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Purpose Portal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED). Patients and methods From a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM). Results Of the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9%vs.36.5%, P=0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4%vs.21.7%, P=0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P Conclusion Hepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Supplemental Digital Content is available in the text., Background: The microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease. Methods: We used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident International Classification of Diseases–based conditions (median 10-year follow-up) and 88 quantitative traits, adjusting for age, sex, smoking status, and ethnicity. Results: Low retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling). Conclusions: Our results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

Background: Genome-wide association studies (GWAS) have revealed numerous loci for kidney function (estimated glomerular filtration rate, eGFR). The relationship of polygenic predictors of eGFR, risk of incident adverse kidney outcomes, and the plasma proteome is not known. Methods: We developed a genome-wide polygenic risk score (PRS) for eGFR by applying the LDpred algorithm to summary statistics generated from a multiethnic meta-analysis of CKDGen Consortium GWAS (N=765,348) and UK Biobank GWAS (90% of the cohort; N=451,508), followed by best parameter selection using the remaining 10% of UK Biobank (N=45,158). We then tested the association of the PRS in the Atherosclerosis Risk in Communities (ARIC) study (N=8,866) with incident chronic kidney disease, kidney failure, and acute kidney injury. We also examined associations between the PRS and 4,877 plasma proteins measured at at middle age and older adulthood and evaluated mediation of PRS associations by eGFR. Results: The developed PRS showed significant associations with all outcomes with hazard ratios (95% CI) per 1 SD lower PRS ranged from 1.06 (1.01, 1.11) to 1.33 (1.28, 1.37). The PRS was significantly associated with 132 proteins at both time points. The strongest associations were with cystatin-C, collagen alpha-1(XV) chain, and desmocollin-2. Most proteins were higher at lower kidney function, except for 5 proteins including testican-2. Most correlations of the genetic PRS with proteins were mediated by eGFR. Conclusions: A PRS for eGFR is now sufficiently strong to capture risk for a spectrum of incident kidney diseases and broadly influences the plasma proteome, primarily mediated by eGFR.

Biologically active bacterial cellulose (BC) was efficiently synthesized in situ using wine pomace and its hydrolysate. The structural and biomechanical properties together with the biological functions of the BC were investigated. Functional BC from wine pomace and its enzymatic hydrolysate were of high purity and had higher crystallinity indexes (90.61% and 89.88%, respectively) than that from HS medium (82.26%). FTIR results proved the in-situ bindings of polyphenols to the functionalized BC. Compared to BC from HS medium, wine pomace-based BC had more densely packed ultrafine fibrils, higher diameter range distributions of fiber ribbon, but lower thermal decomposition temperatures, as revealed by the SEM micrographs and DSC data. Meanwhile, wine pomace-based BC exhibited higher loads in tensile strength and higher hardness (4.95 ± 0.31 N and 5.13 ± 0.63 N, respectively) than BC in HS medium (3.43 ± 0.14 N). Furthermore, BC synthesized from wine pomace hydrolysate exhibited a slower release rate of phenolic compounds, and possessed more antioxidant activities and better bacteriostatic effects than BC from wine pomace. These results demonstrate that BC synthesized in situ from wine pomace (especially from enzymatic hydrolysate) is a promising biomolecule with a potential application in wound dressing, tissue engineering, and other biomedical fields.

Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-α in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.

Electroacupuncture (EA) is considered to have potential antidiabetic effects; however, the role of the pancreatic intrinsic nervous system (PINS) in EA-induced amelioration of type 2 diabetes (T2DM) remains unclear. Therefore, we investigated whether EA at ST25 exerts any beneficial effects on insulin resistance (IR), inflammation severity, and pancreatic β cell function via the PINS in a rat model of a high-fat diet-streptozotocin (HFD/STZ)-induced diabetes. To this end, Sprague Dawley rats were fed with HFD to induce IR, followed by STZ (35 mg/kg, i.p.) injection to establish the T2DM model. After hyperglycemia was confirmed as fasting glucose level > 16.7 mmol/L, the rats were treated with EA (2 mA, 2/15 Hz) for the next 28 days. Model rats showed increased serum glucose, insulin, IR, and TNF-α levels with a concomitant decrease in β cell function. Microscopy examination of the pancreas revealed pathological changes in islets, which reverted to near-normal levels after EA at ST25. EA improved islet cell morphology by increasing islet area and reducing vacuolation. EA at ST25 decreased transient receptor potential vanilloid 1 (TRPV1) and increased substance P (SP) and calcitonin gene-related peptide (CGRP) expression. Subsequently, insulin secretion decreased and impaired pancreatic endocrine function was restored through the TRPV1 channel (SP/CGRP)-insulin circuit. EA increased choline acetyltransferase and neuropeptide Y expression and controlled inflammation. It also enhanced the cocaine and amphetamine-regulated transcript prepropeptide expression and promoted glucagon-like peptide-1 secretion. Additionally, the electrophysiological activity of PINS during acupuncture (2.71 ± 1.72 Hz) was significantly increased compared to the pre-acupuncture frequency (0.32 ± 0.37 Hz, P < 0.05). Thus, our study demonstrated the beneficial effect of EA on β cell dysfunction via the PINS in rat models of HFD-STZ-induced T2DM.

BACKGROUND: The evidence that plethysmographic variability index (PVI), pulse pressure variation (PPV), FloTrac/Vigileo-derived stroke volume variation (SVV), and Ea(dyn) (dynamic arterial elastance) predict fluid responsiveness in children is limited by conflicting results. We aim to evaluate their accuracy and reliability to predict fluid responsiveness after induction in children aged 4–9 years undergoing major neurosurgery. METHODS: Children aged 4–9 years undergoing intracranial epileptic foci excision were enrolled. After the induction of anesthesia, fluid loading with 10 mL/kg of Ringer’s solution over 10 min was administered before surgical incision. PVI, PPV, SVV, and Ea(dyn) were measured before and within 5 min after fluid loading. Respiratory variation in aortic blood flow peak velocity (∆Vpeak) >15% at baseline, measured using transthoracic echocardiography, identified fluid “responders”. The abilities of dynamic variables to predict an increase in mean arterial pressure (MAP) of >10% following fluid loading were also assessed. RESULTS: Fourteen (31.8%) of forty-four patients were responders defined by a baseline ∆Vpeak >15%. Before fluid loading, only the PVI value was significantly different between R and NR (P=0.017). Baseline PVI showed fair diagnostic accuracy for fluid responsiveness, with an area under the curve (AUROC) of 0.735 and the cutoff value of 13%. The R group showed a significantly greater absolute change in PPV and SVV after fluid loading from baseline compared with the NR group (P=0.021 and 0.040, respectively). The absolute change in the PPV and SVV values from baseline was greater in R than those in NR (P=0.021 and 0.040, respectively). Twenty (45.5%) showed a MAP increase of >10% following fluid loading and were defined as responders. Baseline ∆Vpeak and SVV showed fair predictive values for a MAP increase of >10% (AUROC =0.758 and 0.715, respectively). CONCLUSIONS: PVI at baseline showed fair reliability to predict fluid responsiveness after anesthesia induction in mechanically ventilated children aged 4–9 years undergoing neurosurgery. Baseline ∆Vpeak and SVV were fairly predictive for an increase in MAP following fluid loading.

Background Hand, foot and mouth disease (HFMD) is caused by a variety of enterovirus serotypes and the etiological spectrum worldwide has changed since a large scale of outbreaks occurred in 1997. Methods A large number of clinical specimens of HFMD patients were collected in Xiangyang and genotyping was performed by qRT-PCR, conventional PCR amplification and sequencing. Among the 146 CV-A5 detected cases, the complete genome sequences of representative strains were determined for genotyping and for recombination analysis. Results It was found that CV-A5 was one of the six major serotypes that caused the epidemic from October 2016 to December 2017. Phylogenetic analyses based on the VP1 sequences showed that these CV-A5 belonged to the genotype D which dominantly circulated in China. Recombination occurred between the CV-A5 and CV-A2 strains with a breakpoint in the 2A region at the nucleotide 3791. Conclusions The result may explain the emergence of CV-A5 as one of the major pathogens of HFMD. A multivalent vaccine against HFMD is urgently needed to control the disease and to prevent emerging and spreading of new recombinants.

Background Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. Methods From a Chinese multicenter database, patients were categorized as AYA (aged 13–39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. Results Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age ( Conclusions Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

Microplastics (MPs) are common environmental contaminants that present a growing health concern due to their increasing presence in aquatic and human systems. However, the mechanisms behind MP effects on organisms are unclear. In this study, zebrafish (Danio rerio) were used as an in vivo model to investigate the potential risks and molecular mechanisms of the toxic effects of polyethylene MPs (45–53 μm). In the zebrafish intestine, 6, 5, and 186 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In the gills, 318, 92, and 484 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In both the intestine and the gills, Gene Ontology (GO) annotation showed that the main enriched terms were biological regulation, cellular process, metabolic process, cellular anatomical entity, and binding. KEGG enrichment analysis on DEGs revealed that the dominant pathways were carbohydrate metabolism and lipid metabolism, which were strongly influenced by MPs in the intestine. The dominant pathways in the gills were immune and lipid metabolism. The respiratory rate of gills, the activity of SOD and GSH in the intestine significantly increased after exposure to MPs compared with the control (p

Objective To understand the characteristics of DNA methyltransferase 3a (DNMT3a) in thymoma associated Myasthenia Gravis reveal its transcriptional regulator network as while as analyze the effect of DNMT3a on Rel/ nuclear factor-kappaB family (RelA/RelB) and its downstream autoimmune regulatory factor (Aire). Methods Tissues of 30 patients with thymoma, with or without myasthenia gravis (MG), were collected and the DNMT3a protein expression were evaluated through immunohistochemistry. We performed mRNA expression profiling microarray detection and analysis, and integrated the analysis by constructing protein-protein interaction networks and the integration with other database. We identified molecular difference between low and high DNMT3a in the thymoma by heatmap. We also performed PCR validation in thymoma tissues. The DNMT3a-shRNA plasmid was transfected into TEC cells, and these cells were treated with 5-aza-2-deoxycytidine, a blocker of DNMT3a. After the down-regulation of DNMT3a in TEC cells, the transcript and protein levels of RelA, RelB, Aire, and CHRNA3 were evaluated by western blotting. In addition, changes in gene expression profiles were screened through microarray technology. We performed differential gene analysis in the thymoma cohort by heatmap with R (v.4.3.0) software. Results In 30 matched tissue specimens, the expression of DNMT3a protein in thymoma with MG was lower than that in thymoma. Through mRNA expression profiling analysis, we constructed a co-expression network of DNMT3a and found direct interaction between IKZF1 and DNMT3a, and this co-expression relationship was overlappted with Cistrome DB database. We found up-regulation of 149 mRNAs and repression of 177 mRNAs in thymoma with MG compared with thymoma. Gene ontology and pathway analysis show the involvement of a multitude of genes in the mis-regulation of MG-related pathways. RNA interference significantly reduced the level of mRNA of DNMT3a, which proved that plasmid DNMT3a was effective. In comparison to the control group, the levels of DNMT3a, Aire, and CHRNA3 mRNA and protein in TEC cells transfected with DNMT3a-shRNA interference plasmid were significantly decreased, while the expression level of RelA and RelA/RelB was significantly increased. Conclusions Our study reveals the DNMT3a-NF-κB pathway has a major effect on MG, and can be used as a marker for diagnosis as well as a target for MG treatment.

BackgroundHepatocellular carcinoma (HCC), the second leading cause of cancer death worldwide, alone accounts for over half (466,100) of new cancer cases and 422,100 deaths based on the average year incidence rates of 2009 to 2011 in China. Due to unclear and complex underlying mechanisms for HCC development, effective therapy for HCC is still unavailable. The Wnt–β-catenin pathway is a critical contributor of HCC pathogenesis: 40–70% of HCCs from patients harbor the nuclear accumulation of β-catenin protein. However, the mechanisms for β-catenin activation are not fully understood.MethodsThe deletion of EHMT2 in Hep3B and Huh1 cells was achieved by transiently transfecting cells with pX459 plasmids, which carry EHMT2 specific small guide RNA (sgRNA) sequences for Cas9 protein. All experiments were performed in triplicate and repeated more than three times.ResultsIn the present study, we observed thatEHMT2(but notEHMT1) mRNA and protein levels were significantly elevated in HCC compared with normal controls. Next, the results of Ki67 staining, as well as MTT, soft-agar and xenograft assays, in wild-type andEHMT2−/−Hep3B and Huh1 cancer stem cells collectively revealed that the elevation of EHMT2 expression is required for the tumorigenesis of HCC. Meanwhile, we found that elevated EHMT2 expression contributes to the activation of Wnt–β-catenin signaling: deletion ofEHMT2in Hep3B or Huh1 cells promoted the cytoplasmic localization of β-catenin and restrained the expression of Wnt–β-catenin signaling targets such asMyc,CCND1,MMP-7, etc. We demonstrated that EMHT2 directly mediates the H3K9me2 methylation of theAPCpromoter to epigenetically silence its expression. More intriguingly, our findings also showed that UNC0642, a specific inhibitor of EHMT2, exhibits anti-tumorigenesis effects in HCC both in vitro and in vivo, which were largely abolished by deletion ofEHMT2or overexpression ofAPCin Hep3B and Huh1 cells.ConclusionAltogether, our observations emphasize that the EHMT2–APC axis is a critical contributor to Wnt–β-catenin pathway activation in HCC, and UNC0642 may be a potential candidate for target drug treatment of HCC.

BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease characterized by the proliferation, metastasis, and infiltration of smooth muscle cells in the lung and other tissues, which can be associated with tuberous sclerosis complex (TSC). The disorder of TSC has a variable expression, and there is great phenotypic variability. CASE SUMMARY A 32-year-old Chinese woman with a history of multiple renal angioleiomyolipoma presented with a productive cough persisting for over 2 wk. High-resolution chest computed tomography revealed interstitial changes, multiple pulmonary bullae, bilateral pulmonary nodules, and multiple fat density areas of the inferior mediastinum. Conventional and contrast ultrasonography revealed multiple high echogenic masses of the liver, kidneys, retroperitoneum, and inferior mediastinum. These masses were diagnosed as angiomyolipomas. Pathology through thoracoscopic lung biopsy confirmed LAM. Furthermore, high-throughput genome sequencing of peripheral blood DNA confirmed the presence of a heterozygous mutation, c.1831C>T (p.Arg611Trp), of the TSC2 gene. The patient was diagnosed with TSC-LAM. CONCLUSION We highlight a rare case of TSC-LAM and the first report of a mediastinum lymphangioleiomyoma associated with TSC-LAM.

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu’s arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P +IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = − 0.845, P +CD8 + T cells is an important source of serum IFN-γ in TAK patients.

To reveal the influence mechanism of solidification pressure on the gap width, investigations are performed on the effect of solidification pressure on the interfacial heat transfer mechanism and macroscopically averaged heat transfer coefficient between the H13 ingot and mold. With increasing solidification pressure from 0.1 to 2 MPa, there is an obvious enhancement in the heat transfer from the H13 ingot to the mold. The following quantitative relation between the macroscopically averaged heat transfer coefficient and pressure is proposed: $$ h_{i,P}^{f} = \left( {17.38P^{2} + 155.25P + 1121.7} \right)t^{ - 0.23} . $$ There are three interfacial heat transfer mechanisms, radiation and conduction through the gap between gas pockets and the slightest gap between asperities (or contacting asperities). Increasing pressure can accelerate the formation of the gap between gas pockets, and does not change the maximum value of gap width. In addition, changes in radiation and conduction through the gap between gas pockets are not the main reason for enhancing heat transfer from the ingot to the mold. In the whole process of solidification, increasing pressure is beneficial to retain the intermittent contact at asperities and reduce the macroscopically averaged width of the gap. Consequently, conduction through the slightest gap (or contacting asperities) enhanced by pressure is the major contributor to accelerating heat transfer from the ingot to the mold.

BACKGROUND Schwannomas, also known as neurinomas, are tumors that derive from Schwann cells. Gastrointestinal schwannomas are extremely rare, but the stomach is the most common site. Gastric schwannomas are usually asymptomatic. Endoscopy and imaging modalities might offer useful preliminary diagnostic information. However, to diagnose schwannoma, the immunohistochemical positivity for S-100 protein is essential, whereas CD117, CD34, SMA, desmin, and DOG-1 are negative. CASE SUMMARY A 45-year-old female was found to have a gastric mass during a medical examination, which was diagnosed as a gastric schwannoma. We performed endoscopic full-thickness resection and endoscopic purse-string suture. Pathology and immunohistochemical staining confirmed the diagnosis of gastric schwannoma through the positivity of S-100 protein. Furthermore, to exclude the misdiagnosis of gastrointestinal stromal tumor, we performed a mutational detection of the c-Kit and PDGFRA genes. Postoperative follow-up revealed that the patient recovered well. CONCLUSION Immunohistochemical staining is essential for the diagnosis of schwannoma. Endoscopic full-thickness resection is an effective treatment method for gastric schwannoma.

Background Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms. Methods Sixty male Sprague–Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. Results We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

Introduction The objective of this research was to evaluate the correlation between 3-dimensional (3D) lip vermilion (LV) morphology and skeletal patterns as well as incisor measurements in young Chinese adults. Methods In all, 240 young adults were enrolled; these included 80 patients each with skeletal Class I, Class II, and Class III malocclusions, respectively. Each sagittal skeletal pattern included 40 male and 40 female subjects. Twenty-two 3D LV measurements were obtained from 3D facial scans. Skeletal and incisor measurements were evaluated on lateral cephalograms. Correlation and regression analysis were performed between soft and hard tissue measurements. Results Six of 22 LV measurements showed significant differences between male and female subjects. The 3D LV morphology showed significant differences with respect to different skeletal patterns and sex. Adults with skeletal Class III malocclusion tended to have thinner upper vermilion and fuller lower vermilion than subjects with skeletal Class II and III malocclusion. The mandibular plane angle negatively correlated with the upper-lower vermilion midsagittal curve length and surface area ratio in adults with skeletal Class I and II malocclusion, yet the vertical facial skeletal type showed no correlation in adults with skeletal Class III malocclusion. The vermilion angle, central bow angle, vermilion height, vermilion midsagittal curve length, vermilion height and width ratio, and vermilion surface area showed a significant correlation with incisor measurements. Regression analysis found that the ANB angle was an important factor affecting the upper and lower vermilion midsagittal curve length and surface area ratio. Further, the vermilion height and height and width ratio were closely correlated with the interincisal (U1/L1) angle, whereas the central bow angle was closely correlated with the maxillary incisor torque. Conclusions Most LV morphology variables were correlated to skeletal patterns and incisor measurements. Skeletal Class III malocclusion showed significant differences in vermilion morphology. Both the sagittal and vertical skeletal pattern have effects on vermilion proportion. The incisor torque was closely correlated to vermilion shape and central bow angle and might influence the vermilion esthetics. However, the proportion of the upper and lower vermilion was mainly affected by the ANB angle.

Chemosensory receptors in the dendritic membrane of olfactory cells are critical for the molecular recognition and discrimination of odorants. Tropidothorax elegans is a major pest of agricultural, ornamental, and medicinal plants. However, very little is known about olfactory genes in T. elegans. The purpose of this study was to obtain chemosensory receptor genes by sequencing the antennal transcriptome of T. elegans using Illumina sequencing technology. We identified 153 candidate chemosensory receptors, including 121 olfactory receptors (including one olfactory receptor co-receptor), 10 ionotropic receptors (including one IR8a and one IR25a), and 22 gustatory receptors (GRs). TeleOR76, 104 and 112 displayed more highly expression level than TeleOrco. Other TeleGR genes were expressed at very low levels except TeleGR1 and 20. TeleIR76b was the most highly expressed among TeleIR genes. Our results provide valuable biological information for studies of the olfactory communication system of T. elegans.

Myofascial pain syndrome (MPS) is characterized by myofascial trigger points and fascial constrictions. At present, domestic and foreign scholars have not reached a consensus on the etiology and pathogenesis of MPS. Due to the lack of specific laboratory indicators and imaging evidence, there is no unified diagnostic criteria for MPS, making it easy to confuse with other diseases. The Chinese Association for the Study of Pain organized domestic experts to formulate this Chinese Pain Specialist Consensus on the diagnosis and treatment of MPS. This article reviews relevant domestic and foreign literature on the definition, epidemiology, pathogenesis, clinical manifestation, diagnostic criteria and treatments of MPS. The consensus is intended to normalize the diagnosis and treatment of MPS and be used by first-line doctors, including pain physicians to manage patients with MPS.

Rationale & Objective Obesity has been related to risk for chronic kidney disease. However, the associations of different measures of midlife obesity with long-term kidney function trajectories and whether they differ by sex and race are unknown. Study Design Observational study. Setting & Participants 13,496 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Predictors Midlife obesity status as measured by body mass index (BMI), waist-to-hip ratio, and predicted percent fat at baseline. Outcomes Estimated glomerular filtration rate (eGFR) calculated using serum creatinine level measured at 5 study visits, and incident kidney failure with replacement therapy (KFRT). Analytical Approach Mixed models with random intercepts and random slopes for eGFR. Cox proportional hazards models for KFRT. Results Baseline mean age was 54 years, median eGFR was 103 mL/min/1.73 m2, and median BMI was 27 kg/m2. Over 30 years of follow-up, midlife obesity measures were associated with eGFR decline in White and Black women but not consistently in men. Adjusted for age, center, smoking, and coronary heart disease, the differences in eGFR slope per 1-SD higher BMI, waist-to-hip ratio, and predicted percent fat were 0.09 (95% CI, −0.18 to 0.36), −0.25 (95% CI, −0.50 to 0.01), and −0.14 (95% CI, −0.41 to 0.13) mL/min/1.73 m2 per decade for White men; −0.91 (95% CI, −1.15 to −0.67), −0.82 (95% CI, −1.06 to −0.58), and −1.02 (95% CI, −1.26 to −0.78) mL/min/1.73 m2 per decade for White women; −0.70 (95% CI, −1.54 to 0.14), −1.60 (95% CI, −2.42 to −0.78), and −1.24 (95% CI, −2.08 to −0.40) mL/min/1.73 m2 per decade for Black men; and −1.24 (95% CI, −2.08 to −0.40), −1.50 (95% CI, −2.05 to −0.95), and −1.43 (95% CI, −2.00 to −0.86) mL/min/1.73 m2 per decade for Black women. Obesity indicators were independently associated with risk for KFRT for all sex-race groups except White men. Limitations Loss to follow-up during 3 decades of follow-up with 5 eGFR assessments. Conclusions Obesity status is a risk factor for future decline in kidney function and development of KFRT in Black and White women, with less consistent associations among men.

BACKGROUND Accidental dural puncture (ADP) and subsequent post-dural puncture headache (PDPH) remain common complications of epidural procedures for obstetric anesthesia and analgesia. No clear consensus exists on the best way to prevent PDPH after ADP. CASE SUMMARY We report our findings in twenty parturients who underwent an incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch (HES) to prevent PDPH after ADP with a 16-gauge Tuohy needle during epidural procedures. ADP with a 16-gauge Tuohy needle occurred in nine parturients undergoing a cesarean section (CS) and in eleven parturients receiving labor analgesia. An epidural catheter was re-sited at the same or adjacent intervertebral space in all patients. After CS, the epidural catheter was used for postoperative pain relief over a 48-h period. After delivery in eleven cases, epidural infusion was maintained for 24 h. Thereafter, 15 mL of 6% HES 130/0.4 was administered via the epidural catheter immediately prior to catheter removal. None of the parturients developed PDPH or neurologic deficits over a follow-up period of at least two months to up to one year postpartum. CONCLUSION An incorporated strategy of epidural analgesia followed by epidural hydroxyethyl starch may have great efficacy in preventing PDPH after ADP.

BACKGROUND As an established, simple, inexpensive, and surprisingly effective diagnostic tool, right-heart contrast echocardiography (RHCE) might help in solving a vexing diagnostic problem. If performed appropriately and interpreted logically, RHCE allows for differentiation of various usual and unusual right-to-left shunts based on the site of injection and the sequence of microbubble appearance in the heart. CASE SUMMARY A 31-year-old woman was readmitted to hospital with a 2-mo history of worsening palpitation and chest distress. Two years prior, she had been diagnosed with postpartum pulmonary embolism by conventional echocardiography and computed tomography angiography. While the latter showed no sign of pulmonary artery embolism, the former showed pulmonary artery hypertension, moderate insufficiency, and mild stenosis of the aortic valve. RHCE showed microbubbles appearing in the left ventricle, slightly delayed after right-heart filling with microbubbles; no microbubbles appeared in the left atrium and microbubbles’ appearance in the descending aorta occurred nearly simultaneous to right pulmonary artery filling with microbubbles. Conventional echocardiography was re-performed, and an arterial horizontal bidirectional shunt was found according to Doppler enhancement effects caused by microbubbles. The original computed tomography angiography findings were reviewed and found to show a patent ductus arteriosus. CONCLUSION RHCE shows a special imaging sequence for unexplained pulmonary artery hypertension with aortic valve insufficiency and simultaneous patent ductus arteriosus.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now sweeping the globe like the toppling Dominoes, and has become an alarming public health issue worldwide. To date, there have been more than 76 million confirmed cases and more than 1,690,000 deaths worldwide. SARS-CoV-2 might originate from bats and is usually transmitted through respiratory droplets and contact. The SARS-CoV-2 genome is about 30 kilobases in length, encoding 16 non-structural proteins and 4 structural proteins. The receptor-binding domain (RBD) in the S1 subunit of the spike (S) protein of SARS-CoV-2 interacts with the entry receptor angiotensin-converting enzyme 2 (ACE2) on host alveolar type II epithelial cells. The interaction causes structural changes in the S2 subunit leading to virus-host cell fusion. RNA-dependent RNA polymerase (RdRp) is vital to replication of the viral genome. ACE2 may be downregulated after infection, leading to lung edema and injury. Common symptoms of SARS-CoV-2 infection include fever, dry cough, dyspnea, fatigue, and myalgia, that is, a pneumonia that has been termed coronavirus disease-2019 (COVID-19) by the World Health Organization. COVID-19 can be fatal. The imaging findings of the lung are mostly multiple ground glass shadows and subsegmental consolidation near the pleura. SARS-CoV-2 can be detected by nucleic acid and antibody tests, virus isolation, and electron microscopy. The pathological features of COVID-19 are diffuse alveolar injury, fibrous myxoid exudate, interstitial inflammation, alveolar epithelial cell proliferation and shedding, and hyaline membrane formation. At present, antivirals are non-specific and mainly include lopinavir/ritonavir, remdesivir, and umifenovir. EK1 peptide and SARS-CoV-2-HR2P may be novel antiviral agents that can prevent infection. Convalescent plasma is generally a valid option. Although no vaccine is officially available, there are inactivated vaccines, vectored vaccines and nucleic acid-based vaccines in clinical trials. Prompt and strong measures have been taken to prevent the transmission of SARS-CoV-2 in China.

Background Pancreatic carcinoma (PAAD) is a highly malignant cancer with a poor prognosis and high mortality rate. Pumilio homologous protein 1 (PUM1) promotes cell growth, invasion, and metastasis and suppresses apoptosis in many different kinds of cancers, such as non-small-cell lung carcinoma (NSCLC), ovarian cancer and lymphocyte leukemia. However, the underlying mechanism and potential role of PUM1 in PAAD have not been investigated. Methods Bioinformatics analysis was performed using multiple databases [The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), BBCancer, Human Protein Atlas (HPA), MethSurv, cBioPortal, The Cancer Imaging Archive (TCIA), xCell, Gene Expression Omnibus (GEO)] to explore the diagnostic and prognostic role of PUM1, and the relationship between expression of PUM1 and prognosis of patients with PAAD. The analysis was further validated using the Kaplan-Meier plotter. Results PUM1 plays a role in both diagnostic and prognostic prediction. The PUM1 mRNA expression level correlates with both the prognosis and incidence of pancreatic cancer. PUM1 can serve as a potential diagnostic indicator for pancreatic cancer. Furthermore, the DNA methylation levels of PUM1 affects its oncogene function in pancreatic cancer. PUM1 can also inhibit the immune microenvironment by altering immune cell infiltration, which affects immunotherapy response in pancreatic cancer. Conclusions PUM1 takes a crucial part in the immune microenvironment and immunotherapy response of PAAD and is potentially useful for the development of novel diagnostic and treatment strategies.

Objective Quality assurance is crucial for oncological surgical treatment assessment. For rare diseases, single-quality indicators are not enough. We aim to develop a comprehensive and reproducible measurement, called the “Textbook Outcome” (TO), to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma (G-NEC) patients. Methods Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed. TO included receiving a curative resection, ≥15 lymph nodes examined, no severe postoperative complications, hospital stay ≤21 d, and no hospital readmission ≤30 d after discharge. Hospital variation in TO was analyzed using a case mix-adjusted funnel plot. Prognostic factors of survival and risk factors for non-Textbook Outcome (non-TO) were analyzed using Cox and logistic models, respectively. Results TO was achieved in 56.6% of 860 G-NEC patients. TO patients had better overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) than non-TO patients (P200 mL blood loss were independent risk factors for non-TO patients (P

Objectives: The impact of heterogeneity on gender difference for achieving clinically meaningful weight loss (cmWL) remains unclear. Here, we explored the potential gender differences in factors associated with cmWL. Methods: A total of 60,668 participants with body mass index (BMI) ≥25 kg/m2 at study entry and available BMI values at follow-up were included in this study. cmWL was defined as a weight loss of ≥5% from the study entry to follow-up. The associations of social-demographic factors, personal history of chronic diseases, lifestyle behaviors, and history of BMI with cmWL were evaluated using logistic regression models. Results: During a median follow-up of 9.13 years, 26.6% of the participants had a cmWL (30.8% for females vs. 23.1% in males; p < 0.001). Participants with older age, obesity at study entry, being more physical activity compared to 10 years ago, being relapsed smokers or consistent current smokers, having a history of chronic diseases (i.e., diabetes, osteoporosis, and stroke), cancer diagnosis during the study period, and more than 10-year follow-up were more likely to achieve cmWL in both males and females (all p < 0.05). The new smoking quitters and participants with less active in physical activity compared to 10 years ago were less likely to achieve cmWL in both males and females (all p < 0.05). Specifically, males with a history of emphysema were more likely to reach cmWL, and for females, those being overweight at 20 years old and current drinkers were more likely to reach cmWL (p < 0.05). Sensitivity analyses demonstrated similar results. Conclusion: Age, BMI status, physical activity, smoking status, family income, and health status were independent factors in males and females for weight management. However, further well-designed prospective studies are warranted to confirm our findings.

Background Cystic adenomyosis is a particular type of adenomyosis, High intensity focused ultrasound (HIFU), as a non-invasive method, has also been used to treat adenomyosis. The purpose of this study was to investigate the efficacy, safety, and feasibility of HIFU for the treatment of cystic adenomyosis. Methods Diagnosis of cystic adenomyosis was obtained through trans-vaginal ultrasound and magnetic resonance imaging (MRI). Ultrasound-guided HIFU ablation was performed under conscious sedation. The patients were evaluated by the comparison of pre-HIFU and post-HIFU imaging, as well as the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire subscales, consisting of Symptom Severity Score (SSS) and Heath Related Quality of Life (HRQL). Results HIFU was effective in treating cystic adenomyosis. No complications were observed in the four patients who were successfully treated with HIFU. Compared to preoperative symptoms and patient satisfaction, symptoms at the first follow-up observed significant improvements, with no dysmenorrhea and high health-related quality of life. During the outpatient follow-up of one month, three months, and six months postoperation, the four patients were still without dysmenorrhea and were highly satisfied with the HIFU ablation. Conclusions HIFU, as a non-invasive treatment, supplies a safe and effective possibility for the treatment of cystic adenomyosis.

BACKGROUND Pneumonia of uncertain cause has been reported in Wuhan, China since the beginning of early December 2019. In early January 2020, a novel strain of β-coronavirus was identified by the Chinese Center for Disease Control and Prevention from the pharyngeal swab specimens of patients, which was recently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There is evidence of human-to-human transmission and familial cluster outbreak of SARS-CoV-2 infection. The World Health Organization(WHO) recently declared the SARS-CoV-2 epidemic a global health emergency. As of February 17, 2020, 71329 laboratory-confirmed cases (in 25 countries, including the United States and Germany) have been reported globally. Other than its rapid transmission, the epidemiological and clinical characteristics of coronavirus disease 2019 (COVID-19) remain unclear. In December 2019, coronavirus disease (named COVID-19 by the WHO) associated with the SARS-CoV-2 emerged in Wuhan, China and spread quickly across the country. AIM To analyze the epidemiological and clinical characteristics of confirmed cases of this disease in Liaoning province, a Chinese region about 1800 km north of Wuhan. METHODS The clinical data of 56 laboratory-confirmed COVID-19 cases due to 2019-nCoV infection were analyzed. The cases originated from eight cities in Liaoning province. RESULTS The median age of the patients was 45 years, and 57.1% of them were male. No patient had been in direct contact with wild animals. Among them, 23 patients (41.1%) had resided in or traveled to Wuhan, 27 cases (48.2%) had been in contact with confirmed COVID-19 patients, 5 cases (8.9%) had been in contact with confirmed patients with a contact history to COVID-19 patients, and 1 case (1.8%) had no apparent history of exposure. Fever (75.0%) and cough (60.7%) were the most common symptoms. The typical manifestations in lung computed tomography (CT) included ground-glass opacity and patchy shadows, with 67.8% of them being bilateral. Among the patients in the cohort, 78.6% showed reduction in their lymphocyte counts, 57.1% showed increases in their C-reactive protein levels, and 50.0% showed decreases in their blood albumin levels. Eleven patients (19.6%) were admitted to intensive care unit, 2 patients (3.5%) progressed to acute respiratory distress syndrome, 4 patients (7.1%) were equipped with non-invasive mechanical ventilation, and 1 patient (1.8) received extracorporeal membrane oxygenation support. There were 5 mild cases (5/56, 8.9%), 40 moderate cases (40/56, 71.4%), 10 severe cases (10/56, 17.9%), and 1 critical case (1/56, 1.8%). No deaths were reported. CONCLUSION SARS-CoV-2 can be transmitted among humans. Most COVID-19 patients show symptoms of fever, cough, lymphocyte reduction, and typical lung CT manifestations. Most are moderate cases. The seriousness of the disease (as indicated by blood oxygen saturation, respiratory rate, oxygenation index, blood lymphocyte count, and lesions shown in lung CT) is related to history of living in or traveling to Wuhan, underlying diseases, admittance to intensive care unit, and mechanical ventilation.

Background The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging. Patients and Methods Clinicopathological data of 1,791 patients who underwent curative-intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy. Results In the development cohort, the 5-year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C-index: 0.620 vs. 0.589, p < .001), predictive homogeneity (likelihood ratio chi-square: 140.71 vs. 218.66, p < .001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p < .001), and model stability (time-dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p < .05). Conclusion We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy. Implications for Practice The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi-institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy.

Blood pressure and kidney function have a bidirectional relation. Hypertension has long been considered as a risk factor for kidney function decline. However, whether intensive blood pressure control could promote kidney health has been uncertain. The kidney is known to have a major role in affecting blood pressure through sodium extraction and regulating electrolyte balance. This bidirectional relation makes causal inference between these two traits difficult. Therefore, to examine the causal relations between these two traits, we performed two-sample Mendelian randomization analyses using summary statistics of large-scale genome-wide association studies. We selected genetic instruments more likely to be specific for kidney function using meta-analyses of complementary kidney function biomarkers (glomerular filtration rate estimated from serum creatinine [eGFRcr], and blood urea nitrogen from the CKDGen Consortium). Systolic and diastolic blood pressure summary statistics were from the International Consortium for Blood Pressure and UK Biobank. Significant evidence supported the causal effects of higher kidney function on lower blood pressure. Based on the mode-based Mendelian randomization method, the effect estimates for one standard deviation (SD) higher in log-transformed eGFRcr was -0.17 SD unit (95 % confidence interval: -0.09 to -0.24) in systolic blood pressure and -0.15 SD unit (95% confidence interval: -0.07 to -0.22) in diastolic blood pressure. In contrast, the causal effects of blood pressure on kidney function were not statistically significant. Thus, our results support causal effects of higher kidney function on lower blood pressure and suggest preventing kidney function decline can reduce the public health burden of hypertension.

Acupuncture has been used in China for thousands of years and has become more widely accepted by doctors and patients around the world. A large number of clinical studies and animal experiments have confirmed that acupuncture has a benign adjustment effect on gastrointestinal (GI) movement; however, the mechanism of this effect is unclear, especially in terms of neural mechanisms, and there are still many areas that require further exploration. This article reviews the recent data on the neural mechanism of acupuncture on GI movements. We summarize the neural mechanism of acupuncture on GI movement from four aspects: acupuncture signal transmission, the sympathetic and parasympathetic nervous system, the enteric nervous system, and the central nervous system.

The orbitofrontal cortex (OFC) encodes expected outcomes and plays a critical role in flexible, outcome-guided behavior. The OFC projects to primary visual cortex (V1), yet the function of this top-down projection is unclear. We find that optogenetic activation of OFC projection to V1 reduces the amplitude of V1 visual responses via the recruitment of local somatostatin-expressing (SST) interneurons. Using mice performing a Go/No-Go visual task, we show that the OFC projection to V1 mediates the outcome-expectancy modulation of V1 responses to the reward-irrelevant No-Go stimulus. Furthermore, V1-projecting OFC neurons reduce firing during expectation of reward. In addition, chronic optogenetic inactivation of OFC projection to V1 impairs, whereas chronic activation of SST interneurons in V1 improves the learning of Go/No-Go visual task, without affecting the immediate performance. Thus, OFC top-down projection to V1 is crucial to drive visual associative learning by modulating the response gain of V1 neurons to non-relevant stimulus., The orbitofrontal cortex (OFC) encodes expected outcomes and plays a key role in outcome-guided behavior. The authors show here that the top-down projection from the OFC to the visual cortex drives visual associative learning by modulating the response gain of V1 neurons to non-relevant stimuli.

Aplastic anemia (AA) is a T cell immune-mediated autoimmune disease. Overactivated CD8+ T cells play a leading role in the pathogenesis of AA, which may be due to disbalance in costimulatory and coinhibitory signals in T cells. In this study, we firstly investigated the expression of OX40, 4-1BB, GITR, ICOS, CTLA-4, LAG-3, and TIM-3 on CD8+ T cells from untreated patients with AA and healthy individuals (HIs) by flow cytometry. Moreover, we further analyzed the phenotype and functional characteristics of CD8+GITR+ T cells to more fully assess the T cell activation dysfunction in AA. We for the first time demonstrated significantly decreased percentage of CD8+GITR+ T cells in AA, and CD8+GITR+CTLA-4+ T cells were significantly higher in patients with AA compared with HIs. Conversely, the percentage of CD8+GITR+granzyme B+ and CD8+GITR+perforin+ T cells in AA patients was significantly reduced. Our preliminary data illustrate that the CD8+GITR+ T cell population might negatively regulate overactive T cell activation in AA.

To evaluate the health-related quality of life (HRQoL) of knee osteoarthritis (KOA) patients in China, compare their HRQoL with norm population, and examine the associations between the potential influencing factors and HRQoL. A cross-sectional study was conducted in 912 KOA patients from 4 provinces between March and November 2017. All participants were diagnosed according to the National Institute for Health and Care Excellence (NICE)’s criterion or the Chinese Medical Association (CMA)’s criterion. Recruited patients were surveyed for HRQoL using the 12-item Short Form (SF-12) and sociodemographic, disease-related factors. We assessed the associations between potential influencing factors and HRQoL using multiple linear regression models. Among the KOA patients, the mean physical component summary (PCS) of HRQoL was 40.91 ± 11.62, lower than norm (P

BackgroundDysregulation of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) form the basis of immune-mediated inflammatory diseases.Vitex trifoliaL. is a medicinal plant growing in countries such as China, India, Australia and Singapore. Its dried ripe fruits are documented in Traditional Chinese Medicine to treat ailments like rhinitis and dizziness. Its leaves are used traditionally to treat inflammation-related conditions like rheumatic pain.ObjectiveThis study aimed to investigate the effects ofV. trifolialeaf extracts prepared by different extraction methods (Soxhlet, ultrasonication, and maceration) in various solvents on cytokine production in human U937 macrophages, and identify phytoconstituents from the most active leaf extract.MethodsFresh leaves ofV. trifoliawere extracted using Soxhlet, ultrasonication, and maceration in hexane, dichloromethane, methanol, ethanol or water. Each extract was evaluated for its effects on TNF-α and IL-1β cytokine production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. The most active extract was analyzed and further purified by different chemical and spectroscopic techniques.ResultsAmongst 14 different leaf extracts investigated, extracts prepared by ultrasonication in dichloromethane and maceration in ethanol were most active in inhibiting TNF-α and IL-1β production in human U937 macrophages. Further purification led to the isolation of artemetin, casticin, vitexilactone and maslinic acid, and their effects on TNF-α and IL-1β production were evaluated. We report for the first time that artemetin suppressed TNF-α and IL-1β production. Gas chromatography-mass spectrometry analyses revealed the presence of eight other compounds. To the best of our knowledge, this is the first report of butylated hydroxytoluene, 2,4-di-tert-butylphenol, campesterol and maslinic acid inV. trifolialeaf extracts.ConclusionsIn conclusion, leaf extracts ofV. trifoliaobtained using different solvents and extraction methods were successfully investigated for their effects on cytokine production in human U937 macrophages. The findings provide scientific evidence for the traditional use ofV. trifolialeaves (a sustainable resource) and highlight the importance of conservation of medicinal plants as resources for drug discovery. Our results together with others suggest further investigation onV. trifoliaand constituents to develop novel treatment strategies in immune-mediated inflammatory conditions is warranted.

Background Levodopa-carbidopa intestinal gel (LCIG) is a new type of administration that results in steadier levodopa plasma concentrations in advanced Parkinson's disease (PD) patients and effectively reduces poor mobility and dyskinesia. Methods Electronic databases were searched up to January 1, 2018. The inclusion criteria for this review were as follows: LCIG vs oral medication in advanced PD patients. Results Five trials, with a total of 198 patients, met all the inclusion criteria. The quality score of these studies ranged from 3 to 5. Two clinical trials showed that compared with oral medication, LCIG had a better treatment effect on on-time with troublesome dyskinesia (TSD) (p = 0.02) and on-time without TSD (p < 0.00001) in advanced PD patients. In addition, four of the 5 studies showed that the LCIG may have better efficacy than oral medication for improving the scores of the UPDRS, and two studies found that LCIG demonstrated better efficacy for improving the PDQ-39 scores. The video recording results indicated a potential decline in both dyskinesia and the "off" state in LCIG-treated patients. The incidence of adverse events was not significantly different between the LCIG and oral medication groups. Conclusion Compared with oral treatment, LCIG exerts its effectiveness, mostly by reducing the time of on-time with TSD, increasing the time of on-time without TSD and scores of UPDRS and PDQ-39. It is suggesting that LCIG was likely to be a new type of administration used in clinical applications. However, due to methodological flaws, these findings should be viewed with caution, and more RCTs are needed in the field to complement our findings.

Global warming caused by CO2 emissions, and environmental pollution caused by waste polyethylene terephthalate (PET) disposal, are commonly considered as two stand-alone urgent environmental issues. However, using waste PET bottles as a carbon precursor to synthesise activated carbon (AC) for CO2 adsorption could provide a promising approach to solve the two environmental issues, simultaneously. Currently, it is still unclear whether such a solution could approach the aim of negative emissions based on a life cycle perspective. Therefore, this study assessed waste PET-derived AC coupled with temperature swing CO2 adsorption (TSA) to provide a comprehensive investigation on the potential life cycle environmental impacts. This study identified that this waste PET bottle-to-CO2 adsorbent approach could achieve negative CO2 emission, and thus provide an environmentally-friendly route to close the carbon loop. Nevertheless, the impacts of primary energy demand (PED) and water resource depletion (WU) would challenge its technical feasibility. In order to explore the key factors affecting the environmental impact, sensitivity analysis on CO2 capture, the heat source required for CO2 desorption, as well as bottle to bottle (B2B) recycling, were performed, and the major finding implies that replacing conventional heat sources by those from biomass can significantly decrease the PED impact. In addition, when recycled PET flakes were used for PET production, the life cycle impacts of WU decreased over 25%.

Objectives To prospectively compare the effectiveness and safety of percutaneous microwave ablation (PMWA) and ultrasound-guided radiofrequency ablation (USgRFA) for treating symptomatic uterine adenomyosis. Methods One hundred and thirty-three women with symptomatic uterine adenomyosis who met the inclusion criteria were enrolled in our study from October 2015 to October 2017. Sixty-eight patients underwent PMWA, and sixty-five patients underwent USgRFA. All patients were followed up for 12 months. Assessment endpoints included treatment time, percentage ablation, percentage uterine regression, symptom severity scores (SSSs), dysmenorrhea scores and adverse events. Results The mean age of the patients in our study was 39.4 ± 4.2 years (range, 35–50 years), and the median volume of uterine adenomyosis was 124.3 cm3 (range, 28.7–374.5 cm3). The mean ablation time was 16.3 ± 4.9 min (range, 5–23 min) in the MWA group, which was demonstrably superior to that of the RFA group, which was 37.5 ± 6.2 min (range, 5–39 min). The mean percentages of ablation of uterine adenomyosis were 79.7 ± 15.1% and 79.2 ± 14.2% in the MWA group and the RFA group, respectively, and showed no significant difference between the groups. The percentages of regression of uterine volume also showed no marked difference between the two groups. Changes in the dysmenorrhea scores and the SSSs after ablation were similar in the MWA group and in the RFA group, and no significant difference was found between the groups. Finally, the percentage occurrence of adverse events was the same in the two groups. Conclusions The safety and effectiveness of PMWA and USgRFA in the treatment of uterine adenomyosis were similar; however, the mean ablation time of PMWA was shorter than that of USgRFA.

Background Recurrence after atrial fibrillation(AF) ablation has many risk factors. the relationship between the recurrence rate after ablation and IR in the non-diabetic patients with AF is not clear.MethodsRetrospective cohort study enrolled AF patients without diabetes who underwent ablation between 2018~2019 in the first affiliated hospital of zhengzhou university. Homeostasis model assessment of insulin resistance (HOMA‐IR) was calculated and a value of ≥2.69 was defined as insulin resistant(IR). The patients were categaried into two groups: those with HOMA‐IR30 seconds recorded in ECG or 24‐hour Holter monitoring after 3 months blanking period.Results232 AF patients receiving ablation were enrolled and the median age was 59.5±11.3 years . There were 166 cases of paroxysmal AF and 66 cases of persistent AF. Patients with IR (n=69)were more likely to have Dyslipidemia, higher fasting blood glucose and fasting insulin than those in non-IR group. Patients with IR also were more likely to recieve antiarrhythmic drugs before ablation. After a mean follow‐up of 322±85 days, 62(26.7%) patients had documented recurrence of AF. Multivariable analysis showed that HOMA-IR value and left atrial diameter（LAD）were independent risk factors for recurrence after AF ablation (HR: 1.259, 95% CI:1.086~1.460, P=0.002; HR: 1.043, 95% CI:1.005~1.083, P=0.025; respectively).ConclusionsHOMA-IR and LAD are independent risk factors for AF recurrence after ablation in patients without diabetes.

Aim: : To investigate the analgesic effects of mangiferin (MAF) in experimental neuropathic pain (NPP) models and underlying mechanism. Methods: : Databases including Pubmed, Web of Science, Embase, Cochrane Library, China national knowledge infrastructure (CNKI), Wangfang, and Weipu were used to search for the related studies. The search terms such as MAF, NPP, meta-analysis, rat, and mouse were used in various scientific databases. Meta-analysis was used to assay the analgesic efficacy of MAF. Further, molecular docking analysis was used to measure bindings of MAF and NPP-related proteins. Results: : 6 studies were eventually included for the meta-analysis according to the inclusion and exclusion criteria. The meta-analysis results demonstrated that MAF significantly inhibited acetic acid-induced writhing responses, formalin-induced pain behavior, thermal analgesia, and mechanical allodynia as compared with the model control. However, risk of bias especially blinding existed in the included studies. The publication bias was checked by Begg's and Egger's tests. The molecular docking analysis indicated that MAF bound to 62 pain-related proteins at different levels. The top 10 predicted target proteins of MAF were glutamate carboxypeptidase II (GCPII), dopamine transporter (DAT), N-methyl-d-aspartic acid receptor 2B (NMDAR2B), transient receptor potential member 8 (TRPM8), monoamine oxidase type B (MAO-B), sodium voltage-gated channel alpha subunit 9A (SCN9A), fatty acid amide hydrolase (FAAH), gamma-secretase (GS), angiopoietin-1 (ANGPT1), and ANGPT2 based on the scores assessed by hydrogen bonding and hydrophobic interactions. Conclusions: : In summary, MAF exerts the analgesic efficacy in the murine experimental pain models, which is associated with this compound binding to the NPP-related target proteins.

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P, Patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages.

Background It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients. Methods A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs). Results In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P P = 0.044) and the occurrence of heart failure (log-rank, P P = 0.004) and heart failure (adjusted HR = 1.700 [1.347–2.147], P Conclusions An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.

Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)-immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4-butanediol diglycidyl ether (BDDE) would encapsulate di(2-ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP-containing TGA-chitosan gel (CT-D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT-D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT-D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA-immobilized chitosan allows the developed CT-D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.