Insect cells of Spodoptera frugiperda support WSSV gene replication but not progeny virion assembly.

The lacking of stable and susceptible cell lines has hampered research on pathogenic mechanism of crustacean white spot syndrome virus (WSSV). To look for the suitable cell line which can sustain WSSV infection, we performed the studies on WSSV infection in the Spodoptera frugiperda (Sf9) insect cells. In consistent with our previous study in vitro in crayfish hematopoietic tissue cells, the WSSV envelope was detached from nucleocapsid around 2 hpi in Sf9 cells, which was accompanied with the cytoplasmic transport of nucleocapsid toward the cell nucleus within 3 hpi. Furthermore, the expression profile of both gene and protein of WSSV was determined in Sf9 cells after viral infection, in which a viral immediate early gene IE1 and an envelope protein VP28 exhibited gradually increased presence from 3 to 24 hpi. Similarly, the significant increase of WSSV genome replication was found at 3-48 hpi in Sf9 cells after infection with WSSV, indicating that Sf9 cells supported WSSV genome replication. Unfortunately, no assembled progeny virion was observed at 24 and 48 hpi in Sf9 cell nuclei as determined by transmission electron microscope, suggesting that WSSV progeny could not be assembled in Sf9 cell line as the viral structural proteins could not be transported into cell nuclei. Collectively, these findings provide a cell model for comparative analysis of WSSV infection mechanism with crustacean cells.

Targeted modulation of gut microbiota by traditional Chinese medicine and natural products for liver disease therapy.

The gut microbiota not only constitutes intestinal microenvironment homeostasis and human health but also exerts indispensable roles in the occurrence and progression of multiple liver diseases, including alcohol-related liver disease, nonalcoholic fatty liver disease, autoimmune liver disease and liver cancer. Given the therapeutic status of these diseases, their prevention and early therapy are crucial, and the detailed mechanism of gut microbiota in liver disease urgently needs to be explored. Meanwhile, multiple studies have shown that various traditional Chinese medicines, such as Si Miao Formula, Jiangzhi Granules, Liushen Capsules, Chaihu-Shugan Power, Cassiae Semen and Gynostemma, as well as some natural products, including Costunolide, Coprinus comatus polysaccharide, Antarctic krill oil, Oridonin and Berberine, can repair liver injury, improve fatty liver, regulate liver immunity, and even inhibit liver cancer through multiple targets, links, and pathways. Intriguingly, the aforementioned effects demonstrated by these traditional Chinese medicines and natural products have been shown to be closely related to the gut microbiota, directly driving the strategy of traditional Chinese medicines and natural products to regulate the gut microbiota as one of the breakthroughs in the treatment of liver diseases. Based on this, this review comprehensively summarizes and discusses the characteristics, functions and potential mechanisms of these medicines targeting gut microbiota during liver disease treatment. Research on the potential effects on gut microbiota and the regulatory mechanisms of traditional Chinese medicine and natural products provides novel insights and significant references for developing liver disease treatment strategies. In parallel, such explorations will enhance the comprehension of traditional Chinese medicine and natural products modulating gut microbiota during disease treatment, thus facilitating their clinical investigation and application.

Pseudomonas aeruginosa Induces Interferon-ß Production to Promote Intracellular Survival.

Pseudomonas aeruginosa (PA) is known as one kind of extracellular pathogens. However, more evidence showed that PA encounters the intracellular environment in different mammalian cell types. Little is known of innate immune factors modulating intracellular PA survival. In the present study, we proposed that interferon-ß (IFN-ß) is beneficial to the survival of PA in the cytoplasm of macrophages. Furthermore, we found that interleukin-1ß (IL-1ß) induced by PA suppresses IFN-ß response driven by the cGAS-STING-TBK1 pathway. Mechanistically, IL-1ß decreased the production of cyclic GMP-AMP (cGAMP) by activating AKT kinase. cGAMP is necessarily sufficient to stimulate the transcription of IFN-ß via the STING adaptor-TBK1 kinase-IRF3 transcription factor axis. Thus, our findings uncovered a novel module for PA intracellular survival involving IFN-ß production restricted by IL-1ß and provided a strong rationale for a potential clinical strategy against pulmonary PA infection patients. IMPORTANCE The link between innate immunity and intracellular Pseudomonas aeruginosa is unclear. Our studies illuminated the role of interferon-ß (IFN-ß) in remote intracellular PA infection. Furthermore, our experimental evidence also indicated that IL-1ß is a negative regulator of IFN-ß production and, in particular, P. aeruginosa infection. The inhibition of IFN-ß may be used as a potential therapeutic method against pulmonary PA infection.

Airway acidification impaired host defense against Pseudomonas aeruginosa infection by promoting type 1 interferon ß response.

Airway microenvironment played an important role in the progression of chronic respiratory disease. Here we showed that standardized pondus hydrogenii (pH) of exhaled breath condensate (EBC) of bronchiectasis patients was significantly lower than that of controls and was significantly correlated with bronchiectasis severity index (BSI) scores and disease prognosis. EBC pH was lower in severe patients than that in mild and moderate patients. Besides, acidic microenvironment deteriorated Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection in mice models. Mechanistically, acidic microenvironment increased P. aeruginosa outer membrane vesicles (PA_OMVs) released and boosted it induced the activation of interferon regulatory factor3 (IRF3)-interferonß (IFN-ß) signalling pathway, ultimately compromised the anti-bacteria immunity. Targeted knockout of IRF3 or type 1 interferon receptor (IFNAR1) alleviated lung damage and lethality of mice after P. aeruginosa infection that aggravated by acidic microenvironment. Together, these findings identified airway acidification impaired host resistance to P. aeruginosa infection by enhancing it induced the activation of IRF3-IFN-ß signalling pathway. Standardized EBC pH may be a useful biomarker of disease severity and a potential therapeutic target for the refractory P. aeruginosa infection. The study also provided one more reference parameter for drug selection and new drug discovery for bronchiectasis.

Invasion and Propagation of White Spot Syndrome Virus: Hijacking of the Cytoskeleton, Intracellular Transport Machinery, and Nuclear Import Transporters.

The pathogenesis of white spot syndrome virus (WSSV) is largely unclear. In this study, we found that actin nucleation and clathrin-mediated endocytosis were recruited for internalization of WSSV into crayfish hematopoietic tissue (Hpt) cells. This internalization was followed by intracellular transport of the invading virions via endocytic vesicles and endosomes. After envelope fusion within endosomes, the penetrated nucleocapsids were transported along microtubules toward the periphery of the nuclear pores. Furthermore, the nuclear transporter CqImportin α1/ß1, via binding of ARM repeat domain within CqImportin α1 to the nuclear localization sequences (NLSs) of viral cargoes and binding of CqImportin ß1 to the nucleoporins CqNup35/62 with the action of CqRan for docking to nuclear pores, was hijacked for both targeting of the incoming nucleocapsids toward the nuclear pores and import of the expressed viral structural proteins containing NLS into the cell nucleus. Intriguingly, dysfunction of CqImportin α1/ß1 resulted in significant accumulation of incoming nucleocapsids on the periphery of the Hpt cell nucleus, leading to substantially decreased introduction of the viral genome into the nucleus and remarkably reduced nuclear import of expressed viral structural proteins with NLS; both of these effects were accompanied by significantly inhibited viral propagation. Accordingly, the survival rate of crayfish post-WSSV challenge was significantly increased after dysfunction of CqImportin α1/ß1, also showing significantly reduced viral propagation, and was induced either by gene silencing or by pharmacological blockade via dietary administration of ivermectin per os. Collectively, our findings improve our understanding of WSSV pathogenesis and support future antiviral designing against WSSV. IMPORTANCE As one of the largest animal DNA viruses, white spot syndrome virus (WSSV) has been causing severe economical loss in aquaculture due to the limited knowledge on WSSV pathogenesis for an antiviral strategy. We demonstrate that the actin cytoskeleton, endocytic vesicles, endosomes, and microtubules are hijacked for WSSV invasion; importantly, the nuclear transporter CqImportin α1/ß1 together with CqRan were recruited, via binding of CqImportin ß1 to the nucleoporins CqNup35/62, for both the nuclear pore targeting of the incoming nucleocapsids and the nuclear import of expressed viral structural proteins containing the nuclear localization sequences (NLSs). This is the first report that NLSs from both viral structure proteins and host factor are elaborately recruited together to facilitate WSSV infection. Our findings provide a novel explanation for WSSV pathogenesis involving systemic hijacking of host factors, which can be used for antiviral targeting against WSSV disease, such as the blockade of CqImportin α1/ß1 with ivermectin.

Clinical significance of long noncoding RNA MNX1-AS1 in human cancers: a meta-analysis of cohort studies and bioinformatics analysis based on TCGA datasets.

MNX1-AS1 expression has been proposed to be abnormally upregulated in multiple human malignancies and be linked with the survival outcome of patients. However, relevant conclusions were yielded based on the limited samples. Therefore, we herein implemented a meta-analysis of the published cohort studies to further decipher the relationship of MNX1-AS1 level to prognosis and clinicopathological features in various cancers. Additionally, using The Cancer Genome Atlas (TCGA) datasets we carried out a bioinformatics analysis to make a further evaluation on the prognostic value of MNX1-AS1 expression. The results of meta-analysis indicated elevated MNX1-AS1 level closely correlated with poorer overall survival (OS) (HR = 1.97, 95% CI, 1.73-2.24; P < 0.00001), and disease-free survival (DFS) (HR = 2.24, 95% CI, 1.48-3.38; P = 0.0001) in cancers, which was confirmed by the bioinformatics analysis. Besides, it was observed the upregulated MNX1-AS1 level was significantly related to invasion depth, disease stage, tumor metastasis, and differentiation. Collectively, high MNX1-AS1 level correlated with poor survival outcome and aggressive clinicopathological characteristics in various cancers, suggesting that MNX1-AS1 may be applied as a prognostic marker and even a therapeutic target. Nevertheless, more high-quality studies designed with a large sample size should be conducted to further determine the clinical role of MNX1-AS1 in specific cancer types.

Prognostic Value of Combination of Inflammatory and Tumor Markers in Resectable Gastric Cancer.

BACKGROUND: Inflammatory response and tumor marker levels have been shown to correlate with the prognosis in several human tumors. However, only a few studies on these markers have been performed in gastric cancer (GC) patients; the clinical significance of the combined markers is unclear. We aimed to evaluate the role of the combination of preoperative neutrophil-to-lymphocyte ratio (NLR) and carbohydrate antigen 19-9 (CA19-9) for predicting the prognosis of patients with GC. METHODS: This retrospective study included 458 patients who underwent gastrectomy with curative intent between January 2013 and July 2014 in the second hospital of Lanzhou University. Receiver operating characteristic curve (ROC) was performed to determine the cut-off values for biomarkers, and their prognostic values were assessed using the Kaplan-Meier curve. The combined score indicators were established based on the optimal cut-off values, which range from 0 to 2. Prognostic significances for overall survival (OS) were assessed by univariate and multivariate Cox regression analysis. Nomogram was used as a visual supplement for the prognostic score system, and the predictive accuracy and discriminative ability were determined by the concordance index (C-index) and calibration curve. RESULTS: The Kaplan-Meier survival analysis showed that the 1-, 3-, and 5-year OS were 66.2% (n = 303), 42.8% (n = 196), and 40.2% (n = 184) in all 458 patients, respectively. The high NLR (≥1.96), PLR (≥126), CA19-9 (≥27 U/mL), and CEA (≥ 5 ng/mL) were associated with poor prognosis of GC patients. The NLR + CA19-9 score indicator proved to be related to tumor size, lymph node metastasis, vascular invasion, perineural invasion, T stage, N stage, TNM stage, PLR, and CEA in patients with GC and an independent prognostic factor for prediction of 5-year OS (score 1: HR = 1.423, 95%CI: 1.049-1.929, P = 0.023; score 2: HR = 2.740, 95%CI: 1.882-3.990, P < 0.001). NLR + CA19-9 has a better predictive ability than other combined or single score indicators based on inflammation and tumor markers (AUC = 0.662, 95%CI: 0.616-0.705, P < 0.001). Moreover, a nomogram was established by the significant characteristics in the multivariate analysis for OS, which represented high accuracy (C-index = 0.692, 95%CI: 0.675-0.708). CONCLUSION: NLR + CA19-9 can independently predict the overall survival of patients with gastric cancer after surgery. The prognostic nomogram based on NLR + CA19-9 is a convenient, economical, and effective prognostic system for clinical practice.

A Reverse Orbicularis-Tarsus Fixation Technique in Double-Eyelid Blepharoplasty: A Novel Fixation Technique Different From Park's Technique.

BACKGROUND: Although Park's "orbicularis-levator fixation technique" has been widely used as a mature double-eyelid surgery in China recently. Shortcomings related to this method cannot be ignored. Thus, a reverse orbicularis-tarsus fixation technique in double-eyelid blepharoplasty has now been devised. The method is to create a physiological double-eyelid fold based on the formation mechanism of double-eyelid creases. METHODS: A retrospective study of 112 Chinese patients who underwent double-eyelid surgery between October 2017 and September 2019 was undertaken through a review of medical records. All these patients underwent a reverse tarsus and orbicularis oculi muscle fixation technique, with postoperative follow-up ranging from 6 months to 2 years. Postoperative outcomes were reviewed, evaluated, and analyzed. RESULTS: Altogether, 112 patients who underwent the double-eyelid surgery were reviewed. Among them, the results were judged as excellent in 104 cases (92.9%), good in 4 cases (3.6%), fair in 3 cases (2.7%), and poor in 1 case (0.8%). Clinical effectiveness was satisfactory in most of the patients (104/112, 92.9%). Only 5 patients (4.5%) expressed subjective dissatisfaction with postoperative outcomes; of these, 3 patients complained of eyelids asymmetry (2.7%). Two patients complained of eyelids scar formation (1.7%); Whereas surgical revision was required in only 1 patient (0.8%). CONCLUSIONS: The reverse orbicularis-tarsus fixation technique for upper eyelid blepharoplasty is safe and effective, with better biomechanics and a satisfying aesthetic outcome. Therefore, this provides an alternative option in Chinese double-eyelid surgery.Level of Evidence: Level IV, case studies.

Recent insights into hematopoiesis in crustaceans.

Hematopoiesis refers to the phenomenon that hematopoietic stem cells (HSCs) continuously form and produce blood cells with multiple functions. In crustacean, the hematopoietic process produces a variety of hemocytes that form the core and basis of cellular and humoral immunity, which is crucial for crustacean to maintain their lives and protect themselves against microbial infection. The expression of many factors, in the form of transcription factors and humoral factors, are altered during hematopoiesis, which are involved in the regulation of hematopoiesis. Meanwhile, there are also factors that, although not directly involved in the HSCs differentiation or hemocytes production and release, play an essential role in maintaining cellular homeostasis. In this review, we summarize current knowledge on the hematopoietic lineage of crustacean, with a particular focus on the molecular regulation of hematopoiesis, including transcriptional regulation, humoral factors involved in the differentiation of HSCs and the maintenance of hematopoietic homeostasis, which contributes to a systematic understanding of the crustacean hematopoiesis.

CqPP2A inhibits white spot syndrome virus infection by up-regulating antimicrobial substances expression in red claw crayfish Cherax quadricarinatus.

Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase, a highly conserved enzyme widely expressed in eukaryotic cells, which accounts for a majority of the serine/threonine phosphatase activity in cells implicated in regulation of immune signaling pathways and antiviral response. However, most of studies about PP2A have been conducted in mammals but few in crustaceans. In this study, two subunits of PP2A (named as CqPP2Ab and CqPP2Ac) were characterized to be involved in white spot syndrome virus (WSSV) infection in the haematopoietic tissue (Hpt) cells from red claw crayfish Cherax quadricarinatus. The open reading frame (ORF) of CqPP2Ab was 1341 bp encoding 446 amino acids with seven WD40 domains, and the ORF of CqPP2Ac was 930 bp encoding 309 amino acids with a PP2Ac domain. Tissue distribution analysis showed that the mRNA transcript of CqPP2Ab and CqPP2Ac were both widely expressed in all the tested tissues with the highest expression in hemocyte, followed by high expression in Hpt. The gene expressions of CqPP2Ab and CqPP2Ac were both significantly down-regulated at 6 h post WSSV infection (6 hpi) in Hpt cells. Importantly, the expression of viral immediate early gene IE1 and late viral gene envelope protein VP28 were both significantly increased post WSSV infection after gene silencing of CqPP2Ab or CqPP2Ac in Hpt cells, suggesting that CqPP2Ab and CqPP2Ac could inhibit WSSV infection in Hpt cells, probably by increasing the antimicrobial substances expression in consideration to the significantly reduced expression of anti-lipopolysaccharide factor, crustin, and lysozyme after gene silencing of CqPP2Ab or CqPP2Ac, respectively. These findings provide a new light on the mechanism of WSSV infection and the antiviral response in crustaceans.

Role of Orbicular Oculi Muscle Resection in Double Eyelid Surgery to Correct Ptosis of Young Adults: A Retrospective Review in 121 Chinese Patients.

BACKGROUND: A plump single eyelid with ptosis is the morphological feature of Asians. Orbicularis oculi muscle (OOM) technique can correct ptosis and get a good appearance. METHODS: A retrospective study was conducted in 121 Chinese patients who underwent double eyelid surgery with medial epicanthoplasty using OOM resection technique from December 2016 to December 2019. Preoperatively, all the patients had good or excellent levator function while skin fold overlapping the upper eyelid margin was found. Palpebral fissure height, upper eyelid margin reflex distance, complications, and cosmetic results were evaluated. Comparisons were performed preoperatively and postoperatively. RESULTS: The study included 121 patients. Mean follow-up time was 12.8 months (range, 6-32 months). Mean margin reflex distance increased from 1.96 ± 0.60 mm preoperatively to 3.74 ± 0.50 mm postoperatively (P < 0.001), mean palpebral fissure height increased from 6.31 ± 0.51 mm preoperatively to 8.33 ± 0.52 mm postoperatively (P < 0.001). Most patients obtained satisfactory results. Only 1 patient was under correction, 2 patients were with mild asymmetry 6 months postoperatively. CONCLUSIONS: Ptosis of the upper eyelid can be corrected by the OOM resection technique without any procedure on levator muscle. This technique can be an alternative method for the correction of ptosis of the upper eyelid.

White Spot Syndrome Virus Benefits from Endosomal Trafficking, Substantially Facilitated by a Valosin-Containing Protein, To Escape Autophagic Elimination and Propagate in the Crustacean Cherax quadricarinatus.

As the most severely lethal viral pathogen for crustaceans in both brackish water and freshwater, white spot syndrome virus (WSSV) has a mechanism of infection that remains largely unknown, which profoundly limits the control of WSSV disease. By using a hematopoietic tissue (Hpt) stem cell culture from the red claw crayfish Cherax quadricarinatus suitable for WSSV propagation in vitro, the intracellular trafficking of live WSSV, in which the acidic-pH-dependent endosomal environment was a prerequisite for WSSV fusion, was determined for the first time via live-cell imaging. When the acidic pH within the endosome was alkalized by chemicals, the intracellular WSSV virions were detained in dysfunctional endosomes, resulting in appreciable blocking of the viral infection. Furthermore, disrupted valosin-containing protein (C. quadricarinatus VCP [CqVCP]) activity resulted in considerable aggregation of endocytic WSSV virions in the disordered endosomes, which subsequently recruited autophagosomes, likely by binding to CqGABARAP via CqVCP, to eliminate the aggregated virions within the dysfunctional endosomes. Importantly, both autophagic sorting and the degradation of intracellular WSSV virions were clearly enhanced in Hpt cells with increased autophagic activity, demonstrating that autophagy played a defensive role against WSSV infection. Intriguingly, most of the endocytic WSSV virions were directed to the endosomal delivery system facilitated by CqVCP activity so that they avoided autophagy degradation and successfully delivered the viral genome into Hpt cell nuclei, which was followed by the propagation of progeny virions. These findings will benefit anti-WSSV target design against the most severe viral disease currently affecting farmed crustaceans.IMPORTANCE White spot disease is currently the most devastating viral disease in farmed crustaceans, such as shrimp and crayfish, and has resulted in a severe ecological problem for both brackish water and freshwater aquaculture areas worldwide. Efficient antiviral control of WSSV disease is still lacking due to our limited knowledge of its pathogenesis. Importantly, research on the WSSV infection mechanism is also quite meaningful for the elucidation of viral pathogenesis and virus-host coevolution, as WSSV is one of the largest animal viruses, in terms of genome size, that infects only crustaceans. Here, we found that most of the endocytic WSSV virions were directed to the endosomal delivery system, strongly facilitated by CqVCP, so that they avoided autophagic degradation and successfully delivered the viral genome into the Hpt cell nucleus for propagation. Our data point to a virus-sorting model that might also explain the escape of other enveloped DNA viruses.

An Unexpected Conjunctival Prolapse Following Frontalis Muscle Flap Transfer for Severe Ptosis.

Conjunctival prolapse may occur following ocular, eyelid, and orbital surgeries. Conjunctival prolapse usually results as a complication of maximal levator resection or cosmetic lower eyelid blepharoplasty. Here, we describe conjunctival prolapse as an unexpected complication of frontalis muscle flap transfer for severe ptosis. On postoperative day 5, the patient experienced upper eyelid swelling after closing his eyes suddenly and standing up abruptly. The conjunctiva was reddish and ballooned up, and they protruded over the eyelids. Conjunctival prolapse persisted until postoperative day 8. The patient and surgeon were concerned that this complication would affect ptosis correction and surgical outcome. U-shaped fixations were placed to suture and force the prolapsed conjunctiva back to their normal anatomical positions. At postoperative 6 months, the patient had not experienced additional issues, and he was satisfied with the appearance of his eyes. This report describes a rare clinical case of conjunctival prolapse and provides a reference for surgeons treating similar complications.

Identification of a CqCaspase gene with antiviral activity from red claw crayfish Cherax quadricarinatus.

Caspase, an aspartate specific proteinase mediating apoptosis, plays a key role in immune response. In our previous study, the expression of a caspase gene was up-regulated in a transcriptome library from the haematopoietic tissue (Hpt) cells of red claw crayfish Cherax quadricarinatus post white spot syndrome virus (WSSV) infection. To further reveal the effect of caspase on WSSV infection, we cloned this caspase gene (denominated as CqCaspase) with an open reading frame of 1062 bp, which encoded 353 amino acids with a caspase domain (CASc) containing a p20 subunit and a p10 subunit. Tissue distribution analysis indicated that the mRNA transcript of CqCaspase was widely expressed in all tested tissues with the highest expression in Hpt, while the lowest expression in muscle. To further explore the effect of CqCaspase on WSSV replication, recombinant protein of CqCaspase (rCqCaspase) was delivered into Hpt cells followed by WSSV infection, which resulted in a significantly decreased expression of both an immediate early gene IE1 and a late envelope protein gene VP28 of WSSV, suggesting that CqCaspase, possibly by the enhanced apoptotic activity, had a strong negative effect on the WSSV replication. These data together indicated that CqCaspase was likely to play a vital role in immune defense against WSSV infection in a crustacean C. quadricarinatus, which shed a new light on the mechanism study of WSSV infection in crustaceans.

Upper blepharoplasty revision technique: Correction of the high eyelid fold using the pretarsal orbicularis oculi flap.

PURPOSE: With the growing popularity of upper lid blepharoplasty, there have been increasing reports of unsatisfactory outcomes that have necessitated a revision surgery. This study aimed to evaluate aesthetic outcomes of surgical correction of the high eyelid fold using a pretarsal orbicularis oculi flap and to highlight the key practice points of this surgical procedure in secondary blepharoplasty. METHODS: A retrospective study of 31 consecutive Chinese patients who underwent revision surgeries between January 2013 and December 2015 was undertaken through a review of medical records. All these patients underwent surgical correction of high eyelid folds using a pretarsal orbicularis oculi flap, with postoperative follow-up ranging from 6 months to 4 years. Postoperative outcomes were reviewed, evaluated, and analyzed. RESULTS: In this study of 31 women who underwent secondary revision procedure of the high eyelid fold using a pretarsal orbicularis oculi muscle flap, mean follow-up time was 8.2 (range 6-48) months. All flaps survived without significant complications. There was no reported incidence of hematoma or infection in early postoperative complications. Clinical effectiveness was satisfactory in most of the patients who underwent fold repair (26/31, 83.9%). However, five patients (16.1%) expressed dissatisfaction with postoperative outcomes; of them, four patients (12.9%) had mild asymmetry, whereas surgical revision was required in only one patient (3.2%). CONCLUSION: Secondary blepharoplasty to correct the high eyelid fold is a challenging procedure for plastic surgeons. Use of the pretarsal orbicularis oculi muscle flap for correction of the high eyelid fold is safe and effective, with better biomechanics and a satisfying aesthetic outcome. This provides a novel treatment option in limited secondary revision techniques.

Successful Treatment of a Subcutaneous Abscess Caused by Hyaluronic Acid Injection in Nasal Dorsum Augmentation Via a Scarless Incision.

We report a successful treatment of a subcutaneous abscess in a 24-year-old woman caused by hyaluronic acid injection in nasal dorsum augmentation using negative pressure drainage via nasal mucosal approach.

Acute Kidney Injury among Hospitalized Children in China.

BACKGROUND AND OBJECTIVES: High-quality epidemiologic data on AKI in children are particularly lacking in developing countries. This study aimed to assess the epidemiology and clinical correlates of AKI among hospitalized children in China. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter study, in a cohort of hospitalized children aged 1 month to 18 years, from 25 general and children's hospitals in China during 2013-2015. We obtained patient-level data from the electronic hospitalization information system and laboratory databases of all children who had at least two serum creatinine tests within any 7-day window during their first 30 days of hospitalization. We identified AKI events according to the creatinine criteria of Kidney Disease Improving Global Outcomes. The in-hospital outcomes of AKI, including mortality, kidney recovery, and length of stay, were assessed. We estimated the corresponding hazard ratios using a Cox proportional hazard model, with adjustment for age, sex, comorbidities, and clinical procedures. RESULTS: A total of 19,908 (20%) patients with AKI were identified among 101,836 pediatric inpatients, of which 7220 (7%) were community acquired and 12,688 (13%) were hospital acquired. Up to 96% of these AKI events were not diagnosed on the discharge records. The cumulative incidence of AKI in infants (28%) was twice that in adolescents (12%). The profiles of risk factors differed between community-acquired and hospital-acquired AKI and varied with age. Diarrhea and sepsis were the top risk factors for community-acquired AKI, each contributing 6% of the risk. Congenital heart disease/cardiac surgery was the major risk factor for hospital-acquired AKI, contributing to 19% of cases. Exposure to nephrotoxic drugs, mostly nonsteroidal anti-inflammatory drugs and proton pump inhibitors, was common in hospitalized children and was associated with a higher risk of AKI. Death occurred in 842 out of 19,908 patients (4%) with AKI versus 450 out of 81,478 children (0.5%) without AKI. The risk of in-hospital death was higher among children with severe AKI, shock, and respiratory failure. Pediatric AKI was associated with longer hospital stay and higher daily cost, even after adjustment for covariates. CONCLUSIONS: Pediatric AKI is common and is substantially underdiagnosed in China.

The prognostic value of decreased NDRG1 expression in patients with digestive system cancers: A meta-analysis.

BACKGROUND: Digestive system cancers are recognized as associated with high morbidity and mortality. It is generally accepted that N-myc downstream-regulated gene 1 (NDRG1) is aberrantly overexpressed or downregulated in digestive system cancers, and its prognostic value remains controversial. Accordingly, we herein conducted a meta-analysis to explore whether NDRG1 expression is correlated with overall survival (OS) and clinicopathological characteristics of patients with digestive system cancers. METHODS: We systematically searched PubMed, EMBASE, and Web of Science for eligible studies up to June 6, 2017. In all, 19 publications with 21 studies, were included. RESULTS: The pooled results showed that low NDRG1 expression was significantly associated with worse OS in colorectal cancer (pooled HR = 1.67, 95% CI: 1.22-2.28, P < .001) and pancreatic cancer (pooled HR = 1.87, 95% CI: 1-3.5, P < .0001). Moreover, the relationships between low NDRG1 expression and higher OS ratio of patients with liver cancer (pooled HR = 0.44, 95% CI: 0.32-0.62, P = .009) and gallbladder cancer (pooled HR = 0.56, 95% CI: 0.23-1.38, P = .01) were observed. Nevertheless, no significant association was observed between low NDRG1 expression and OS in gastric cancer (pooled HR = 0.81, 95% CI: 0.45-1.43, P = .46) or esophageal cancer (pooled HR = 0.76, 95% CI: 0.26-2.24, P = .62). CONCLUSION: The prognostic significance of NDRG1 expression varies according to cancer type in patients with DSCs. Considering that several limitations existed in this meta-analysis, more studies are required to further assess the prognostic value of NDRG1 expression in patients with DSCs and relevant mechanisms.

2-aminopurine suppresses the TGF-ß1-induced epithelial-mesenchymal transition and attenuates bleomycin-induced pulmonary fibrosis.

The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer. We screened a series of 80 compounds for the ability to interfere with the EMT and potentially be applied as a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a fluorescent analog of guanosine and adenosine, as a candidate in this screen. Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-ß1-treated A549 lung cancer cells. Moreover, 2-AP can inhibit TGF-ß1-induced metastasis of A549 cells. This compound significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT, and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could inhibit metastasis in vitro by suppressing the TGF-ß1-induced EMT and could attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.

An Ns1abp-like gene promotes white spot syndrome virus infection by interacting with the viral envelope protein VP28 in red claw crayfish Cherax quadricarinatus.

Influenza A virus non-structural-1A binding protein (named as Ns1abp) was originally identified as a host protein from human that bound to the viral NS-1 protein. In our previous study, the expression of an Ns1abp-like gene (denoted as CqNs1abp-like gene) was found to be up-regulated in a transcriptome library from the haematopoietic tissue (Hpt) cells of red claw crayfish Cherax quadricarinatus post white spot syndrome virus (WSSV) infection. To elucidate the role of CqNs1abp-like gene involved in WSSV infection, we cloned the CqNs1abp-like gene in which the open reading frame was 2232 bp, encoding 743 amino acids with two typical domains of one BTB (Broad-Complex, Tramtrack and Bric a brac) domain at N-terminal and six Kelch domains at C-terminal. The gene expression profile showed that the mRNA transcript of CqNs1abp-like gene was widely expressed in all the tested tissues with highest expression in nerve, relatively high expression in Hpt and lowest expression in eyestalk. Importantly, both the WSSV entry and the viral replication were significantly reduced in Hpt cells after gene silencing of CqNs1abp-like gene. By using protein pull-down assay, we found that the recombinant BTB domain, six Kelch domains and CqNs1abp-like intact protein were all bound to the WSSV envelope protein VP28, respectively, in which the BTB domain showed slightly less binding affinity than that of the six Kelch domains or the recombinant intact protein. Besides, the WSSV entry into Hpt cells was clearly decreased when the virus was pre-incubated with the recombinant BTB domain, six Kelch domains, or the recombinant CqNs1abp-like intact protein, respectively, suggesting that the CqNs1abp-like gene was likely to function as a putative recognition molecular towards WSSV infection in a crustacean C. quadricarinatus. Taken together, these data shed new light on the mechanism of WSSV infection and a putatively novel target on anti-WSSV infection in crustacean farming.