n = 6 mice per group). The resulting chondrocyte response to IL-1β and release of sGAGs were quantified. RESULTS In both Dcn-/- and DcniKO mice, the absence of decorin resulted in accelerated sGAG loss and formation of highly aligned collagen fibrils on the cartilage surface relative to the control (P < 0.05). Also, Dcn-/- mice developed more salient osteophytes, illustrating more severe OA. In cartilage explants treated with IL-1β, loss of decorin did not alter the expression of either anabolic or catabolic genes. However, a greater proportion of sGAGs was released to the media from Dcn-/- mouse explants, in both live and devitalized conditions (P < 0.05). CONCLUSION In post-traumatic OA, decorin delays the loss of fragmented aggrecan and fibrillation of cartilage surface, and thus, plays a protective role in ameliorating cartilage degeneration.

This study aimed to construct a breast ultrasound computer-aided prediction model based on the convolutional neural network (CNN) and investigate its diagnostic efficiency in breast cancer. A retrospective analysis was carried out, including 5000 breast ultrasound images (benign: 2500; malignant: 2500) as the training group. Different prediction models were constructed using CNN (based on InceptionV3, VGG16, ResNet50, and VGG19). Additionally, the constructed prediction models were tested using 1007 images of the test group (benign: 788; malignant: 219). The receiver operating characteristic curves were drawn, and the corresponding areas under the curve (AUCs) were obtained. The model with the highest AUC was selected, and its diagnostic accuracy was compared with that obtained by sonographers who performed and interpreted ultrasonographic examinations using 683 images of the comparison group (benign: 493; malignant: 190). In the model test with the test group images, the AUCs of the constructed InceptionV3, VGG16, ResNet50, and VGG19 models were 0.905, 0.866, 0.851, and 0.847, respectively. The InceptionV3 model showed the largest AUC, with statistically significant differences compared with the other models (P

Introduction Based on thyroid cancer data from patients treated in Liaocheng People's Hospital in 2017, with Chinese national and regional characteristics, in this study we addressed the controversy of which initial thyroid surgical mode, lobectomy or total thyroidectomy, is most effective. Patients and Methods Clinical and pathological data from 552 patients with thyroid cancer, who were initially diagnosed and treated surgically, were collected from the Department of Thyroid Surgery. Among them, 40 patients underwent endoscopic surgery, with resection including lobectomy + central lymph node dissection of the affected lobe, while 512 cases underwent total thyroidectomy + central lymph node dissection. Results The metastasis rate for all patients was 59.42%. Further, among patients with bilateral or multiple tumors or capsule invasion, the proportions who developed metastatic disease were 63.54% and 71.19% and 67.46%, respectively. Meanwhile, the incidence of contralateral accidental malignancy was 7.25% after postoperative paraffin pathology. Discussion Rates of neck lymph node metastasis are high, particularly among patients with risk factors for poor prognosis. It is recommended that, among patients with risk factors, initial treatment should comprise at least total thyroidectomy + central lymph node dissection in China, to avoid the risks associated with secondary surgery and effects on patient quality of life.

Objective To evaluate evidence from published systematic reviews about the effectiveness of exercise interventions on fatigue management in breast cancer patients. Methods PubMed, Web of Science, the Cochrane Library, the Cumulative Index of Nursing and Allied Health (CINAHL), Embase databases, the China National Knowledge Infrastructure (CNKI), the Wanfang database, the China Biomedical Literature Database (CBM), and the VIP database were searched to identify relevant systematic reviews. The reviews which assessed exercise interventions on cancer-related fatigue (CRF) in breast cancer patients were included. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) tool. The Assessment of Multiple Systematic Reviews (AMSTAR) appraisal tool was used to evaluate the methodological quality of included systematic reviews. Results Twenty-four systematic reviews met all the inclusion criteria. The overall mean score for AMSATR is 7.38 and ranged from 4 to 10 points. In addition, 21 reviews arrived at positive conclusions, which exercises could reduce CRF, and 3 obtained that exercise does not affect fatigue. As for GRADE, 8 of the reviews were graded as ‘moderate’, 2 of the studies were ‘very low’, and the others were ‘low’. Conclusions Aerobic and resistance exercise can be regarded as beneficial to CRF in breast cancer patients, and limited evidence exists that yoga had an effect on reducing fatigue. The quality of the current systematic review is still far from satisfactory.

Hereditary spastic paraplegias (HSP) are a group of rare neurodegenerative diseases characterized by progressive spastic paraparesis. UBAP1 was recently found to induce a rare type of HSP (SPG80). We identified a family with eight inherited spastic paraplegic patients carrying a novel heterozygous mutation c.279delG (p.S94Vfs*9) of UBAP1. We demonstrated a lack of functional UBAP1 in these patients, resulting in the neurological disorder caused by interceptions of the ESCRT pathway. Extending from the older onset-age identified from this family, we found that comparing with the European and other populations, Asian patients displayed less proportion of severe patients and an older average age at onset. The origins of SPG80 patients associated with both their onset age and their disease severity, while the age at onset was not correlated with the disease severity.

Ying-Xue Li,1,2 Shan-Shan Ding,3 Wen-Juan Wen,2 Lin Han,2 Hong-Qun Wang,1 Huai-Yin Shi1 1Department of Pathology, Medical School of Chinese People’s Liberation Army, Beijing 100853, People’s Republic of China; 2Department of Pathology, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, People’s Republic of China; 3Department of Pathology, PLA Rocket Force Characteristic Medical Center, Beijing 100032, People’s Republic of ChinaCorrespondence: Huai-Yin ShiDepartment of Pathology, Medical School of Chinese PLA, Beijing 100853, People’s Republic of ChinaTel/fax +86 010 668 873 29Email shy301blk@163.comPurpose: Phosphoinositide 3-kinase (PI3K) and the downstream Akt/mammalian target of rapamycin (mTOR) pathway are central to the control of cell proliferation and survival. Although abnormal activation of this pathway has been well established in a variety of tumours, limited studies are available on synovial sarcoma. The aim of this study was to investigate the expression of several key proteins of those pathways in synovial sarcomas and to correlate the expression of these proteins with clinicopathologic features and prognosis.Patients and Methods: A total of 174 patients with synovial sarcomas were recruited for this study. The phosphorylation status of Akt, mTOR, and eukaryotic translation initiation factor 4E binding protein (4E-BP1) was measured by immunohistochemistry assays in formalin-fixed, paraffin-embedded samples. Correlations between the expression levels of these proteins and clinicopathologic features and prognosis were analysed.Results: The positive rates of phosphorylated (p)Akt, pmTOR, p4E-BP1, and CyclinD1 were 62.7%, 55.6%, 47.1%, and 52.6%, respectively. The positive results of pmTOR, pAkt, and downstream p4E-BP1 were correlated with each other. The positive pAkt, pmTOR, p4E-BP1, and CyclinD1 results were more highly expressed in head and neck and visceral tumours, and positive p4E-BP1 results were correlated with larger size and larger areas of necrosis. In multivariate analysis of clinicopathologic factors, head and neck and visceral location, large tumour size, larger areas of necrosis and frequent mitosis were confirmed as risk factors for shorter overall survival. Positive pAkt, pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival, and CyclinD1 was not in the univariate analysis. The positive pmTOR, pAkt, p4E-BP1, and CyclinD1 results were significantly poor prognostic factors for overall survival, and only positive p4E-BP1 results were significantly associated with shorter event-free survival in multivariate analysis.Conclusion: This study demonstrated the high expression of pAkt, pmTOR, and p4E-BP1 associated with aggressive clinical behaviour in synovial sarcomas and provided evidence for prognostic evaluation and targeted therapy.Keywords: synovial sarcoma, pAkt, pmTOR, p4E-BP1, clinicopathologic features, prognosis

ObjectivesOur objective was to determine the impact of maternal HIV–hepatitis B virus (HBV) coinfection on pregnancy outcomes.MethodsThe current study was conducted in a county of Yi Autonomous Prefecture in southwest China. Data were abstracted from hospitalisation records, including maternal and infant information. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were determined and the impact of maternal HIV–HBV coinfection on adverse pregnancy outcomes was assessed using logistic regression analysis. A treatment effects linear regression model was also applied to examine the effect of HBV, HIV or coinfection to quantify the absolute difference in birth weight from a reference of HBV–HIV negative participants.ResultsA total of 13 198 pregnant women were included in our study, and among them, 99.1% were Yi people and 90.8% lived in rural area. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were 3.6% (95% CI: 3.2% to 3.9%), 3.2% (95% CI: 2.9% to 3.5%) and 0.2% (95% CI: 0.1% to 0.2%) among the pregnant women, respectively. Maternal HIV–HBV coinfection was a risk factor for low birth weight (adjusted OR (aOR)=5.52, 95% CI: 1.97 to 15.40). Compared with the HIV mono-infection group, the risk of low birth weight was significantly higher in the HIV–HBV coinfection group (aOR=3.62, 95% CI: 1.24 to 10.56). Maternal HIV infection was associated with an increased risk of low birth weight (aOR=1.90, 95% CI: 1.38 to 2.60) and preterm delivery (aOR=2.84, 95% CI: 1.81 to 4.47). Perinatal death was more common when mothers were infected with HBV (aOR=2.85, 95% CI: 1.54 to 5.26).ConclusionsThe prevalence of HIV infection was high among pregnant women of the Yi region. Both HIV and HBV infections might have adverse effects on pregnancy outcomes. Maternal HIV–HBV coinfection might be a risk factor for low birth weight in the Yi region, which needs to be confirmed.

Background Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5–10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery. Methods In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis. Results Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3–47.8) vs. 69.0 h (47.8–110.3), p p Conclusions In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.

The present study is undertaken to assess the ability of insoluble dietary fiber (IDF) and soluble dietary fiber (SDF) extracted from soy hulls to relieve colitis in dextran sulfate sodium (DSS) induced inflammatory bowel disease (IBD) in a BALB/C mouse model. We characterized dietary fiber (DF) structures by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Water retention capacity (WRC), water swelling capacity (WSC), oil adsorption capacity (OAC), glucose adsorption capacity (GAC), and the bile acid retardation index (BRI) were measured. The unique surface and chemical structural characteristics endowed DF with good absorption capacity and hydration ability, along with delayed glucose diffusion and absorption of bile acids. IBD was induced with a solution containing 5% DSS in male mice, which were administered a total oral dose of IDF (300 mg kg-1) and SDF (300 mg kg-1) three times per day after successful model establishment. All the mice were assessed weekly for weight change, diarrhea index, and fecal bleeding index. Levels of TLR-4 and NF-κB proteins were measured with western blotting analysis. Cytokine TNF-α in the serum was detected with an enzyme-linked immunosorbent assay (ELISA). Histological methods (H&E) were used to observe part of the mouse colon. The gut microbiota in the colonic contents was analyzed by 16S rRNA gene sequencing. DF decreased weight loss, diarrhea, and fecal bleeding, and also slowed serum TNF-α release. Increases in the levels of NF-κB proteins in inflamed colon tissue were also significantly suppressed by DF treatment. DF ameliorates the colitis induced decrease in gut microbiota species richness. The effect of SDF seemed clearer: the relative abundance of Barnesiella, Lactobacillus, Ruminococcus and Flavonifractor at the genus level was greater than that in the normal control group.

Osteoarthritis (OA) is a whole-joint disease characterized by cartilage destruction, subchondral bone sclerosis, osteophyte formation, and synovitis. However, it remains unclear which part of the joint undergoes initial pathological changes that drives OA onset and progression. In the present study, we investigated the longitudinal alterations of the entire knee joint using a surgically-induced OA mouse model. Histology analysis showed that synovitis occurred as early as 1 week after destabilization of the medial meniscus (DMM), which preceded the events of cartilage degradation, subchondral sclerosis and osteophyte formation. Importantly, key pro-inflammatory cytokines such as IL-1β, IL-6, TNFα, and Ccl2, major matrix degrading enzymes including Adamts4, Mmp3 and Mmp13, as well as nerve growth factor (NGF), all increased significantly in both synovium and articular cartilage. It is notable that the inductions of these factors in synovium are far more extensive than those in articular cartilage. Results from behavioral tests demonstrated that sensitization of knee joint pain developed after 8 weeks, later than histological and molecular changes. In addition, the nanoindentation modulus of the medial tibiae decreased 4 weeks after DMM surgery, simultaneous with histological OA signs, which is also later than appearance of synovitis. Collectively, our data suggested that synovitis precedes and is associated with OA, and thus synovium may be an important target to intervene in OA treatment.

Background: To compare baseline and outcome characteristics of multiple valve surgery with single-valve procedures in a multicenter patient population of mainland China. Methods: From January 2008 to December 2012, data from 14,322 consecutive patients older than 16 years who underwent heart valve surgery at five cardiac surgical centers (except pulmonary valve operations) were collected. The patients were divided into seven subgroups according to the type of valve procedures, and baseline characteristics and postoperative outcomes were contrasted between all seven combinations of single-valve and multiple-valve procedures involving aortic, mitral, and tricuspid valves. Two independent logistic regression analyses were performed and multivariable risk factors for mortality were compared, with emphasis on single-valve versus multiple-valve surgery. Results: Baseline characteristics for MUV procedures (n = 8945) shared many differences to those for single-valve procedures (n = 5377). Proportion of females, chronic obstructive pulmonary disease, cerebrovascular disease, renal impairment, congestive heart failure, NHYA class III-IV, atrial fibrillation, pulmonary hypertension, and decreased ejection fraction were more common in MUV subgroups, and smoker, hypertension, dyslipidemia, active infectious endocarditis, and coronary bypass graft was less frequent. In-hospital mortality was higher for MUV as compared with single-valve procedures (2.4% versus 1.6%, P = .007). Preoperative independent predictors for mortality of patients undergoing MUV procedures were age, chronic obstructive pulmonary disease, diabetes mellitus, renal dysfunction, dialysis, congestive heart failure, cardiogenic shock, NYHA class III-IV, mitral stenosis, tricuspid regurgitation, mitral valve replacement, and concomitant CABG. However, risk factors for mortality were relatively different between single-valve and MUV procedures. Conclusion: Baseline characteristics and epidemiology were different between MUV and single-valve procedures. The in-hospital mortality and postoperative complications for MUV procedures remained considerably higher and determinants of mortality were relatively different across procedures types. These findings serve as a benchmark for further studies, as well as suggest a continued search for explanations of MUV outcomes.

Background: Data on outcome of Stanford type A aortic dissection (TAAD) in Marfan syndrome (MFS) patients are limited. We investigated the full spectrum of reoperation and survival after initial surgery in MFS patients who suffered TAAD. Methods: Retrospective analysis of 85 consecutive MFS patients in one-single center during the past 15 years. Results: Overall, 85 MFS patients with TAAD underwent surgical repair [74% acute dissections; 80% DeBakey type I; 91% composite valved graft; 70% total arch replacement (TAR); 68% frozen elephant trunk (FET); 7% in-hospital mortality] at Changhai hospital affiliated to the Second Military Medical University over the past 15 years. Five (20.8%) patients in non-TAR group need aortic arch reintervention with resternotomy during follow-up, which is significantly higher than that in TAR group (P=0.001). Freedom from aortic arch reoperation in non-TAR group was all 78.7%±8.5% at 5, 10, and 15 years. No patient required aortic arch reoperation in TAR group (P=0.001). On the other hand, the FET was inserted into false lumen intentionally at initial surgery in 2 cases of chronic TAAD with narrowed true lumen. Scheduled thoracoabdominal aortic replacement was performed 6 months later. Both 2 patients are with well clinical outcomes. At last, we found that Debakey type and TAR at initial surgery were irrelevant to survival and reoperation for descending aorta. Conclusions: TAR combined with FET is recommended in MFS patients when the aortic arch is dissected or enlarged. The FET could be inserted into the false lumen intentionally in selective case for scheduled 2-staged descending aortic repair.

Background: The long non-coding RNA (lncRNA)) PCAT6 has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type.Materials and Methods: Wilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach.Results: PCAT6 levels were significantly correlated with CRC patient N stage (OR = 1.8 for N1&N2 vs. N0), lymphatic invasion (OR = 1.9 for Yes vs. No), M stage (OR = 2.1 for M1 vs. M0), CEA level (OR = 1.9 for >5 vs. ≤5), perineural invasion (OR = 1.9 for Yes vs. No), pathologic stage (OR = 1.9 for Stage IIIIV vs. Stage I/II), and neoplasm type (OR = 2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P < 0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P = 0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival (OS) (HR = 1.540; 95% CI: 1.079-2.1997; P = 0.017), with this relationship also being preserved in a multivariate analysis (HR = 6.892; 95% CI: 1.713-27.727, P = 0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2 M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. Conclusions: PCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.

Background Tonsillectomy and tonsillectomy with adenoidectomy are among the most common surgical procedures in otolaryngology practice, but the complications, especially the postoperative bleeding, are seriously troubling surgeons. Some authors had identified that gastroesophageal reflux and LPR are both risk factors for complications in tonsillectomy of children patients. Aims/objectives Therefore, we designed this prospective study to assess the role of LPR in the development of complications following tonsillectomy in adult patients. We want to provide a basis for future clinical practice. Material and methods We recruited a totally of 150 adult patients (18-60 years old) who had an indication of tonsillectomy because of recurrent tonsillitis and divided them into two groups, the laryngopharyngeal reflux (LPR) group and the control group identified by the results of Reflux Symptom Index (RSI) and Reflux Finding Score (RFS). The complications that were observed and evaluated were pain, hemorrhage, fever, infection, and pulmonary problems. Result All the patients complained of pain after surgery. The duration of the pain in the LPR group was much longer than that of the control group. In the LPR group, patients had a similar pain level on the first day after surgery. However, on the 7th day and 14th day after surgery, the pain level was obviously higher than that of the control group. We found that the body temperature mildly rose on the 1st day after surgery and gradually fell to normal level in both groups. No cases had bleeding within 24 h after surgery. There were nine cases of bleeding in the LPR group, while only one case of bleeding occurred in the control group. There were no cases of infection or pulmonary complications in either group. Conclusions and significance LPR is closely related to the complications followed by tonsillectomy and we also suggest that high dosages of proton pump inhibitors (PPI), alkaline water, and alginates should be proscribed to the patients with LPR during the perioperative period.

Essential hypertension (EH) is a clinically frequent cardiovascular disease, with insidious onset, causing increased pressure load and neuroregulation disorders in patients. Long-term EH can cause left ventricular hypertrophy (LVH), which can lead to arrhythmia and even death. The soluble suppression of tumorigenicity 2 (sST2), matrix metalloproteinase-3 (MMP-3), and galectin-3 (Gal-3) in serum plays an important role in the occurrence, development, and prognosis of cardiovascular diseases. In our study, we divided EH patients into 3 levels and groups with or without LVH, according to their condition. The levels of sST2, MMP-3, and Gal-3 in the serum were measured in different groups of patients. Our results showed that the levels of sST2, MMP-3, and Gal-3 in the serum increased progressively with the level in different EH groups. The levels of sST2, MMP-3, and Gal-3 in the serum of the LVH group were higher than those of the NLVH group, and it is positively correlated with LVH-related indexes. The risk of developing and progressing to LVH in patients with EH can be determined by the method of measuring three indicators.

Background psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage. Methods To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored. Results 32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved. Conclusion our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.

Background The Gouqi-wentang formula (GQWTF) is a herbal formula used by Academician Xiao-lin Tong for the clinical treatment of T2DM. GQWTF is beneficial to qi, nourishes Yin, clears heat, and promotes fluid production, but the effective components and their mechanism of action remain unclear. Methods The main components of GQWTF were detected by LC–MS, and the multi-target mechanisms of GQWTF in T2DM were elucidated using network pharmacology analysis, including target prediction, protein–protein interaction network construction and analysis, Gene Ontology (GO) terms, Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway annotation, and other network construction. Finally, the efficacy of the GQWTF was verified using biological experiments. Results First, the “herb-channel tropism” network suggested that GQWTF focuses more on treating diseases by recuperating the liver, which is considered as an important insulin-sensitive organ. Subsequently, a total of 16 active ingredients in GQWTF were detected and screened, and their biological targets were predicted. Then, “compound-target” network was constructed, where enrichment analysis of GQWTF targets reflected its potential pharmacological activities. After T2DM-related target identification, 39 cross targets of GQWTF and T2DM were obtained, and 30 key targets highly responsible for the beneficial effect of GQWTF on T2DM were identified by PPI analysis. GO analysis of these key targets showed that many biological processes of GQWTF in treating T2DM are key in the occurrence and development of T2DM, including components related to inflammatory/immune response, insulin, and metabolism. KEGG analysis revealed the regulation of multiple signalling pathways, such as insulin resistance, PPAR signalling pathway, FoxO signalling pathway, Fc epsilon RI signalling pathway, and pathways that influence diabetes primarily by regulating metabolism as well as other T2DM directly related pathways. Furthermore, a “formula-compound-pathway-symptom” network was constructed to represent a global view of GQWTF in the treatment of T2DM. Conclusions This study explored the mechanism of action of GQWTF in T2DM by multi-component and multi-target multi pathways, which could provide a theoretical basis for the development and clinical application of GQWTF.

Acupuncture has a good effect on improving neurological function after cerebral ischemia‐reperfusion, but there are few studies on the neuroprotective effect of acupuncture from the perspective of ion channel cellular electrophysiology. Studies have shown that the over activation of large‐conductance Ca2+‐activated potassium channel （BKCa） after cerebral ischemia‐reperfusion can reduce the excitability of neurons and induce apoptosis. This study intends to establish middle cerebral artery occlusion/reperfusion (MCAO/R) model, with acupuncture at GV26 as the intervention measure, using patch‐clamp technique to record the electrophysiological changes of BKCa channel. The results showed that the neurological function score of MCAO/R rats was significantly decreased, and the conductance, open dwell time and open probability of BKCa channel in hippocampal CA1 neurons of MCAO/R rats were significantly increased. Acupuncture at GV26 could significantly improve the neurological function scores of MCAO/R rats, and reduce the conductance, open dwell time, and open probability of BKCa channel. The effect of acupuncture at GV26 was significantly better than acupuncture at non‐acupuncture point. The neuroprotective effect of acupuncture at GV26 after cerebral ischemia‐reperfusion may be related to regulating the electrophysiological characteristics of BKCa channel opening., Acupuncture ameliorates neurological function in rats with cerebral ischemia‐reperfusion by regulating the opening of large‐conductance Ca2+‐activated potassium channels

Transient infantile hypertriglyceridemia is a rare autosomal recessive disorder characterized by hypertriglyceridemia, hypohepatia, hepatomegaly, hepatic steatosis and fibrosis in infancy. Mutations in GPD1 gene are considered the causative factor but the underlying mechanism of this disorder is still enigmatic. To date, only 24 different GPD1 mutations have been reported in the literature worldwide with transient infantile hypertriglyceridemia or relevant conditions. Here we report a Chinese girl who developed hepatomegaly hepatic steatosis, elevated transaminase and hypertriglyceridemia from the age of 4 months. A novel homozygous variant c.454C>T (p.Q152*) was found in GPD1 gene by next-generation sequencing. This patient is the 3rd Asian reported with transient infantile hypertriglyceridemia. We summarized the clinical presentations of transient infantile hypertriglyceridemia and also expanded the spectrum of disease-causing mutations in GPD1.

BACKGROUND: Migraine is more common in Meniere’s disease patients, who have some certain anatomical variations. But there are limited studies focusing on the anatomical variations in patients with Meniere’s disease and migraine. OBJECTIVE: To explore the clinical and anatomical features in Meniere’s disease patients with and without migraine, determining whether the coexistence of migraine can be used as a basis for clinical subtyping of Meniere’s disease. METHODS: Ninety-five Meniere’s disease patients and ninety-five healthy subjects matched with age, sex were selected. A detailed questionnaire based on the diagnosis criteria of Meniere’s disease and migraine was designed. According to the CT scan, we divided the mastoid cell system of all the subjects into two types: well-pneumatization type and poor-pneumatization type. Meanwhile, the shortest distance between the sigmoid sinus and the posterior wall of the external acoustic canal was measured. RESULTS: Compared with those without migraine, Meniere‘s disease patients with migraine had a higher female comorbidity, poorer mastoid pneumatization, shorter distance between the sigmoid sinus and posterior wall of the external acoustic canal, longer history, higher frequency of vertigo attacks and better average hearing threshold. CONCLUSIONS: In our study, anatomical features as well as several clinical manifestations were proved to differ significantly between Meniere’s disease patients with and without migraine, indicating the coexistence of migraine may be one standard for the clinical subtyping of Meniere’s disease.

Background: Nursing students who suffer from co-occurring anxiety experience added difficulties when communicating and interacting with others in a healthy, positive, and meaningful way. Previous studies have found strong positive correlations between Internet addiction (IA) and anxiety, suggesting that nursing students who report severe IA are susceptible to debilitating anxiety as well. To date, however, network analysis (NA) studies exploring the nature of association between individual symptoms of IA and anxiety have not been published.Objective: This study examined associations between symptoms of IA and anxiety among nursing students using network analysis.Methods: IA and anxiety symptoms were assessed using the Internet Addiction Test (IAT) and the Generalized Anxiety Disorder Screener (GAD-7), respectively. The structure of IA and anxiety symptoms was characterized using “Strength” as a centrality index in the symptom network. Network stability was tested using a case-dropping bootstrap procedure and a Network Comparison Test (NCT) was conducted to examine whether network characteristics differed on the basis of gender and by region of residence.Results: A total of 1,070 nursing students participated in the study. Network analysis showed that IAT nodes, “Academic decline due to Internet use,” “Depressed/moody/nervous only while being off-line,” “School grades suffer due to Internet use,” and “Others complain about your time spent online” were the most influential symptoms in the IA-anxiety network model. Gender and urban/rural residence did not significantly influence the overall network structure.Conclusion: Several influential individual symptoms including Academic declines due to Internet use, Depressed/moody/nervous only while being off-line, School grades suffering due to Internet use and Others complain about one's time spent online emerged as potential targets for clinical interventions to reduce co-occurring IA and anxiety. Additionally, the overall network structure provides a data-based hypothesis for explaining potential mechanisms that account for comorbid IA and anxiety.

Meniscal tears are associated with a high risk of osteoarthritis but currently have no disease-modifying therapies. Using a Gli1 reporter line, we found that Gli1+ cells contribute to the development of meniscus horns from 2 weeks of age. In adult mice, Gli1+ cells resided at the superficial layer of meniscus and expressed known mesenchymal progenitor markers. In culture, meniscal Gli1+ cells possessed high progenitor activities under the control of Hh signal. Meniscus injury at the anterior horn induced a quick expansion of Gli1-lineage cells. Normally, meniscal tissue healed slowly, leading to cartilage degeneration. Ablation of Gli1+ cells further hindered this repair process. Strikingly, intra-articular injection of Gli1+ meniscal cells or an Hh agonist right after injury accelerated the bridging of the interrupted ends and attenuated signs of osteoarthritis. Taken together, our work identified a novel progenitor population in meniscus and proposes a new treatment for repairing injured meniscus and preventing osteoarthritis.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3,) implicated in ASD and related neurodevelopmental disorders. We identify genotype–phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype–phenotype relationships for ASD by using phenotype-restricted cohorts.

Background Breast cancer has the highest cancer prevalence rate among the women worldwide. Early detection of breast cancer is crucial for successful treatment and reducing cancer mortality rate. However, tumor detection of breast ultrasound (US) image is still a challenging work in computer-aided diagnosis (CAD). Objective This study aims to develop a novel automated algorithm for breast tumor detection based on deep learning. Methods We proposed a new deep learning network named One-step model which have one input and two outputs, the first one was the segmentation result and the other one was used for false-positive reduction. The proposed One-step model includes three key components: Base-net, Seg-net, and Cls-net based on Anchor Box. The model chose DenseNet to construct Base-net, the decoder part of RefineNet as Seg-net, and connected several middle layers of Base-net and Seg-net to Cls-net. From the first output acquired by Base-net and Seg-net, the model detected a series of suspicious lesion regions. Then the second output from the Cls-net was used to recognize and reduce the false-positive regions. Results Experimental results showed that the new model achieved competitive detection result with 90.78% F1 score, which was 8.55% higher than Single Shot MultiBox Detector (SSD) method. In addition, running new model is also computational efficient and has comparative cost effect as SSD. Conclusions We established a novel One-step model which improves location accuracy by generating more precise bounding box via Seg-net and removing false targets by another object detection network (Cls-net). On the other hand, a real-time detection of tumor is achieved by sharing the common Base-net. The experimental results showed that the new model performed well on various irregular and blurred ultrasound images. As a result, this study demonstrated feasibility of applying deep learning scheme to detect breast lesions depicting on US image.

It is predicted that pancreatic ductal adenocarcinoma (PDAC) will become the second most lethal cancer in the US by 2030. PDAC includes a fibrous-like stroma, desmoplasia, encompassing most of the tumor mass, which is produced by cancer-associated fibroblasts (CAFs) and includes their cell-derived extracellular matrices (CDMs). Since elimination of desmoplasia has proven detrimental to patients, CDM reprogramming, as opposed to stromal ablation, is therapeutically desirable. Hence, efforts are being made to harness desmoplasia's anti-tumor functions. We conducted biomechanical manipulations, using variations of pathological and physiological substrates in vitro, to culture patient-harvested CAFs and generate CDMs that restrict PDAC growth and spread. We posited that extrinsic modulation of the environment, via substrate rigidity, influences CAF's cell-intrinsic forces affecting CDM production. Substrates used were polyacrylamide gels of physiological (~1.5 kPa) or pathological (~7 kPa) stiffnesses. Results showed that physiological substrates influenced CAFs to generate CDMs similar to normal/control fibroblasts. We found CDMs to be softer than the corresponding underlying substrates, and CDM fiber anisotropy (i.e., alignment) to be biphasic and informed via substrate-imparted morphological CAF aspect ratios. The biphasic nature of CDM fiber anisotropy was mathematically modeled and proposed a correlation between CAF aspect ratios and CDM alignment; regulated by extrinsic and intrinsic forces to conserve minimal free energy. Biomechanical manipulation of CDMs, generated on physiologically soft substrates, leads to reduction in nuclear translocation of pERK1/2 in KRAS mutated pancreatic cells. ERK2 was found essential for CDM-regulated tumor cell spread. In vitro findings correlated with in vivo observations; nuclear pERK1/2 is significantly high in human PDAC samples. The study suggests that altering underlying substrates enable CAFs to remodel CDMs and restrict pancreatic cancer cell spread in an ERK2 dependent manner.

To compare the functional outcomes between open reduction and internal fixation (ORIF) and closed reduction (CR) for unilateral mandibular extra-capsular condylar fractures in patients over 12 years old.A comprehensive electronic search of PubMed, Embase and the Cochrane Library databases was conducted up to October 31, 2018. The evaluated functional outcomes included malocclusion, temporomandibular joint (TMJ) pain, protrusion, laterotrusion, maximum inter-incisal opening and lateral deviation during maximum inter-incisal opening.Fourteen studies appeared to meet the inclusion criteria. Statistically significant differences between ORIF and CR treatment were observed for the outcomes of malocclusion (P = 0.001), maximum inter-incisal opening (P = 0.0008), lateral deviation during maximum inter-incisal opening (P = 0.007) and laterotrusion (P 0.0001), but not for the outcomes of protrusion (P = 0.33) and TMJ pain (P = 0.29).ORIF treatment of unilateral mandibular extra-capsular condylar fractures provides better functional outcomes in comparison to CR treatment with regard to occlusion, maximum inter-incisal opening, lateral deviation during maximum inter-incisal opening and laterotrusion, whereas there was no statistically significant difference between ORIF and CR group with regard to protrusion and TMJ pain.

Metabolic syndrome (MS), which includes metabolic disorders such as protein disorder, glucose disorder, lipid disorder, and carbohydrate disorder, has been growing rapidly around the world. Glycolipid disorders are a main type of metabolic syndrome and are characterized by abdominal obesity and abnormal metabolic disorders of lipid, glucose, and carbohydrate utilization, which can cause cardiovascular and cerebrovascular diseases. Glycolipid disorders are closely related to intestinal flora and its metabolites. However, studies about the biological mechanisms of the intestinal flora and its metabolites with glycolipid disorders have not been clear. When glycolipid disorders are treated with drugs, a challenging problem is side effects. Traditional Chinese medicine (TCM) and dietary supplements have fewer side effects to treat it. Numerous basic and clinical studies have confirmed that TCM decoctions, Chinese medicine monomers, or compounds can treat glycolipid disorders and reduce the incidence of cardiovascular disease. In this study, we reviewed the relationship between the intestinal flora and its metabolites in glycolipid metabolic disorders and the effect of TCM in treating glycolipid metabolic disorders through the intestinal flora and its metabolites. This review provides new perspectives and strategies for future glycolipid disorders research and treatment.