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In this paper, a sensitive biomimetic enzyme-linked immunoassay (BELISA) method based on an Au@Pt@Au composite nanozyme label was developed for histamine (HA) detection. A molecular imprinted polymer prepared directly on the 96-well plate served as a biomimetic antibody. A BELISA method was developed for HA standard solutions at concentrations ranging from 0.01 to 100.00 mg/L. Under optimal conditions, the novel BELISA method had a low limit of detection (0.069 mg/L) and high sensitivity (7.20 mg/L). The HA spiked in yellow rice wine and liqueur samples were detected by this BELISA method with the recoveries ranging from 84.28% to 108.82%. There was no significant difference of the results between the BELISA method and HPLC for the detection of HA in the red and white grape wine samples.

Oral cancer is a multifactorial cancer that affects millions of peoples worldwide. The current exploration aimed to evaluate the mechanisms that thymoquinone nanoencapsulated carrier and its effects on 7,12-Dimethylbenz[a]anthracene (DMBA) stimulated hamster buccal pouch cancer in Syrian hamster model. Nanocarrier was characterized by SEM, TEM, FTIR analysis. The incidence of tumor, and biochemicals makers was studied through standard methods. The mRNA expression level of inflammatory markers NF-κBp50, NF-κBp65, and PI3K/AKT/mTOR markers in the buccal tissues of control and experimental animals were investigated through RT-PCR analysis. In thymoquinone (TQ) loaded calcium alginate and polyvinyl alcohol carrier (TQ/Ca-alg-PVA) no squamous cell carcinogenesis developed and others moderate dysplasia revealed differentiated form of hyperplasia and keratosis. In biochemical analyses with DMBA + TQ/Ca-alg-PVA (20 mg/kg bw) orally administered hamsters showed restored the antioxidants, detoxification, xenobiotic metabolising enzymes in DMBA induced plasma and oral tissues of hamsters. Further, mRNA expression level of NF-κBp50/p65 and PI3K/AKT/mTOR were upregulated in the DMBA alone painted hamster. In contrast, these expressions were down regulated in orally TQ/Ca-alg-PVA treated experimental animals. This ability more eligible to deregulate the inflammatory and PI3K/AKT/mTOR signaling pathway that proved it suppresses anti-invasion/metastasis activity during hamster buccal pouch carcinogenesis. From this study, we recommended that TQ/Ca-alg-PVA has documented as effective chemopreventive agents, in further many molecular machineries need to study.

PurposeAtrial fibrillation (AF) is a common atrial arrhythmia. Quercetin (Que) has some advantages in the treatment of cardiovascular disease arrhythmias, but its specific drug mechanism of action needs further investigation. To explore the mechanism of action of Que in AF, core target speculation and analysis were performed using network pharmacology and molecular docking methods.MethodsQue chemical structures were obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank , STITCH, Binding DB, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF from normal tissues by GEO database differentially expressed genes. Then, the intersecting genes were obtained by online Wayne mapping tool. The intersection genes were introduced into the top five targets selected for molecular docking via protein-protein interaction (PPI) network to verify the binding activity between Que and the target proteins. GO and KEGG enrichment analysis of the intersected genes using program R was performed to further screen for key genes and key pathways.ResultsThere were 65 effective targets for Que and AF. Through further screening, the top 5 targets were IL6, VEGFA, JUN, MMP9 and EGFR. Que treatment of AF may involve signaling pathways such as lipid and atherosclerosis pathway, AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking suggests that Que has strong binding to key targets.ConclusionThis study systematically elucidates the key targets of Que treatment for AF and the specific mechanisms through network pharmacology as well as molecular docking, providing a new direction for further basic experimental exploration and clinical treatment.

Background Local recurrence is the main cause of death among patients with oral squamous cell carcinoma (OSCC). This study assessed near-infrared fluorescence (NIF) imaging and spectroscopy to monitor surgical margins intraoperatively for OSCC. Methods Cytological and animal experiments were first performed to confirm the feasibility of monitoring surgical margins with NIF imaging and spectroscopy. Then, 20 patients with OSCC were included in the clinical trials. At 6–8 h after 0.75 mg/kg indocyanine green (ICG) injection, all patients underwent surgery with NIF imaging. During the surgery, both NIF images and quantified fluorescence intensity were acquired to monitor the surgical margins. Results In cytological and animal experiments, the results showed it was feasible to monitor surgical margins with NIF imaging and spectroscopy. Fluorescence was detected in primary tumors in all patients. The fluorescence intensities of the tumor, peritumoral, and normal tissues were 398.863 ± 151.47, 278.52 ± 84.89, and 274.5 ± 100.93 arbitrary units (AUs), respectively (P < 0.05). The SBR of tumor to peritumoral tissue and normal tissues was computed to be 1.45 ± 0.36 and 1.56 ± 0.41, respectively. After primary tumor excision, the wounds showed abnormal fluorescence in four patients (4/20), and residual cancer cells were confirmed by pathological examination in two patients (2/20). Conclusion These findings confirmed the complementary value of NIF imaging during radical tumor resection of OSCC. Before tumor resection, we could utilize the fluorescence margin produced by ICG NIF imaging to determine the surgical margin. Moreover, after tumor blocks were removed, the status of surgical margin could also be evaluated rapidly by ICG NIF imaging of tumor bed and in vitro specimens.

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.

BackgroundAcrodermatitis enteropathica (AE) is a rare autosomal recessive hereditary skin disease caused by mutations in the SLC39A4 gene and is characterized by periorificial dermatitis, alopecia and diarrhoea due to insufficient zinc absorption. Only one of the three known sets of twins with AE has genetic information. This case reports the discovery of new mutation sites in rare twin patients and draws some interesting conclusions by analysing the relationship between genetic information and clinical manifestations.Case presentationHere, we report a pair of 16-month-old twin boys with AE exhibiting periorificial and acral erythema, scales and blisters, while subsequent laboratory examination showed normal plasma zinc and alkaline phosphatase levels. Further Sanger sequencing demonstrated that the patients were compound heterozygous for two unreportedSLC39A4mutations: a missense mutation in exon 5 (c.926G > T), which led to a substitution of the 309th amino acid residue cysteine with phenylalanine, a splice site mutation occurring in the consensus donor site of intron 5 (c.976 + 2 T > A). A family study revealed that the boys’ parents were heterozygous carriers of these two mutations.ConclusionWe identified a new compound heterozygous mutation in Chinese twins with AE, which consisted of two previous unreported variants in exon 5 and intron 5 of SLC39A4. We propose an up-to-date review that different mutations in SLC39A4 may exhibit different AE manifestations. In conjunction with future research, our work may shed light on genotype-phenotype correlations in AE patients and provide knowledge for genetic counselling and treatment for AE patients.

BACKGROUND Both healthcare provider-patient communication and self-care efficacy affect psychological distress, which is prevalent among patients with gastrointestinal (GI) cancers. It is essential to explore the underlying mechanism among them to relieve psychological distress. OBJECTIVE The aim of this study was to examine whether self-care efficacy mediated the association between healthcare provider-patient communication and psychological distress among patients with GI cancers. METHODS A cross-sectional study was conducted between March 2018 and May 2019 in China. In total, 219 patients with GI cancers were recruited before discharge from chemotherapy. Healthcare provider-patient communication was assessed by the revised Physician-Patient Communication Scale; patient self-care efficacy was assessed by the Strategies Used by People to Promote Health; and psychological distress was assessed by the Distress Thermometer and the Hospital Anxiety and Depression Scale. Mediation analyses were conducted to examine the mediating effect of self-care efficacy on the association between healthcare provider-patient communication and psychological distress. RESULTS A total of 54.34% of patients experienced psychological distress. Patients reported a mean score of 89.93 (SD, 13.81) for healthcare provider-patient communication and 93.91 (SD, 23.39) for self-care efficacy. Self-care efficacy completely mediated the association between healthcare provider-patient communication and psychological distress, and communication outcome was the only domain that significantly influenced self-care efficacy. CONCLUSION Psychological distress is prevalent among patients with GI cancers. Healthcare provider-patient communication, especially communication outcome, promoted patients' self-care efficacy to reduce psychological distress. IMPLICATIONS FOR PRACTICE Healthcare providers should design interventions to improve communication outcomes and eventually increase self-care efficacy to relieve psychological distress among patients with GI cancers.

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

An 80-year-old women complained of painful erythema, papules, nodules on her right wrist for 9 months. Granuloma and inflammatory infiltrates with septate fungal hyphae were observed in pathological sections. Growth of demaciatious fungus on SDA was confirmed to be Exophiala spinifera by microscopic appearance and ITS rDNA sequencing. The diagnosis of phaeohyphomycosis due to E. spinifera was established. The patient had a poor response to oral itraconazole (200 mg/d) combining with terbinafine (250 mg/d) for 6 weeks. Then, following three courses of ALA-PDT, used as adjuvant therapy, skin lesions greatly improved and remained stable after 3 months follow-up. The case suggests that ALA-PDT is an effective adjuvant treatment option for patients with recalcitrant local subcutaneous fungal infection.

Alzheimer's disease (AD) is a progressive neurodegenerative disease of the brain. It cannot be cured currently, and those suffering from AD place a great burden on their caregivers and society. AD is characterized by high levels of iron ions in the brain, which catalyze radicals that damage the neurons. Knowing that the Aβ42 peptide precipitates iron by binding iron ions at amino acid residues D1, E3, H11, H13, and H14, we synthesized a 5-repeat (HAYED) sequence peptide. By treating iron-stressed SH-SY5Y cells with it and injecting it into the cerebrospinal fluid (CSF) of naturally senescence Kunming mouse, which displaying AD-similar symptoms such as learning and memory dysfunction, neuron degeneration and high level of iron in brain, we found that HAYED (5) decreased the iron and radical levels in the cell culture medium and in the CSF. Specially, the synthesized peptide prevented cell and brain damage. Furthermore, functional magnetic resonance imaging (fMRI), Morris water maze and passive avoidance tests demonstrated that the peptide ameliorated brain blood-oxygen metabolism and slowed cognitive loss in the experimental senescence mice, and clinical and blood tests showed that HAYED (5) was innoxious to the kidney, the liver and blood and offset the AD-associated inflammation and anemia.

BackgroundThe four ERBB tyrosine kinase family members [ERBB1 (epidermal growth factor receptor, EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4)] (ERBB receptor family) have been shown, according to previous studies, to be related to the cutaneous melanoma. ERBB3 is the only member of the ERBBs that lacks tyrosine kinase activity and thus needs to dimer with other tyrosine kinases receptors to trigger the signaling pathway, while ERBB3 may dimer with all members of the ERBB family. Melanoma progression depends on activation of ERBB signaling, especially the ERBB3/ERBB2 cascade. There are lymphocytes and T cell infiltrates in melanoma. Numerous pieces of evidences indicate that local immune status plays an important role in the formation of anti-tumor immune responses. However, the relationship between the ERBBs and prognosis and immune infiltration in cutaneous melanoma is not completely clear.MethodsThe expression of the ERBBs was analyzed through the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), respectively. Immunohistochemistry of ERBBs was obtained from the Human Protein Atlas is increased before HPA database. ERBBs genes expression and mutation analysis in cutaneous melanoma from the cBioPortal. Functional annotation and Kyoto Encyclopedia of Genes and Genomes is increased before KEGG pathway enrichment analysis from the Metascape. Correlations between ERBBs and 31 genes that were close to each other and frequently altered were explored by GEPIA. Using the GEPIA database, we also investigated the relationship between ERBBs and myeloid-derived suppressor cells (MDSC) in cutaneous melanoma. The disease-free survival and different tumor stages of ERBBs were evaluated by GEPIA. The correlation of ERBBs and tumor-infiltrating immune cells and prognostic(5 years survival rates) was tested by the Tumor Immune Estimation Resource (TIMER).ResultsIn general, the expression levels of ERBB1/2 in cutaneous melanoma were lower than those in normal skin tissue. By contrast, the ERBB3 expression level was higher in cutaneous melanoma than in normal skin tissue. Low expression of ERBB1/2 and high expression of ERBB3 were detrimental to the 5 years survival of cutaneous melanoma patients (ERBB1: log-rank P: 0.03; ERBB2: log-rank P: 0.008; ERBB3: log-rank P: 0.039). ERBB4 expression may not affect the prognosis of patients with cutaneous melanoma. ERBBs may not play a role in the tumor stage and disease-free survival in cutaneous melanoma patients. The relationship between the ERBB family and 31 genes that were close to each other and frequently altered is demonstrated as the genes regulated by the ERBB family being mainly concentrated in the RAS/RAF/MEK/ERK signaling pathway. ERBB2 can induce infiltration of CD8+ T cells and B cells, while ERBB3 can induce infiltration of CD4+ T cells, CD8+ T cells, and Neutrophil cells. ERBBs are more significantly associated with M1 macrophages, dendritic cells, Th1, Th2, Th17, and Treg cellular immune markers (Cor > 0.2). ERBB2/3 were related to MDSC in cutaneous melanoma, including human mononuclear myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), and may influence the progression of cutaneous melanoma through MDSC, but the conclusion needs further probing.ConclusionThis study investigated the prognosis and immune infiltration of the ERBB family in cutaneous melanoma. Our results suggest that ERBB1/2/3 may serve as early prognostic markers and potential therapeutic targets in cutaneous melanoma.

Background Psoriasis is a chronic immune-mediated inflammatory dermatosis. Long noncoding RNAs (lncRNAs) play an important role in immune-related diseases. This study aimed to identify potential immune-related lncRNA biomarkers for psoriasis. Methods We screened differentially expressed immune-related lncRNAs biomarkers using GSE13355 (skin biopsy samples of 180 cases) from Gene Expression Omnibus (GEO). Moreover, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were performed to explore biological mechanisms in psoriasis. In addition, we performed LASSO logistic regression to identify potential diagnostic lncRNAs and further verify the diagnostic value and relationship with drug response using two validation sets: GSE30999 (skin biopsy samples of 170 cases) and GSE106992 (skin biopsy samples of 192 cases). Furthermore, we estimated the degree of infiltrated immune cells and investigated the correlation between infiltrated immune cells and diagnostic lncRNA biomarkers. Results A total of 394 differentially expressed genes (DEGs) were extracted from gene expression profile. GO and KEGG analysis of target genes found that immune-related lncRNAs were primarily associated with epidermis development, skin development, collagen-containing extracellular matrix, and glycosaminoglycan binding and mainly enriched in cytokine-cytokine receptor interaction and influenza A and chemokine signaling pathway. We found that LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1, CARMN, CCDC18-AS1, EPB41L4A-AS, and LINC01214 exhibited well diagnostic efficacy. The ROC and ROC CI were 0.944 (0.907–0.982), 0.953 (0.919–0.987), 0.822 (0.758–0.887), 0.854 (0.797–0.911), 0.957(0.929–0.985), 0.894 (0.846–0.942), and 0.964 (0.937–0.991) for LINC01137, LINC01215, MAPKAPK5-AS1, TPT1-AS1,CARMN, CCDC18-AS1, EPB41L4A-AS1, and LINC01214. LINC01137, LINC01215, and LINC01214 were correlated with drug response. LINC01137, CCDC18-AS1, and CARMN were positively correlated with activated memory CD4 T cell, activated myeloid dendritic cell (DC), neutrophils, macrophage M1, and T follicular helper (Tfh) cells, while negatively correlated with T regulatory cell (Treg). LINC01215, MAPKAPK5-AS1, TPT1-AS1, EPB41L4A-AS, and LINC01214 were negatively correlated with activated memory CD4 T cell, activated myeloid DC, neutrophils, macrophage M1, and Tfh, while positively correlated with Treg. Conclusions These findings indicated that these immune-related lncRNAs may be used as potential diagnostic and predictive biomarkers for psoriasis.

Wnt signaling is one of the key cascades regulating normal tissue development and has been tightly associated with cancer. The Wnt signaling can be subdivided into two categories: canonical & noncanonical. Noncanonical Wnt signaling pathways mainly include Wnt/PCP (planar cell polarity) signaling and Wnt-cGMP (cyclic guanosine monophosphate) /Ca2+ signaling. It has been well studied by previous researches that noncanonical Wnt signaling regulates multiple cell functions including proliferation, differentiation, adhesion, polarity, motility, and migration. The aberrant activation or inhibition of noncanonical Wnt signaling is crucial in cancer progression, exerting both oncogenic and tumor-suppressive effects. Recent studies show the involvement of noncanonical Wnt in regulating cancer cell invasion, metastasis, metabolism, and inflammation. Here, we review current insights into novel components of non-canonical signalings and describe their involvement in various cancer types. We also summarize recent biological and clinical discoveries that outline non-canonical Wnt signaling in tumorigenesis. Finally, we provide an overview of current strategies to target non-canonical Wnt signaling in cancer and challenges that are associated with such approaches.

Background: D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level provides early warning of poor prognosis. Therefore, this study aimed to assess the usefulness of D-dimer as an early indicator of prognosis in patients with coronavirus disease (COVID-19).Methods: We conducted a retrospective study of patients with COVID-19 admitted to Leishenshan Hospital in Wuhan, China, from February 15 to March 30, 2020. The final date of follow-up was April 11, 2020.Results: Of the 1,643 patients with COVID-19, 691 had elevated D-dimer levels. Their median age was 65 years. Of the patients with elevated D-dimer levels, 45% had comorbidities, with cardiovascular disease (205 [29.7%]) being the most common. Patients with elevated D-dimer were more likely to require treatment with high-flow oxygen, anticoagulation, antibiotics, and admission to the intensive care unit They were also more likely to have increased interleukin-6, monocytes, and lymphocytes. Patients with elevated D-dimer levels had significantly higher mortality than those with normal or low D-dimer levels.Conclusion: In patients with COVID-19, elevated D-dimer was associated with abnormal immunity, underlying disease, increased disease severity, and increased mortality. Taken together, D-dimer may be a marker for the early warning of disease severity and increased risk of death. These findings provide insights into the potential risk of elevated D-dimer in patients with COVID-19.

Capsaicin is a chili pepper extract with multiple therapeutic properties including anti-liver fibrosis. However, the paucity of its underlying mechanisms limited its widely clinical application.In the present study, carbon tetrachloride (CClHere, we show that capsaicin attenuates liver fibrosis progression by mediating macrophage inflammatory response. Capsaicin inhibited M1 polarization of macrophage by regulating Notch signaling leading to the reduced secretion of inflammatory cytokine TNF-α that correspondingly attenuates myofibroblasts regeneration and fibrosis formation of hepatocyte stellate cells (HSCs).Taken together, capsaicin alleviates liver fibrosis by inactivation of Notch signaling and further inhibiting TNF-α secretion from M1 macrophage. Targeting TNF-α or Notch signaling in macrophage represents a promising strategy to combat liver fibrosis.

Background Shen-ling-bai-zhu-san (SLBZS) regulates inflammation and gut microbiota which are associated with Streptococcus pneumoniae (Spn)-induced pneumonia. So, we studied the therapeutic effect of SLBZS and evaluated whether gut microbiota is associated with the effects of SLBZS in improving Spn-induced pneumonia. Methods Spn-induced pneumonia NIH mice were treated by SLBZS and cefixime. A CT scan was performed and Myeloperoxidase (MPO) activity in lung homogenates was determined using the MPO Colorimetric Assay Kit. Inflammation levels in lung homogenates were measured using ELISA. Bacterial load was coated on a TSAII sheep blood agar. Intestinal gut microbiota information was analyzed according to sequencing libraries. Results SLBZS decreased bacterial load, reduced wet/dry weight ratio, inhibited myeloperoxidase activity, reduced the neutrophils count, and ameliorated lung injury. Furthermore, SLBZS inhibited interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-2, IL-8, IL-12, and interferon-γ secretion and enhanced IL-10 secretion. These results suggest that SLBZS ameliorates lung injury in mice with Spn-induced pneumonia. Moreover, SLBZS reduced inflammatory cytokine levels in a concentration-dependent manner and increased gut microbiota abundance and diversity. After SLBZS treatment, bacteria such as Epsilonbacteraeota, Bacteroidetes, Actinobacteria, Proteobacteria, and Patescibacteria were significantly reduced, while Tenericutes and Firmicutes were significantly increased. Conclusion SLBZS ameliorates inflammation, lung injury, and gut microbiota in mice with S. pneumoniae-induced pneumonia.

ObjectiveTo investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity.MethodsWe retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT).ResultThe levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (pConclusionThe coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.

RationaleIn late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China, now spreading across the whole country and world. More data were needed to understand the clinical characteristics of the disease.ObjectivesTo study the epidemiology, clinical features and outcomes of patients with COVID-19.Methodswe performed a single center, retrospective case series study in 221 patients with laboratory confirmed SARS-CoV-2 pneumonia at a university hospital.Measurements and Main ResultsThe median age was 55.0 years and 48.9% were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe pneumonia patients, the median age of the severe patients was significantly older, and they were more likely to have chronic comorbidities. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 33.0% patients showed leukopenia and 73.8% showed lymphopenia. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications. As of February 15, 2020, 19.0% patients had been discharged and 5.4% patients died. 80% of severe cases received ICU care, and 52.3% of them transferred to the general wards due to relieved symptoms, and the mortality rate of severe patients in ICU was 20.5%.ConclusionsThe COVID-19 epidemic spreads rapidly by human-to-human transmission. Patients with elder age, chronic comorbidities, blood leukocyte/lymphocyte count, procalcitonin level, co-infection and severe complications might increase the risk of poor clinical outcomes.

Background: Since the end of 2019, coronavirus disease-2019 (COVID-19) outbreak spreads around the world We aimed to share the details of critically ill patien

Background: In late December 2019, an outbreak of acute respiratory illness, now officially named as COVID-19, or coronavirus disease 2019, emerged in Wuhan, China. We aimed to study the epidemiology and clinical features of patients diagnosed as coronavirus disease 2019 (COVID-19) and their treatment and outcome in Wuhan, China. Methods: We did a single center, retrospective case series study in patients from Zhongnan Hospital of Wuhan University, Wuhan, China. 221 admitted patients with laboratory confirmed SARS-CoV-2 infection, including 55 severe patients and 166 non-severe patients, were recruited from January 2, 2020 to February 10, 2020. Data of epidemiology, clinic, laboratory exams, radiology and treatment were collected from standardized case report forms and compared between the severe and non-severe patients with COVID-19. Specifically, the outcome of corticosteroid therapy was analyzed in the severe patients in intensive care unit (ICU). Findings: Of the 221 patients with COVID-19, 108 (48.9%) of them were male and only 8 (3.6%) patients had a history of exposure to the Huanan Seafood Market. Compared to the non-severe patients, the median age of the severe patients was significantly older (62.0 vs 51.0 years), and they were more likely to have chronic comorbidities, including hypertension, cardiovascular disease and cerebrovascular disease. Most common symptoms in severe patients were high fever, anorexia and dyspnea. On admission, 73 (33.0%) of the 221 patients showed leukopenia and 163 (73.8%) showed lymphopenia. The laboratory results showed more severity of aberrant coagulation pathway, hepatic injury, myocardial injury and kidney injury in the severe patients. In addition, the severe patients suffered a higher rate of co-infections with bacteria or fungus and they were more likely to developing complications, including acute respiratory distress syndrome (ARDS), arrhythmia, acute cardiac injury, shock and acute kidney injury. As of Feb 15, 2020, a total of 42 (19.0%) patients had been discharged and 12 (5.4%) patients died. In the 55 severe patients, 44 (80%) of them received ICU care, and 23 of them transferred to the general wards due to relieved symptoms, and the mortality rate was 21.8%. Interpretation: In this single-center case series of 221 hospitalized patients with confirmed COVID-19 in Wuhan, China, 55 severe patients with elder age and chronic comorbidities, developed more than one complication. The mortality rate was significantly higher in the severe patients compared to that in the non-severe patients (21.8% vs 0.0%). Older and male patients with higher APACHE II & SOFA scores, elevated PCT level, excessive fluid volume input, as well as the delayed use of corticosteroid might increase the risk of death in ICU. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant no. 81700493 to Dr. Pan; grant no. 81971816 to Dr. Peng). Declaration of Interests: The authors declared no conflicts. Ethics Approval Statement: This study was approved by the National Health Commission of China and Ethics Commission of Zhongnan Hospital. Written informed consent was waived by the Ethics Commission for emerging infectious disease.

Leukemic stem cells (LSCs) and hematopoietic stem cells (HSCs) are both dependent on the hypoxic bone marrow (BM) microenvironment (also known as the BM niche). There is always fierce competition between the two types of cells, and the former exhibits a greater competitive advantage than the latter via multiple mechanisms. Under hypoxia, the dynamic balance between the generation and clearing of intracellular reactive oxygen species (ROS) is conducive to maintaining a quiescent state of cells. Quiescent LSCs can reside well in the BM niche, avoiding attack by chemotherapeutic agents, which is the cause of chemotherapeutic resistance and relapse in leukemia. HSCs acquire energy mainly through anaerobic glycolysis, whereas LSCs achieve energy metabolism largely through mitochondrial oxidative respiration. Mitochondria are the primary site of ROS generation. Thus, in theory, mitochondria-mediated respiration will cause an increase in ROS generation in LSCs and a higher intracellular oxidative stress level. The sensitivity of the cells to pro-oxidant drugs increases as well, which allows for the selective clearing of LSCs by pro-oxidative therapy. However, HSCs are also highly sensitive to changes in ROS levels, and the toxic effects of pro-oxidant drugs on HSCs poses a major challenge to pro-oxidative therapy in leukemia. Given the above facts, we reviewed studies on the oxidative resistance of LSCs and the oxidative damage to HSCs under pro-oxidative therapy. An in-depth investigation into the oxidative stress status and regulatory mechanisms of LSCs and HSCs in hypoxic environments will promote our understanding of the survival strategy employed by LSCs and the mechanism of the oxidative damage to HSCs in the BM niche, thus facilitating individualized treatment of leukemia patients and helping eliminate LSCs without disturbing normal hematopoietic cells.

The superficial inferior epigastric artery (SIEA) flap is widely used in the repair of large soft tissue defects of the extremities and in breast reconstruction. Because of the high fat content of the abdomen, it has been less used for glossectomy reconstruction. Here we present a series of seven patients who each underwent reconstruction with a thin SIEA flap after resection of the tongue. There were six men and one woman (mean age 48, range 24-66 years). All patients underwent preoperative computed tomographic (CT) angiography, and colour Doppler ultrasound (US) was used to select and map the most suitable SIEA. The flap was raised above the Scarpa's layer while adjusted the plane of dissection according to the specific needs for bulk in each case. All the flaps survived; one flap required a secondary anastomosis because of a venous anastomotic embolus. The size of flap used was 5.0cm×6.0cm - 7.0cm×9.0cm, and the flap was 0.8cm-1.4cm thick. The functional outcome was evaluated at 6 - 18 months follow up, when speech and swallowing were both good in all cases. The dissection above the pubic symphysis is an important refinement of the SIEA flap, and we conclude that the thin SIEA flap is a good choice for reconstruction after excision of cancer of the tongue.

Acute lymphoblastic leukemia (ALL) is a hematological malignancy originating from B- or T-lymphoid progenitor cells. Recent studies have shown that redox dysregulation caused by overproduction of reactive oxygen species (ROS) has an important role in the development and progression of leukemia. The application of pro-oxidant therapy, which targets redox dysregulation, has achieved satisfactory results in alleviating the conditions of and improving the survival rate for patients with ALL. However, drug resistance and side effects are two major challenges that must be addressed in pro-oxidant therapy. Oxidative stress can activate a variety of antioxidant mechanisms to help leukemia cells escape the damage caused by pro-oxidant drugs and develop drug resistance. Hematopoietic stem cells (HSCs) are extremely sensitive to oxidative stress due to their low levels of differentiation, and the use of pro-oxidant drugs inevitably causes damage to HSCs and may even cause severe bone marrow suppression. In this article, we reviewed research progress regarding the generation and regulation of ROS in normal HSCs and ALL cells as well as the impact of ROS on the biological behavior and fate of cells. An in-depth understanding of the regulatory mechanisms of redox homeostasis in normal and malignant HSCs is conducive to the formulation of rational targeted treatment plans to effectively reduce oxidative damage to normal HSCs while eradicating ALL cells.

As a clonal disease of hematopoietic stem cells (HSCs), the etiology and pathogenesis of leukemia is not fully understood. Recent studies suggest that cellular homeostasis plays an essential role in maintaining the function of HSCs because dysregulation of cellular homeostasis is one of the major factors underlying the malignant transformation of HSCs. Reactive oxygen species (ROS) and autophagy, key factors regulating cellular homeostasis, are commonly observed in the human body. Autophagy can be induced by ROS through a variety of signaling pathways, and conversely inhibits ROS-induced damage to cells and tissues. ROS and autophagy coordinate to maintain cellular homeostasis. Previous studies have demonstrated that both of ROS and autophagy play important roles in the development of leukemia and are closely involved in drug resistance in leukemia. Interference with cellular homeostasis by promoting programmed leukemia cell death via ROS and autophagy has been verified to be an efficient technique in the treatment of leukemia. However, the critical roles of ROS and autophagy in the development of leukemia are largely unknown. In this review, we summarize the roles of ROS and autophagy in the pathogenesis of leukemia, which may allow the identification of novel targets and drugs for the treatment of leukemia based on the regulation of HSCs homeostasis through ROS and autophagy.

Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot. In vitro, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels. In vivo, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.

Introduction: More than 42 million people are estimated to suffer from valvular heart disease (VHD) worldwide with a prevalence of 5.3% to 7.7% in the Chinese adult population. The purpose of this study was to examine the associations between symptoms, hope, self-management behaviors, and quality of life (QOL) for preoperative patients with symptomatic VHD in a rural area of China. Method: This was a descriptive comparative study that took place in Nanning, China, between January 2015 and March 2016. The sample was 128 preoperative patients with symptomatic VHD. Data were collected using the Symptom Distress Questionnaire, Herth Hope Index, Self-Management Scale, and Minnesota Living with Heart Failure Questionnaire. Results: Data from 122 patients were included in the final analysis. Mean scores of hope, self-management, and QOL were 36.71, 55.27, and 55.56. Worse total scores of symptom severity ( r = 0.57 to 0.69, p < .001) and self-management behaviors ( r = −0.22 to −0.25, p < .05) were associated with poorer QOL. Fatigue, loss of appetite, and self-management behaviors explained 49.90% variance of QOL ( p < .001). Discussion: Fatigue, loss of appetite, and self-management influenced QOL of patients with symptomatic VHD. Interventions aimed at strengthening self-management and relieving symptoms should be tailored for patients with symptomatic VHD base on their traditional animist belief and food culture in rural areas of China such as the Zhuang Autonomous Region.

Background The purpose of this study was to analyze the association between the genetic polymorphism of genes (PAX6, SOSTDC1and FAM20B) and the susceptibility to mesiodens. Methods This study was carried out on 50 patients with mesiodens and 50 controls. The family history of each patient with mesiodens were recorded. Genomic DNA was extracted from saliva samples, and single nucleotide polymorphisms were detected in all exons and exon/intron boundaries of PAX6, SOSTDC1 and FAM20B using Sanger sequencing. The data were analyzed using pearson chi-square test with theoretical frequency ≥ 5. For theoretical frequency less than 5 but at least 1 (≤20% cell), the data were analyzed by continuity correction. For the rest, Fisher’s Exact test was used. A P-value

Morphea profunda (MP) is a variant of morphea that presents clinically as localized fibrotic plaques. Based on previous reports, there was no unified standard treatment for MP. Here we report a rare case of MP, which is the first report about treatment by hydroxychloroquine in combination with superficial X-ray. Compared with other regular therapeutic methods, this method not only produced a positive clinical effect in a short amount of time, but also caused fewer side effects.

Introduction: Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common “bypass” mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. Patient concerns: A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. Diagnosis: Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. Interventions: After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). Outcomes: The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. Conclusion: To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients.

This meta-analysis was conducted to evaluate the value of indocyanine green (ICG) in guiding sentinel lymph node biopsy (SLNB) for patients with oral cavity cancer. An electronic database search (PubMed, MEDLINE, Cochrane Library, Embase, and Web of Science) was performed from their inception to June 2020 to retrieve clinical studies of ICG applied to SLNB for oral cavity cancer. Data were extracted from 14 relevant articles (226 patients), and 9 studies (134 patients) were finally included in the meta-analysis according to the inclusion and exclusion criteria. The pooled sentinel lymph node (SLN) sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 88.0% (95% confidence interval [CI], 74.0-96.0), 64.0% (95% CI, 61.0-66.0), 2.45 (95% CI, 1.31-4.60), 0.40 (95% CI, 0.17-0.90), and 7.30 (95% CI, 1.74-30.68), respectively. The area under the summary receiver operating characteristic curve was 0.8805. In conclusion, ICG applied to SLNB can effectively predict the status of regional lymph nodes in oral cavity cancer.

BACKGROUND: The human papillomavirus (HPV) is emerging as an important risk factor in head and neck squamous cell carcinoma (HNSCC) patients. This has been observed particularly in the case of HPV16. The HPV16+ HNSCC subtype has distinct pathological, clinical, molecular, and prognostic characteristics. This study aimed to identify potential microRNAs (miRNAs) and their roles in HPV16+ HNSCC progression. METHOD: miRNA, mRNA and the clinical data of 519 HNSCC and 44 HNSCC-negative samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DEMs) in HPV16-related HNSCC tissues with prognostic value were selected. DEM levels were assessed based on clinicopathological parameters and overall survival (OS). Target genes were also predicted and functional analysis based on Gene Set Enrichment Analysis (GSEA) were then performed. RESULTS: In HPV16+ HNSCC tissues, miR-99a-3p and miR-4746-5p were significantly upregulated. In contrast, miR-411-5p was shown to be downregulated. miR-99a-3p(high)miR-411-5p(low)miR-4746-5p(high) expression could estimate improved OS and low frequent perineural invasion (PNI). Predicted target genes were enriched in cell growth, neuroepithelial cell differentiation, MAPK and FoxO signaling pathways. Epithelial mesenchymal transition (EMT) gene set and invasion related genes were downregulated in miR-99a-3p(high)miR-411-5p(low)miR-4746-5p(high) HNSCC patients. CONCLUSION: miR-99a-3p, miR-411-5p and miR-4746-5p might participate in HPV16+ HNSCC progression through EMT related pathways and affect prognosis.

Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients.In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.

The steel corrosion induced by chloride penetration is a great threaten to concrete structures, in particular exposed to marine environments. Super absorbent polymer (SAP), as a water reservoir, is probably conducive to reinforced concrete suffered from steel corrosion in marine environments. Therefore, the influence of SAP on the chloride penetration and corrosion behavior of steel in concrete were investigated using concrete mixed with 0∼2 kg/m3 SAP. The results indicate that the permeability and chloride diffusion coefficient consistently rise up with increasing with SAP dosage. Furthermore, the higher SAP dosage results in an ascending free chloride content when subjected to tidal zone. However, when exposed to atmosphere zone, the effect of SAP can be neglected. Moreover, the corrosion current of the sample with SAP are larger than that without SAP, while more corrosion products can be observed in the sample with SAP. Since the stress and strain applied on concrete and internal steel bar of specimens with SAP are apparently smaller, the propagation of crack caused by steel corrosion is probably postponed. Thus, it can be roughly concluded that for concrete subjected to marine environment, adding SAP to concrete can delay the failure process of reinforced concrete to some extent and an optimized dosage of SAP is suggested to be 1 kg/m3.