Thin-Film Buckling Theory and Clinical Application of the Mechanism of Double Eyelid Formation.

BACKGROUND: The mechanism underlying the formation of upper eyelid creases has been the subject of extensive study and ongoing debate. This research aims to elucidate the principles of upper eyelid creases formation, leveraging the membrane bending theory from engineering mechanics. METHODS: We developed an anatomical model of the eyelid and implemented the finite element analysis. Preprocessing and mesh division were conducted using HyperMesh, followed by computational analysis with Abaqus. This approach enabled the observation of dynamic changes in the upper eyelid during eye opening and closing. RESULTS: The study reveals that natural upper eyelid crease formation is influenced by multiple factors. These include the softer texture of the upper eyelid skin and the suborbicularis oculi fat, reduced rigidity at the eyelid crease, optimal contraction force of the upper eyelid, and the strategic placement of the pre-tarsal fat pad just above the eyelid crease. CONCLUSIONS: Ultimately, our findings demonstrate the effectiveness of finite element analysis, grounded in membrane bending theory, in elucidating the dynamics of upper eyelid crease formation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Clinical Characteristics of COVID-19 Patients' Postvaccination.

To investigate the clinical characteristic of domestic coronavirus disease 2019 (COVID-19) patients after vaccination campaign conducted in China. According to vaccination status and months from first vaccine dose to infection detection, patients were divided into unvaccinated, <3 months, 3-6 months, and >6 months groups. The information of demographic and clinical characteristics, laboratory and thoracic computed tomography (CT) findings, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid and IgM, IgG antibodies was retrospectively collected. Therapeutic approaches, temperature-normalizing and viral shedding times, outcomes were also summarized. SARS-CoV-2 antibody levels were further analyzed based on the other following variables: time from second vaccine dose to infection, vaccine dose, the interval from the first to the second dose, and vaccine brand. Among 208 COVID-19 patients, 13 (6.28%) were unvaccinated. No significant differences in demographic and clinical characteristics, laboratory and CT findings, and SARS-CoV-2 nucleic acid loads were detected between groups (all p > 0.05). In comparison with the unvaccinated group, the median SARS-CoV-2 IgG levels were noticeably increased in those vaccinated groups (0.603 in unvaccinated, 15.925 in <3 months, 14.04 in 3-6 months, and 4.94 in >6 months, respectively, p < 0.05). However, SARS-CoV-2 IgG levels were not altered between groups divided based on the other variables. Vaccination does not affect the clinical characteristics in COVID-19 patients. COVID-19 patients with vaccination have high SARS-CoV-2 IgG levels. Underscore the necessity of rapid implementation of vaccination campaigns can be speculated.

Factors affecting recurrent positive RT-PCR results in clinically cured COVID-19 patients: a multicenter study.

The aim of this study was to evaluate factors affecting the recurrence of positive RT-PCR results. By performing a retrospective analysis, we evaluated the clinical data of recurrent positive coronavirus disease 2019 (COVID-19) patients in multiple medical institutions in Wuhan. We recruited COVID-19 patients who were hospitalized from January 1 to March 10, 2020, in three tertiary hospitals in Wuhan, met the discharge criteria and received at least one additional nucleic acid test before leaving the hospital. According to the RT-PCR results, patients were split into a recurrent positive group (RPos group) and a nonrecurrent positive group (non-RPos group). Clinical characteristics, therapeutic schedules and antibody titers were compared between the two groups. AI-assisted chest high-resolution computed tomography (HRCT) technology was applied to investigate pulmonary inflammatory exudation and compare the extent of lung areas with different densities. This study involved 122 COVID-19 patients. There were no significant differences in age, sex, preexisting diseases, clinical symptoms, clinical classification, course of disease, therapeutic schedules or serum-specific antibodies between the two groups. A higher proportion of patients who showed pulmonary inflammatory exudation on HRCT scans were recurrent positive at the time of discharge than other patients (81.6% vs 13.7%, P < 0.01). In addition, the degree of pulmonary fibrosis was higher in the RPos group than in the non-RPos group (P < 0.05). Subpleural exudation at the peripheral edge of the lung and extensive pulmonary fibrosis at the time of discharge represent risk factors for the recurrence of COVID-19.

The Protective Role of the Long Pentraxin PTX3 in Spontaneously Hypertensive Rats with Heart Failure.

Pentraxin 3 (PTX3) is synthesized locally and released into the circulation, reflecting local inflammation in the cardiovascular system. Therefore, we conducted a study to explore the effect of PTX3 in spontaneously hypertensive heart failure (SHHF) rats. Sprague Dawley (SD) and SHHF rats were treated with recombinant PTX3 protein, and the blood pressure (BP) and echocardiographic parameters were collected. Radioimmunoassay, enzyme immunoassay and enzyme-linked immunosorbent assay (ELISA) were applied to detect plasma levels of atrial/B-type natriuretic peptide (ANP/BNP) and PTX3. The pathological changes in the myocardial tissues were observed by hematoxylin and eosin (HE) and Masson stainings. The mRNA and protein expressions were detected by quantitative real-time reverse-transcription polymerase chain reaction (qPCR) and western blotting. Cardiomyocyte apoptosis was evaluated by TUNEL staining and DNA fragmentation test. Increased plasma concentrations of PTX3 were found in SHHF rats compared with SD rats, which was further enhanced by recombinant PTX3 protein. After injection with recombinant PTX3 protein, the heart function was improved in SHHF rats with the decreased systolic and diastolic BP, and the reduced plasma levels of ANP and BNP. Moreover, PTX3 improved the myocardial damage and interstitial fibrosis in SHHF rats with reduced cardiomyocyte apoptosis and decreased mRNA expressions of pro-inflammatory factors in myocardial tissues. PTX3 could decrease the BP and plasma levels of ANP and BNP in SHHF rats, as well as improve the inflammation, cardiomyocyte apoptosis, and pathological changes of myocardial tissues, suggesting it may be a useful intervention in the treatment of SHHF.

Efficacy of tailored second-line therapy of Helicobacter pylori eradication in patients with clarithromycin-based treatment failure: a multicenter prospective study.

BACKGROUND: After the failure of clarithromycin- and bismuth-based quadruple therapy (CBQT), levofloxacin- and bismuth-based quadruple therapy (LBQT) is recommended for Helicobacter pylori eradication. We compared the efficacies of second-line tailored bismuth-based quadruple therapy (TBQT) and empirical LBQT. METHODS: Patients with CBQT failure were randomly assigned to receive TBQT or LBQT for 14 days. All patients underwent endoscopy for culture-based antibiotic susceptibility testing. Patients in the TBQT group exhibiting levofloxacin susceptibility were randomized to receive amoxicillin, levofloxacin, esomeprazole, and colloidal bismuth pectin (ALEB) or amoxicillin, furazolidone, esomeprazole, and colloidal bismuth pectin (AFEB) for 14 days; patients with levofloxacin resistance received AFEB. RESULTS: From May 2016 to June 2019, 364 subjects were enrolled. Eradication rates were significantly higher in the TBQT group (n = 182) than in the LBQT group (n = 182) according to both intention-to-treat (ITT) analysis (89.6% vs. 64.8%, P < 0.001) and per protocol (PP) analysis (91.1% vs. 67.8%, P < 0.001). Among patients in the TBQT group with levofloxacin susceptibility, eradication rates were similar in the ALEB (n = 51) and AFEB (n = 50) subgroups according to both the ITT (86.3% vs. 90.0%, P = 0.56) and PP (88.0% vs. 90.0%, P = 0.75) analyses. Isolated clarithromycin and levofloxacin resistance rates were 57.7% and 44.5%, respectively. The total clarithromycin and levofloxacin resistance rate in strains with dual or triple resistance was 35.7%. CONCLUSIONS: TBQT was more effective than LBQT as a second-line strategy after CBQT failure. In the absence of antibiotic susceptibility testing, AFEB therapy might be used as a rescue therapy to eradicate H. pylori and avoid levofloxacin resistance.Trial registration: Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR1900027743.

An Acute Pulmonary Embolism Patient with Negative D-dimer Masquerading as Right Pneumonia with Pleural Effusion Proven by CT Pulmonary Arteriography: a Case Report and Literature Review.

BACKGROUND: We report an acute pulmonary embolism with negative D-dimer masquerading as right pneumonia with pleural effusion proven by CT pulmonary arteriography (CTPA). METHODS: Appropriate laboratory tests are carried out. The application of vascular ultrasound for the cause of left lower extremity edema. CTPA were performed when vascular ultrasound suggested the existence of venous thrombosis of left lower extremity. RESULTS: Serum D-dimer was negative. Vascular ultrasound revealed left lower extremity venous thrombosis, CTPA demonstrated large emboli in the main pulmonary artery and main pulmonary artery branches. CONCLUSIONS: Negative serum D-dimer is not safe to rule out acute pulmonary embolism. When CT shows peripheral triangle-shaped infiltrate with pleuritis or small pleural exudate, physicians should pay attention to pulmonary infarction.

Evaluation of the real-time fluorescence loop-mediated isothermal amplification assay for the detection of Streptococcus agalactiae.

Streptococcus agalactiae is a major pathogenic bacterium causing perinatal infections in humans. In the present study, a novel real-time fluorescence loop-mediated isothermal amplification technology was successfully developed and evaluated for the detection of S. agalactiae in a single reaction. Six specific primers were designed to amplify the corresponding six regions of fbs B gene of S. agalactiae, using Bst DNA polymerase with DNA strand displacement activity at a constant temperature for 60 min. The presence of S. agalactiae was indicated by the fluorescence in real-time. Amplification of the targeted gene fragment was optimized with the primer 1 in the current setup. Positive result was only obtained for Sa by Real-LAMP among 10 tested relevant bacterial strains, with the detection sensitivity of 300 pg/µl. Real-LAMP was demonstrated to be a simple and rapid detection tool for S. agalactiae with high specificity and stability, which ensures its wide application and broad prospective utilization in clinical practice for the rapid detection of S. agalactiae.

Reliability of three-dimensional color flow Doppler and two-dimensional pulse wave Doppler transthoracic echocardiography for estimating cardiac output after cardiac surgery.

BACKGROUND: Three-dimensional color flow Doppler (3DCF) is a new convenient technique for cardiac output (CO) measurement. However, to date, no one has evaluated the accuracy of 3DCF echocardiography for CO measurement after cardiac surgery. Therefore, this single-center, prospective study was designed to evaluate the reliability of three-dimensional color flow and two-dimensional pulse wave Doppler (2D-PWD) transthoracic echocardiography for estimating cardiac output after cardiac surgery. METHODS: Post-cardiac surgical patients with a good acoustic window and a low dose or no dose of vasoactive drugs (norepinephrine < 0.05 µg/kg/min) were enrolled for CO estimation. Three different methods (third generation FloTrac/Vigileo™ [FT/V] system as the reference method, 3DCF, and 2D-PWD) were used to estimate CO before and after interventions (baseline, after volume expansion, and after a dobutamine test). RESULTS: A total of 20 patients were enrolled in this study, and 59 pairs of CO measurements were collected (one pair was not included because of increasing drainage after the dobutamine test). Pearson's coefficients were 0.260 between the CO-FT/V and CO-PWD measurements and 0.729 between the CO-FT/V and CO-3DCF measurements. Bland-Altman analysis showed the bias between the absolute values of CO-FT/V and CO-PWD measurements was - 0.6 L/min with limits of agreement between - 3.3 L/min and 2.2 L/min, with a percentage error (PE) of 61.3%. The bias between CO-FT/V and CO-3DCF was - 0.14 L/min with limits of agreement between - 1.42 L /min and 1.14 L/min, with a PE of 29.9%. Four-quadrant plot analysis showed the concordance rate between ΔCO-PWD and ΔCO-3FT/V was 93.3%. CONCLUSIONS: In a comparison with the FT/V system, 3DCF transthoracic echocardiography could accurately estimate CO in post-cardiac surgical patients, and the two methods could be considered interchangeable. Although 2D-PWD echocardiography was not as accurate as the 3D technique, its ability to track directional changes was reliable.

MicroRNA-27a mediates the Wnt/ß-catenin pathway to affect the myocardial fibrosis in rats with chronic heart failure.

OBJECTIVE: To clarify the influence of MicroRNA-27a (miR-27a)-mediated Wnt/ß-catenin pathway on the myocardial fibrosis in rats with chronic heart failure (CHF). METHODS: The CHF rat models were constructed and randomly divided into four groups (Sham, Model, AntagomiR-27a, and NC antagomiR-27a groups). Echocardiography was used to test the cardiac function indexes, HE (haematoxylin-eosin) staining to observe the pathological injury of myocardium, Masson staining to analyze the collagen volume fraction (CVF), and qRT-PCR (quantitative real-time PCR) and Western blotting to detect the expressions of miR-27a and Wnt/ß-catenin pathway-related proteins. Besides, cardiomyocytes were isolated and transfected with miR-27a mimic or miR-27a inhibitor to detect the expressions of Wnt/ß-catenin pathway. RESULTS: The CHF rats were significantly increased in LVESD (left ventricular end systolic diameter) and LVEDD (left ventricular end diastolic diameter), and clearly reduced in FS (fractional shortening) and EF (left ventricular ejection fraction) (all P < 0.05). Moreover, LVWI (left ventricular mass index) and CVF (Collagen Volume Fraction), type I and type III collagen, and the ratio of type I/III collagen, as well as the expression of miR-27a, TGF-ß1 and p-Smad2/3, ß-catenin, p-GSK-3ß and α-SMA were also elevated (all P < 0.05). Additionally, the CHF rats treated with AntagomiR-27a were improved in these indexes, and the expression of miR-27a and Wnt/ß-catenin pathway was significantly inhibited (all P < 0.05). Furthermore, cardiomyocytes transfected with miR-27a inhibitor significantly decreased the levels of miR-27a and Wnt/ß-catenin pathway (all P < 0.05). CONCLUSION: Down-regulation of miR-27a may inhibit the Wnt/ß-catenin pathway to reduce the deposition of myocardial collagen, prevent myocardial fibrosis and improve cardiac function. This article is protected by copyright. All rights reserved.

Reversible preoperative renal dysfunction does not add to the risk of postoperative acute kidney injury after cardiac valve surgery.

OBJECTIVE: To evaluate the impact of the renal dysfunction (RD) type and change of postoperative cardiac function on the risk of developing acute kidney injury (AKI) in patients who underwent cardiac valve surgery. METHOD: Reversible renal dysfunction (RRD) was defined as preoperative RD in patients who had not been initially diagnosed with chronic kidney disease (CKD). Cardiac function improvement (CFI) was defined as postoperative left ventricular ejection function - preoperative left ventricular ejection function (ΔEF) >0%, and cardiac function not improved (CFNI) as ΔEF ≤0%. RESULTS: Of the 4,805 (94%) cardiac valve surgery patients, 301 (6%) were RD cases. The AKI incidence in the RRD group (n=252) was significantly lower than in the CKD group (n=49) (36.5% vs 63.3%, P=0.018). The AKI and renal replacement therapy incidences in the CFI group (n=174) were significantly lower than in the CFNI group (n=127) (33.9% vs 50.4%, P=0.004; 6.3% vs 13.4%, P=0.037). After adjustment for age, gender, and other confounding factors, CKD and CKD + CFNI were identified as independent risk factors for AKI in all patients after cardiac valve surgery. Multivariate logistic regression analysis showed that the risk factors for postoperative AKI in preoperative RD patients were age, gender (male), hypertension, diabetes, chronic heart failure, cardiopulmonary bypass time (every 1 min added), and intraoperative hypotension, while CFI after surgery could reduce the risk. CONCLUSION: For cardiac valve surgery patients, preoperative CKD was an independent risk factor for postoperative AKI, but RRD did not add to the risk. Improved postoperative cardiac function can significantly reduce the risk of postoperative AKI.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

Characterization of Antigenic Relatedness between GII.4 and GII.17 Noroviruses by Use of Serum Samples from Norovirus-Infected Patients.

A novel GII.17 norovirus variant caused major gastroenteritis epidemics in China in 2014 to 2016. To explore the host immune factors in selection of the emergence of this new variant, we characterized its antigenic relatedness with the GII.4 noroviruses that have dominated in China for decades. Through an enzyme-linked immunosorbent assay (ELISA) and a histo-blood group antigen (HBGA) blocking assay using sera from GII.4 and the GII.17 variant-infected patients, respectively, we observed limited cross-immune reactivity by the ELISA but little reactivity by the HBGA blocking assay between GII.4 norovirus and the new GII.17 variant. Our data suggest that, among other possible factors, GII.4-specific herd immunity had little role in the emergence of the new GII.17 variant. Thus, GII.17 may be an important active antigenic type or immunotype that needs to be considered for future vaccine strategies against human noroviruses.

Simple and sensitive determination of trace nitrite in water by zero-crossing first-derivative synchronous fluorescence spectrometry using 6-amino-1,3- naphthalenedisulfonic acid as a new fluorescent probe.

A new fluorescent probe, 6-amino-1,3-naphthalenedisulfonic acid (ANDSA), has been developed for the determination of trace nitrite in different waters. This probe is based on the selective reaction of nitrite with ANDSA in hydrochloric acid solution to form the corresponding diazonium acid in sodium hydroxide solution at room temperature. The diazonium acid produced has high fluorescence intensity at 488 nm (excitation at 367 nm), whereas ANDSA has high fluorescence intensity at 465 nm (excitation at 354 nm). The synchronous fluorescence (Δλ = 121 nm) spectrum and the first-derivative synchronous fluorescence spectrum of diazonium acid greatly overlapped with those of ANDSA. The zero-crossing method was used to measure the first-derivative value (dF/dλ) of the first-derivative spectra, in which physical separation of excess ANDSA was unnecessary. The zero-crossing point was located at 351.2 nm for ANDSA, at which dF/dλ of diazonium acid was proportional to the nitrite concentration. Therefore, dF/dλ at 351.2 nm was selected as the analytical signal. Under the optimized experimental conditions, the signal intensity was linear over a nitrite concentration range of 0.006-0.075 mg L-1, with a correlation coefficient better than 0.9994. The limit of detection was 2.1 µg L-1 for the determination of nitrite by the proposed method. The relative standard deviation of the method for the determination of nitrite in real water samples was below 2.45%, and the corresponding recoveries were between 95.7% and 104.1%. The validity of the proposed method was further confirmed by comparison with the reference method with use of the t test. Graphical abstract ANDSA reacts with nitrite to form diazonium acid with higher fluorescence intensity. For ANDSA, dF/dλ was zero at 351.2 nm, whereas dF/dλ of diazonium acid at 351.2 nm was close to the maximum value.

Early Kinetics of Procalcitonin in Predicting Surgical Outcomes in Type A Aortic Dissection Patients.

BACKGROUND: In cardiac surgery, elevation of procalcitonin (PCT) could be observed postoperatively in the absence of any evidence of infection and also seems to be a prognostic marker. PCT levels measured in patients undergoing Type A aortic dissection (TAAD) were used to determine prognostic values for complications and surgical outcomes. METHODS: Measurements of PCT, C-reactive protein (CRP), and leukocyte count were observed in TAAD surgery patients (n = 251; average age: 49.02 ± 12.83 years; 78.5% male) at presurgery (T0) and 24 h (T1), 48 h (T2), and 7 days (T3) postsurgery. PCT clearance (PCTc) on days 2 and 7 was calculated: (PCTday1- PCTday2/day7)/PCTday1 × 100%. Endotracheal intubation duration, length of stay (LOS) in the Intensive Care Unit (ICU)/hospital, and complications were recorded. RESULTS: PCT peaked 24 h postsurgery (median 2.73 ng/ml) before decreasing. Correlation existed between PCT levels at T1 and duration of cardiopulmonary bypass (P = 0.001, r = 0.278). Serum PCT concentrations were significantly higher in nonsurvivor and multiple organ dysfunction syndrome groups on all postoperative days. PCT levels at T1 correlated with length of time of ventilation support and ICU/hospital LOS. Comparing PCT values of survivors versus nonsurvivors, a PCT cutoff level of 5.86 ng/ml at T2 had high sensitivity (70.6%) and specificity (74.3%) in predicting in-hospital death. PCTc-day 2 and 7 were significantly higher in survivor compared with nonsurvivor patients (38% vs. 8%, P= 0.012, 83% vs. -39%, P< 0.001). A PCTc-day 7 cutoff point of 48.7% predicted survival with high sensitivity (77.8%) and specificity (81.8%). CONCLUSIONS: PCT level and PCTc after TAAD surgery might serve as early prognostic markers to predict postoperative outcome. PCT measurement may help identify high-risk patients.

Tunable Pancharatnam-Berry metasurface for dynamical and high-efficiency anomalous reflection.

Pancharatnam-Berry (PB) metasurfaces have intrigued a great deal of interest in recent years for anomalous reflection/refraction, vortex plate, orbital angular momentum, flat lens, photonic spin hall effect (PSHE), holograms and reflect/transmit arrays. However, almost all designs are restricted to fixed electrical performance/functionality once the design is finished. Here, we report for the first time a strategy for PB metasurface with agile working frequency by involving each meta-atom with tunable PIN diodes. For verification, a tunable PB metasurface with frequency reconfigurability is designed and numerically characterized across C and X band. By controlling the external voltages imposed on the diodes, numerical results show that the operation band with 180° phase difference between orthogonal reflection coefficients can be dynamically controlled. As such, the resulting PB metasurface composed of these orderly rotated meta-atoms exhibits a broadband PSHE with nearly 100% conversion efficiency in the "On" state while switches to dual well-separated bands in the "Off" state. Our proposal, not confined to PHSE, set a solid platform for PB phase control and can be populated to any dual-functional and/or multifunctional devices with high integrity, stability and low cost.

Pricing for a basket of LCDS under fuzzy environments.

This paper looks at both the prepayment risks of housing mortgage loan credit default swaps (LCDS) as well as the fuzziness and hesitation of investors as regards prepayments by borrowers. It further discusses the first default pricing of a basket of LCDS in a fuzzy environment by using stochastic analysis and triangular intuition-based fuzzy set theory. Through the 'fuzzification' of the sensitivity coefficient in the prepayment intensity, this paper describes the dynamic features of mortgage housing values using the One-factor copula function and concludes with a formula for 'fuzzy' pricing the first default of a basket of LCDS. Using analog simulation to analyze the sensitivity of hesitation, we derive a model that considers what the LCDS fair premium is in a fuzzy environment, including a pure random environment. In addition, the model also shows that a suitable pricing range will give investors more flexible choices and make the predictions of the model closer to real market values.

The Interaction Between MiR-141 and lncRNA-H19 in Regulating Cell Proliferation and Migration in Gastric Cancer.

BACKGROUND/AIMS: Non-coding RNAs including miRNA and lncRNA had been reported to regulate gene expression and were both related to cancer progression. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition (EMT) process and H19 has also been demonstrated to promote malignancy in various cancers. We aimed to determine the correlation between miR-141 and H19 and their roles in gastric cancer in this study. METHODS: H19 and miR-141 expression were detected by qRT-PCR. By bioinformatic analysis and luciferase assay we examined the correlation between H19 and miR-141 in vitro. RESULTS: H19 expression was found to be inversely correlated to miR-141 expression in gastric cancer cells and tissues. H19 promotes malignancy including proliferation and invasion whereas miR-141 suppresses malignancy in human cancer cells. MiR-141 binds to H19 in a sequence specific manner, and suppresses H19 expression and functions including proliferation and invasion. MiR-141 could also regulate H19 target genes and miR-141 inhibitor restores H19 siRNA function, while H19 regulates miR-141 target gene ZEB1. CONCLUSION: These results were the first to demonstrate that H19 and miR-141 could compete with each other and affect their target genes in gastric cancer, which provide important clues for understanding the key roles of lncRNA-miRNA functional network in cancer.

ShRNA-mediated silencing of the ubiquitin-specific protease 22 gene restrained cell progression and affected the Akt pathway in nasopharyngeal carcinoma.

Ubiquitin-specific protease 22 (USP22) is closely related with poor prognosis of cancer patients. However, the role of USP22 expression in nasopharyngeal carcinoma (NPC) has not been determined. The main aim of this study was to determine the role of USP22 in the pathologic processes of NPC. Immunohistochemistry (IHC), western blot (WB), and real-time polymerase chain reaction (RT-PCR) were used to measure the expression of USP22 in cell lines and tissues of NPC in comparison with expression in non-cancerous cells and tissues. USP22-specific short hairpin RNA (shRNA) was used to knock down USP22 expression in the NPC cell line CNE-1 and CNE-2. Furthermore, the impact of USP22 in cellular proliferation, growth, and cell cycle were detected respectively. WB was used to determine the role of USP22 in the AKT/GSK-3/Cyclin signaling pathway. The expression levels of USP22 were remarkably higher in NPC cell lines and tissues. With cell counting and the MTS assay, cellular growth and proliferation progression of USP22 knockdown cell line was shown to be effectively restrained. The USP22 silencing both in CNE-1 and CNE-2 cells caused them to accumulate in the G0/G1 phase of the cell cycle. USP22 knockdown was also found to modulate the AKT/GSK-3/Cyclin pathway, resulting in downregulation of p-AKT, p-GSK-3ß, and cyclinD1. This study suggests that USP22 plays a critical regulatory role in the pathologic processes of NPC, and that it may be a potential biological treatment target in the future.

EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated sonic hedgehog.

Misfolded proteins of the endoplasmic reticulum (ER) are eliminated by the ER-associated degradation (ERAD) in eukaryotes. In S. cerevisiae, ER-resident lectins mediate substrate recognition through bipartite signals consisting of an unfolded local structure and the adjacent glycan. Trimming of the glycan is essential for the directional delivery of the substrates. Whether a similar recognition and delivery mechanism exists in mammalian cells is unknown. In this study, we systematically study the function and substrate specificity of known mammalian ER lectins, including EDEM1/2/3, OS-9 and XTP-3B using the recently identified ERAD substrate sonic hedgehog (SHH), a soluble protein carrying a single N-glycan, as well as its nonglycosylated mutant N278A. Efficient ERAD of N278A requires the core processing complex of HRD1, SEL1L and p97, similar to the glycosylated SHH. While EDEM2 was required for ERAD of both glycosylated and non-glycosylated SHHs, EDEM3 was only necessary for glycosylated SHH and EDEM1 was dispensable for both. Degradation of SHH and N278A also required OS-9, but not the related lectin XTP3-B. Robust interaction of both EDEM2 and OS-9 with a non-glycosylated SHH variant indicates that the misfolded polypeptide backbone, rather than a glycan signature, functions as the predominant signal for recognition for ERAD. Notably, SHH-N278A is the first nonglycosylated substrate to require EDEM2 for recognition and targeting for ERAD. EDEM2 also interacts with calnexin and SEL1L, suggesting a potential avenue by which misfolded glycoproteins may be shunted towards SEL1L and ERAD rather than being released into the secretory pathway. Thus, ER lectins participate in the recognition and delivery of misfolded ER substrates differently in mammals, with an underlying mechanism distinct from that of S. cerevisiae.