Trichinella spiralis inhibits myoblast differentiation by targeting SQSTM1/p62 with a secreted E3 ubiquitin ligase.

Trichinella spiralis infection is associated with the formation of cysts within host skeletal muscle cells, thereby enabling immune evasion and subsequent growth and development; however, the pathogenic factors involved in this process and their mechanisms remain elusive. Here, we found that Ts-RNF secreted by T. spiralis is required for its growth and development in host cells. Further study revealed that Ts-RNF functions as an E3 ubiquitin ligase that targets the UBA domain of SQSTM1/p62 by forming K63-type ubiquitin chains. This modification interferes with autophagic flux, leading to impaired mitochondrial clearance and abnormal myotube differentiation and fusion. Our results established that T. spiralis increases its escape by interfering with host autophagy via the secretion of an E3 ubiquitin ligase.

Nutritional status efficacy of early nutritional support in gastrointestinal care: A systematic review and meta-analysis.

BACKGROUND: Gastrointestinal surgery is a complicated process used to treat many gastrointestinal diseases, and it is associated with a large trauma: Most patients often have different degrees of malnutrition and immune dysfunction before surgery and are prone to various infectious complications during postoperative recovery, thus affecting the efficacy of surgical treatment. Therefore, early postoperative nutritional support can provide essential nutritional supply, restore the intestinal barrier and reduce complication occurrence. However, different studies have shown different conclusions. AIM: To assess whether early postoperative nutritional support can improve the nutritional status of patients based on literature search and meta-analysis. METHODS: Articles comparing the effect of early nutritional support and delayed nutritional support were retrieved from PubMed, EMBASE, Springer Link, Ovid, China National Knowledge Infrastructure, China Biology Medicine databases. Notably, only randomized controlled trial articles were retrieved from the databases (from establishment date to October 2022). The risk of bias of the included articles was determined using Cochrane Risk of Bias V2.0. The outcome indicators, such as albumin, prealbumin, and total protein, after statistical intervention were combined. RESULTS: Fourteen literatures with 2145 adult patients undergoing gastrointestinal surgery (1138 patients (53.1%) receiving early postoperative nutritional support and 1007 patients (46.9%) receiving traditional nutritional support or delayed nutritional support) were included in this study. Seven of the 14 studies assessed early enteral nutrition while the other seven studies assessed early oral feeding. Furthermore, six literatures had "some risk of bias," and eight literatures had "low risk". The overall quality of the included studies was good. Meta-analysis showed that patients receiving early nutritional support had slightly higher serum albumin levels, than patients receiving delayed nutritional support [MD (mean difference) = 3.51, 95%CI: -0.05 to 7.07, Z = 1.93, P = 0.05]. Also, patients receiving early nutritional support had shorter hospital stay (MD = -2.29, 95%CI: -2.89 to -1.69), Z = -7.46, P < 0.0001) shorter first defecation time (MD = -1.00, 95%CI: -1.37 to -0.64), Z = -5.42, P < 0.0001), and fewer complications (Odd ratio = 0.61, 95%CI: 0.50 to 0.76, Z = -4.52, P < 0.0001) than patients receiving delayed nutritional support. CONCLUSION: Early enteral nutritional support can slightly shorten the defecation time and overall hospital stay, reduce complication incidence, and accelerate the rehabilitation process of patients undergoing gastrointestinal surgery.

Recombinant Klotho attenuates IFNγ receptor signaling and SAMHD1 expression through blocking NF-κB translocation in glomerular mesangial cells.

Interferon gamma (IFNγ) is a cytokine implicated in the pathogenesis of autoimmune diseases. SAM and HD domain-containing protein 1 (SAMHD1) is an IFNγ-inducible protein that modulates cellular dNTP levels. Mutations in the human SAMHD1 gene cause Aicardi-Goutières (AG) syndrome, an autoimmune disease sharing similar clinical features with systemic lupus erythematosus (SLE). Klotho is an anti-inflammatory protein which suppresses aging through multiple mechanisms. Implication of Klotho in autoimmune response is identified in rheumatologic diseases such as SLE. Little information exists regarding the effect of Klotho in lupus nephritis, one of the prevalent symptoms of SLE. The present study verified the effect of IFNγ on SAMHD1 and Klotho expression in MES-13 glomerular mesangial cells, a special cell type in glomerulus that is critically involved in lupus nephritis. IFNγ upregulated SAMHD1 expression in MES-13 cells through the Janus kinase-signal transducer and activator of transcription 1 (JAK-STAT1) and the nuclear factor kappa B (NFκB) signaling pathways. IFNγ decreased Klotho protein expression in MES-13 cells. Treatment of MES-13 cells with recombinant Klotho protein inhibited SAMHD1 expression by blocking IFNγ-induced NFκB nuclear translocation, but showed no effect on JAK-STAT1 signaling. Collectively, our findings support the protective role of Klotho in attenuating lupus nephritis through the inhibition of IFNγ-induced SAMHD1 expression and IFNγ downstream signaling in MES-13 cells.

3D Visualization of Whole Brain Vessels and Quantification of Vascular Pathology in a Chronic Hypoperfusion Model Causing White Matter Damage.

Chronic cerebral hypoperfusion is an important pathological factor in many neurodegenerative diseases, such as cerebral small vessel disease (CSVD). One of the most used animal models for chronic cerebral hypoperfusion is the bilateral common carotid artery stenosis (BCAS) mouse. For the therapy of CSVD and other diseases, it will be beneficial to understand the pathological alterations of the BCAS mouse, particularly vascular pathological changes. A mouse model of BCAS was used, and 8 weeks later, cognitive function of the mice was examined by using novel object recognition test and eight-arm radial maze test. 11.7 T magnetic resonance imaging (MRI) and luxol fast blue staining were used to evaluate the injury of the corpus callosum (CC), anterior commissure (AC), internal capsule (IC), and optic tract (Opt) in the cerebral white matter of mice. Three-dimensional vascular images of the whole brain of mice were acquired using fluorescence micro-optical sectioning tomography (fMOST) with a high resolution of 0.32 × 0.32 × 1.00 µm3. Then, the damaged white matter regions were further extracted to analyze the vessel length density, volume fraction, tortuosity, and the number of vessels of different internal diameters. The mouse cerebral caudal rhinal vein was also extracted and analyzed for its branch number and divergent angle in this study. BCAS modeling for 8 weeks resulted in impaired spatial working memory, reduced brain white matter integrity, and myelin degradation in mice, and CC showed the most severe white matter damage. 3D revascularization of the whole mouse brain showed that the number of large vessels was reduced and the number of small vessels was increased in BCAS mice. Further analysis revealed that the vessel length density and volume fraction in the damaged white matter region of BCAS mice were significantly reduced, and the vascular lesions were most noticeable in the CC. At the same time, the number of small vessels in the above white matter regions was significantly reduced, while the number of microvessels was significantly increased in BCAS mice, and the vascular tortuosity was also significantly increased. In addition, the analysis of caudal rhinal vein extraction revealed that the number of branches and the average divergent angle in BCAS mice were significantly reduced. The BCAS modeling for 8 weeks will lead to vascular lesions in whole brain of mice, and the caudal nasal vein was also damaged, while BCAS mice mainly mitigated the damages by increasing microvessels. What is more, the vascular lesions in white matter of mouse brain can cause white matter damage and spatial working memory deficit. These results provide evidence for the vascular pathological alterations caused by chronic hypoperfusion.

Inhibition of DNA methylation attenuates lung ischemia-reperfusion injury after lung transplantation.

OBJECTIVE: DNA methylation plays an important role in inflammation and oxidative stress. This study aimed to investigate the effect of inhibiting DNA methylation on lung ischemia-reperfusion injury (LIRI). METHODS: We adopted a completely random design for our study. Thirty-two rats were randomized into the sham, LIRI, azathioprine (AZA), and pluripotin (SC1) groups. The rats in the LIRI, AZA, and SC1 groups received left lung transplantation and intravenous injection of saline, AZA, and SC1, respectively. After 24 hours of reperfusion, histological injury, the arterial oxygen partial pressure to fractional inspired oxygen ratio, the wet/dry weight ratio, protein and cytokine concentrations in lung tissue, and DNA methylation in lung tissue were evaluated. The pulmonary endothelium that underwent hypoxemia and reoxygenation was treated with AZA or SC1. Endothelial apoptosis, chemokines, reactive oxygen species, nuclear factor-κB, and apoptotic proteins in the endothelium were studied. RESULTS: Inhibition of DNA methylation by AZA attenuated lung injury, inflammation, and the oxidative stress response, but SC1 aggravated LIRI injury. AZA significantly improved endothelial function, suppressed apoptosis and necrosis, reduced chemokines, and inhibited nuclear factor-κB. CONCLUSIONS: Inhibition of DNA methylation ameliorates LIRI and apoptosis and improves pulmonary function via the regulation of inflammation and oxidative stress.

Advances for pharmacological activities of Polygonum cuspidatum - A review.

CONTEXT: Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name 'Huzhang', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc. OBJECTIVE: This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts. METHODS: The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords. RESULTS: The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns. CONCLUSIONS: Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.

Association of Serum Interleukin-8 and Serum Amyloid A With Anxiety Symptoms in Patients With Cerebral Small Vessel Disease.

Objective: Cerebral small vessel disease (CSVD) is a clinical syndrome caused by pathological changes in small vessels. Anxiety is a common symptom of CSVD. Previous studies have reported the association between inflammatory factors and anxiety in other diseases, but this association in patients with CSVD remains uncovered. Our study aimed to investigate whether serum inflammatory factors correlated with anxiety in patients with CSVD. Methods: A total of 245 CSVD patients confirmed using brain magnetic resonance imaging (MRI) were recruited from December 2019 to December 2021. Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety symptoms of CSVD patients. Patients with HAMA scores ≥7 were considered to have anxiety symptoms. The serum levels of interleukin-1ß (IL-1ß), IL-2R, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), serum amyloid A (SAA), C-reactive protein (CRP), high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were detected. We compared levels of inflammatory factors between the anxiety and non-anxiety groups. Logistic regression analyses examined the correlation between inflammatory factors and anxiety symptoms. We further performed a gender subgroup analysis to investigate whether this association differed by gender. Results: In the fully adjusted multivariate logistic regression analysis model, we found that lower levels of IL-8 were linked to a higher risk of anxiety symptoms. Moreover, higher levels of SAA were linked to a lower risk of anxiety symptoms. Our study identified sex-specific effects, and the correlation between IL-8 and anxiety symptoms remained significant among males, while the correlation between SAA and anxiety symptoms remained significant among females. Conclusions: In this study, we found a suggestive association between IL-8, SAA, and anxiety symptoms in CSVD participants. Furthermore, IL-8 and SAA may have a sex-specific relationship with anxiety symptoms.

Multiple biochemical indices and metabolomics of Clonorchis sinensis provide a novel interpretation of biomarkers.

BACKGROUND: Clonorchiasis, an infectious disease caused by the liver fluke Clonorchis sinensis, may lead to the development of liver and gallbladder diseases, and even cholangiocarcinoma (CCA). However, the pathogenesis, host-pathogen interaction, and diagnostic markers for clonorchiasis remain unclear. METHODS: Eighteen rabbits were randomly divided into control group (n = 9) and C. sinensis-infected group (n = 9), and their plasma samples were collected at 7, 14, 28, and 63 days post-infection (dpi). Biochemical indices and metabolites in different infection periods were detected. A non-targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) approach was employed to investigate the metabolic profiles of plasma in rabbits, and related metabolic pathways of differential metabolites and correlation between candidate biochemical indices and differential metabolites were analyzed. Finally, the candidate biomarkers were verified with human samples using a targeted metabolomics method. RESULTS: The result of biochemical indices indicated C. sinensis infection would affect the liver function biochemical indices, especially alanine aminotransferase, aspartate transaminase (AST), glutamyl transpeptidase (GGT), total bile acid, high-density lipoprotein, and cholinesterase. The metabonomic results showed that 58, 212, 23, and 21 differential metabolites were identified in different phases of the infection. Multivariate statistical analysis of differential metabolites revealed distinct metabolic signatures during different phases of infection, with most of these signatures being observed at 14 dpi, which mainly influences the amino acid metabolisms. For metabolites and biochemical indices, AST, GGT, hypoxanthine, L-pipecolic acid, and D-glucuronate represented potential noninvasive biomarkers for the diagnosis of C. sinensis (P < 0.05 and AUC > 0.8). Furthermore, GGT and D-glucuronate levels were positively correlated with the infection (r(28) = 0.98, P < 0.0001) and showed excellent diagnostic performance (AUC = 0.972; 95% confidence interval, 0.921 to 1.000). CONCLUSIONS: The present results provide new insights into plasma metabolic changes in rabbits during C. sinensis infection, and the potential biomarker may be used for developing an effective method to diagnose clonorchiasis in the future.

The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation.

Background: Cerebral small vessel disease (CSVD) is a group of clinical syndromes covering all pathological processes of small vessels in the brain, which can cause stroke and serious dementia. However, as the pathogenesis of CSVD is not clear, so the treatment is limited. Endothelial cell dysfunction is earlier than clinical symptoms, such as hypertension and leukosis. Therefore, the treatment of endothelial cells is expected to be a new breakthrough. Quercetin, a flavonoid present in a variety of plants, has the function of anti-inflammation and anti-oxidation. This study aimed to investigate the protective effect of quercetin on endothelial cell injury and provide a basic theory for subsequent application in the clinic. Methods: Human brain microvascular endothelial cells (HBMECs) were cultured in vitro, and the injury model of endothelial cells was established by hypoxia and reoxygenation (H/R). The protective effects of quercetin on HBMECs were studied from the perspectives of cell viability, cell migration, angiogenesis and apoptosis. In order to further study the mechanism of quercetin, oxidative stress and endoplasmic reticulum stress were analyzed. What's more, blood-brain barrier (BBB) integrity was also studied. Results: Quercetin can promote the viability, migration and angiogenesis of HBMECs, and inhibit the apoptosis. In addition, quercetin can also activate Keap1/Nrf2 signaling pathway, reduce ATF6/GRP78 protein expression. Further study showed that quercetin could increase the expression of Claudin-5 and Zonula occludens-1. Conclusions: Our experiments show that quercetin can protect HBMECs from H/R, which contains promoting cell proliferation, cell migration and angiogenesis, reducing mitochondrial membrane potential damage and inhibiting cell apoptosis. This may be related to its antioxidation and inhibition of endoplasmic reticulum stress. At the same time, quercetin can increase the level of BBB connexin, suggesting that quercetin can maintain BBB integrity.

Rotarex mechanical thrombectomy in renal artery thrombosis: A case report.

BACKGROUND: Acute renal artery thrombosis is a relatively rare disease. Early diagnosis and emergent treatment can prevent the loss of renal function and the development of hypertension. CASE SUMMARY: We report a patient with acute renal artery thrombosis who presented to our hospital with acute-onset right flank pain and was treated by percutaneous mechanical thrombectomy using the Rotarex device. After 2 mo, right kidney function had recovered slightly. CONCLUSION: Renal artery thrombosis may lead to loss of renal function and the development of hypertension. Rotarex mechanical thrombectomy may be a viable treatment option for rapid recanalization of the renal artery in patients with renal artery thrombosis.

Percutaneous Mechanical Atherectomy Plus Thrombectomy Using the Rotarex®S Device Followed by a Drug-Coated Balloon for the Treatment of Femoropopliteal Artery In-stent Restenosis: A Prospective Single-Center, Single-Arm Efficacy Trial (PERMIT-ISR Trial).

Background: Studies investigating debulking devices with drug-coated balloons (DCBs) in the treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) are limited. We aimed to evaluate the safety and midterm outcome of percutaneous mechanical atherectomy plus thrombectomy (MATH) using the Rotarex®S (Straub Medical, Wangs, Switzerland) catheter followed by a DCB in the treatment of FP-ISR. Methods: This study was a single-center single-arm trial. Patients with symptomatic (Rutherford category 2-5) de novo restenosis lesions of FP-ISR were treated with MATH and subsequent DCB. From June 2016 to May 2018, 59 patients with FP-ISR were enrolled. The primary endpoint was target lesion revascularization (TLR) and changes in the Rutherford category of the target limb at 12 months. Secondary endpoints included primary and secondary patency at 12 months, technical success rate, major adverse events, and ankle-brachial index (ABI). Risk factors for TLR were analyzed using Cox proportional hazard model. Results: The average follow-up time was 33 ± 8 months. The rate of technical success was 88.1% (52/59). Nine patients received bailout stenting. The rate of freedom from TLR was 84.7% (50/59) at 1 year, the Rutherford category changed at 12 months were significantly improved from baseline (p < 0.01). The primary patency rates and the secondary patency at the 12-month follow-ups were 82.5 and 92.5%, respectively. The ABI changed at 12 months were significantly improved from baseline (p < 0.01). Global limb anatomic staging system (GLASS) classification III [hazard ratio (HR) 18.44, 95% CI (1.57-215.99), p = 0.020] and postoperative Rutherford classification ≥4 [HR 8.28, 95% CI (1.85-37.06), p = 0.006] were identified as independent predictors of TLR. Conclusion: Our preliminary data suggested that MATH using a Rotarex®S catheter combined with DCB angioplasty is a safe, minimally invasive, and effective treatment for FP-ISR with favorable, immediate, and midterm outcomes. Clinical Trial Registration:http://www.chictr.org.cn, identifier [ChiCTR2000041380].

Upconverting phosphor technology-based lateral flow assay for the rapid and sensitive detection of anti-Trichinella spiralis IgG antibodies in pig serum.

BACKGROUND: Trichinella spiralis is a zoonotic food-borne parasite. A disease caused by infection with T. spiralis is called trichinellosis in humans. It is important to investigate the epidemic situation and the surveillance of herds and then prevent infection in humans. Therefore, this study is to develop a rapid and sensitive diagnostic method for on-site test in domestic and wild animals. METHODS: Upconverting phosphor nanoparticles (UCNPs), an excellent optical label, were conjugated with the excretory-secretory (ES) antigens from T. spiralis muscle larvae (ML) or goat anti-rabbit IgG, and a lateral flow (LF) assay based on these probes (UCNPs-ES/goat anti-rabbit IgG) was developed for the rapid and sensitive detection of anti-T. spiralis IgG antibodies in pig serum. The assay is named the UPT-LF-ES assay. In addition, the probes were characterized, and the assay was optimized. A cut-off threshold of the assay was also identified by using 169 known negative pig samples. Performance of the assay to T. spiralis with different infective numbers, cross-reactivity with other parasitic infections, the single-blinded experiment, and coincidence were evaluated with the assay. RESULTS: The UPT-LF-ES assay was successfully constructed and optimized based on the probes of UCNPs-ES/goat anti-rabbit IgG. In the pigs infected with 100, 1000, and 10,000 ML, positive results were first presented at 35 days post-infection (dpi), 30 dpi, and 25 dpi, respectively. The assay had no cross-reaction with other parasitic infections. A single-blinded experiment indicated that the sensitivity and specificity of the UPT-LF-ES assay were 100% and 100%, respectively, the area under the receiver operating characteristic (ROC) curve was 1.000. In addition, the value detected by the UPT-LF-ES assay was significantly different between positive and negative samples. Moreover, compared with the "gold standard" magnetic stirrer method, the coincidence rate of the UPT-LF-ES assay was 87.27%, and the kappa (K) coefficient was 0.7454, showing a substantial agreement. CONCLUSIONS: The UPT-LF-ES assay is a useful point-of-care test (POCT) with T. spiralis in the detection of pig, which contributes to preventing human trichinellosis.

Hemodynamic Parameters Predict In-stent Thrombosis After Multibranched Endovascular Repair of Complex Abdominal Aortic Aneurysms: A Retrospective Study of Branched Stent-Graft Thrombosis.

Background: Branch vessel occlusion is reported in endovascular repair of aortic pathology. This study aimed to evaluate the hemodynamic indicators associated with in-stent thrombosis (IST) of a branched stent-graft (BSG) after endovascular aortic repair (EVAR) of a complex abdominal aortic aneurysm. Methods: A retrospective evaluation was performed based on the computed tomography (CT) scans and clinical data of three patients who underwent multi-branched endovascular repair. Patient-specific 3-dimensional models were reconstructed, and hemodynamic analysis was performed for IST. Hemodynamics-related parameters including time-averaged wall shear stress (TAWSS), oscillatory shear stress index (OSI), and relative residence time (RRT) were compared among the individual patients. Results: The flow velocity, TAWSS, OSI, and RRT were radically changed in the area of the IST. In BSGs, IST tended to occur in the regions of hemodynamic alteration near the bends in the device, where a decreased flow velocity (<0.6 m/s) and TAWSS (<0.8 Pa) and an elevated OSI (>0.2) and RRT (>5 s) were consistently observed. Conclusions: Hemodynamic perturbations in BSGs cause a predisposition to IST, which can be predicted by a series of changes in the flow parameters. Early hemodynamic analysis might be useful for identifying and remediating IST after multibranched endovascular repair.

Bioinformatic Prediction and Production of Four Recombinant Proteins from Different Developmental Stages of Trichinella spiralis and Testing of Their Diagnostic Sensitivity in Mice.

BACKGROUND: Trichinellosis is a serious food-borne parasitic zoonosis, thus finding high quality antigens is the key to serodiagnosis of trichinosis. This article reports the characterization and sensitivity of four recombinant proteins expressed by four genes (Wn10, Zh68, T668, and Wm5) from different developmental stages of Trichinella spiralis for the diagnosis of trichinellosis in mice. METHODS: This study was conducted in Jilin University and National Institute of Parasitic Diseases of Chinese Center for Disease Control and Prevention in 2017-2018. The structures and functions of the proteins encoded by four genes were predicted by bioinformatics analysis. The four genes were cloned and expressed, and the recombinant proteins were purified. Anti-Trichinella IgM and IgG antibodies in the sera of mice infected with T. spiralis from 1-45 d post-infection (dpi) were evaluated by ELISA. RESULTS: The optimal antigen epitopes of four proteins (P1, P2, P3, and P4) encoded by the four genes from T- and B-cells were predicted, and four purified recombinant proteins (r-P1, r-P2, r-P3, and r-P4) were successfully produced. For IgM, the antibody levels detected by the four recombinant antigens were approximately equal to the cut-off value. Anti-Trichinella IgG antibodies were first detected by r-P1 at 8 dpi, followed by r-P2, r-P3, and r-P4 at 10 dpi, 14 dpi, and 16 dpi, respectively, and the antibody levels remained high until 45 dpi. CONCLUSION: The recombinant antigens r-P1, r-P2, r-P3, and r-P4 could be antigens that react with antibodies, they showed high sensitivity in the detection of anti-Trichinella IgG antibodies in mice. Among these proteins, r-P1 may be a candidate antigen for the detection of anti-Trichinella IgG antibodies in the early infection phase and exhibited the best sensitivity among the antigens.

Development of genome-wide polymorphic microsatellite markers for Trichinella spiralis.

BACKGROUND: Trichinella nematodes are globally distributed food-borne pathogens, in which Trichinella spiralis is the most common species in China. Microsatellites are a powerful tool in population genetics and phylogeographic analysis. However, only a few microsatellite markers were reported in T. spiralis. Thus, there is a need to develop and validate genome-wide microsatellite markers for T. spiralis. METHODS: Microsatellites were selected from shotgun genomic sequences using MIcroSAtellite identification tool (MISA). The identified markers were validated in 12 isolates of T. spiralis in China. RESULTS: A total of 93,140 microsatellites were identified by MISA from 9267 contigs in T. spiralis genome sequences, in which 16 polymorphic loci were selected for validation by PCR with single larvae from 12 isolates of T. spiralis in China. There were 7-19 alleles per locus (average 11.25 alleles per locus). The observed heterozygosity (HO) and expected heterozygosity (HE) ranged from 0.325 to 0.750 and 0.737 to 0.918, respectively. The polymorphism information content (PIC) ranged from 0.719 to 0.978 (average 0.826). Among the 16 loci, markers for 10 loci could be amplified from all 12 international standard strains of Trichinella spp. CONCLUSIONS: Sixteen highly polymorphic markers were selected and validated for T. spiralis. Primary phylogenetic analysis showed that these markers might serve as a useful tool for genetic studies of Trichinella parasites.

Open surgery and endovascular repair for mycotic aortic aneurysms: Benefits beyond survival.

OBJECTIVE: Endovascular techniques have been increasingly used to treat mycotic aortic aneurysms. However, apart from survival, the potential benefits of open surgery and endovascular repair for mycotic aortic aneurysms are poorly understood. The aim of this study was to evaluate the short- and mid-term outcomes after open surgery versus endovascular repair for mycotic aortic aneurysms. METHODS: All patients treated for mycotic aortic aneurysms at Peking University People's Hospital between 2001 and 2017 were identified. Survival was analyzed using Kaplan-Meier analysis and log-rank tests. The reoperation rate was analyzed using a competing-risk analysis. RESULTS: Forty-three patients were identified. The mean follow-up time was 41 months (median, 29; range, 1-135 months). The 30-day mortality in the open surgery group was 8.7% (2/23) versus 5% (1/20) in the endovascular repair group (P = .999). The overall survival for open surgery and endovascular repair was 78% versus 75%, respectively, at 1 year, and 69% versus 41% (P = .210), respectively, at 5 years. But during the follow-up, the open surgery group demonstrated multiple benefits, including a shorter length of hospital stay (26.80 ± 14.1 days vs 42.73 ± 21.22 days, P = .026), fewer readmissions (mean 0.61 vs 1.30, P = .037), and lower infection-related reoperations (P = .018) than endovascular repair at 3 years. Subgroup analysis revealed better survival for open surgery in patients with a periaortic mass less than 20 mm (P = .03). CONCLUSIONS: There were no significant differences between endovascular repair and open surgery in survival. However, in the mid-term, the potential benefits of open surgery are favorable compared with endovascular repair, including lower infection-related reoperation rates and reduced medical burden.

Kinetics Evaluation of IgM and IgG Levels in the Mice Infected with Trichinella spiralis Experimentally Using ES Antigens from Different Developmental Stages of the Parasite.

BACKGROUND: To assay the Trichinella-specific IgM and IgG antibody responses during the early stage of infection, serum was collected from mice infected with the muscle larvae (ML) of T. spiralis (ISS534) at different dpi (days post infection) up to 60 days. METHODS: The levels of IgM and IgG antibodies in serum were measured by ES antigens from different stage of T. spiralis using the ELISA method in Shanghai, China in 2017. RESULTS: The anti-Trichinella IgM and IgG could be detected by ES antigens from the adult three days worm (Ad3) as early as 5 dpi and 8 dpi, respectively. ES antigens from the mixture of adult six days worm & new born larvae (Ad6+NBL) was similar to Ad3. When antibodies were detected by these two antigens, the levels of IgM peaked at 14 dpi and then declined from 15 dpi to 60 dpi; the IgG peaked at 20 dpi, and gradually declined, however, higher detection levels were maintained until 60 dpi. CONCLUSION: Ad3 ES antigens showed more antigenicity than Ad6+NBL ES on titer detection of IgM and IgG antibodies, and the production of Ad3 ES is easier. In terms of early diagnosis, these two antigens are better than the ML ES antigens of T. spiralis, which antibodies could not be detected before 20dpi. Ad3 ES antigens might be good candidate for the early diagnosis of trichinellosis or the mixture of Ad3 and Ad6+NBL ES might be used.

Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway.

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase (p38 MAPK) pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen's method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin (30 mg/kg) for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8-9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.

Long-read sequencing improves assembly of Trichinella genomes 10-fold, revealing substantial synteny between lineages diverged over 7 million years.

Genome assemblies can form the basis of comparative analyses fostering insight into the evolutionary genetics of a parasite's pathogenicity, host-pathogen interactions, environmental constraints and invasion biology; however, the length and complexity of many parasite genomes has hampered the development of well-resolved assemblies. In order to improve Trichinella genome assemblies, the genome of the sylvatic encapsulated species Trichinella murrelli was sequenced using third-generation, long-read technology and, using syntenic comparisons, scaffolded to a reference genome assembly of Trichinella spiralis, markedly improving both. A high-quality draft assembly for T. murrelli was achieved that totalled 63·2 Mbp, half of which was condensed into 26 contigs each longer than 571 000 bp. When compared with previous assemblies for parasites in the genus, ours required 10-fold fewer contigs, which were five times longer, on average. Better assembly across repetitive regions also enabled resolution of 8 Mbp of previously indeterminate sequence. Furthermore, syntenic comparisons identified widespread scaffold misassemblies in the T. spiralis reference genome. The two new assemblies, organized for the first time into three chromosomal scaffolds, will be valuable resources for future studies linking phenotypic traits within each species to their underlying genetic bases.