TRIM3 attenuates cytokine storm caused by Dabie bandavirus via promoting Toll-like receptor 3 degradation.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by the Dabie bandavirus (DBV), and it has become a global public health threat. Cytokine storm is considered to be an important pathogenesis of critical SFTS. Tripartite motif-containing 3 (TRIM3), as a member of the TRIM protein family, may contribute to the regulation of the immune and inflammatory responses after viral infection. However, whether TRIM3 plays a major role in the pathogenesis of SFTS has not yet been investigated. Methods: TRIM3 mRNA levels were detected in PBMCs between 29 SFTS patients and 29 healthy controls by qRT-PCR. We established the pathogenic IFNAR-/- SFTS mouse model successfully by inoculating subcutaneously with DBV and testing the expression levels of TRIM3 mRNA and protein by qRT-PCR and immunofluorescence in the livers, spleens, lungs, and kidneys. TRIM3OE THP-1 cells and peritoneal macrophages extracted from TRIM3-/- mice were infected with DBV. The effect of TRIM3 on cytokines was detected by qRT-PCR and ELISA. Then we examined Toll-like receptor 3 (TLR3) and protein phosphorylation in the MAPK pathway after DBV infection using Western blot. Flow cytometry was used to verify TLR3 expression on peripheral blood monocytes in SFTS patients. We further explored the interaction between TRIM3 and TLR3 using CO-IP and Western blot. Results: Compared to healthy controls, TRIM3 mRNA expression in PBMCs is decreased in SFTS patients, especially in severe cases. TRIM3 mRNA and protein were synchronously reduced in the livers, spleens, lungs, and kidney tissues of the IFNAR-/- SFTS mice model. In the DBV-infected cell model, TRIM3 overexpression can inhibit the DBV-induced release of IL-1ß, IL-6, and TNF-α, the expression of TLR3, and protein phosphorylation in the MAPK pathway, which plays an anti-inflammatory role, while TRIM3 deficiency exacerbates the pro-inflammatory effects. We further found that TRIM3 can promote TLR3 degradation through K48-linked ubiquitination. Conclusion: TRIM3 can inhibit the production of cytokines by regulating the degradation of TLR3 through K48-linked ubiquitination, which can be a therapeutic target for improving the prognosis of SFTS.

Glp-1 Receptor Agonists Regulate the Progression of Diabetes Mellitus Complicated with Fatty Liver by Down-regulating the Expression of Genes Related to Lipid Metabolism.

Non-alcoholic fatty liver disease is mostly associated with diabetes mellitus. Dulaglutide is approved in type 2 diabetes as a hypoglycemic agent. However, its effects on liver fat and pancreatic fat contents are not evaluated yet. The objectives of the study were to evaluate the effects of dulaglutide on liver fat content, pancreatic fat content, liver stiffness, and liver enzyme levels. Patients have taken 0.75 mg subcutaneous dulaglutide each week for 4 weeks, then 1.5 mg weekly for 20 weeks plus standard treatment (metformin plus sulfonylurea and/or insulin; DS group, n = 25), or patients have taken standard treatment (metformin plus sulfonylurea and/or insulin) alone (ST group, n = 46) for type 2 diabetes management. Both groups reported a decrease in liver fat content, pancreatic fat content, and liver stiffness after interventions (p < 0.001 for all). After interventions, the DS group reported a higher decrease in liver fat content, pancreatic fat content, and liver stiffness than that of the ST group (p < 0.001 for all). After interventions, the DS group reported a higher decrease in body mass index than that of the ST group (p < 0.05). There were significant improvements in liver function tests, kidney function tests, lipid profiles, and blood counts after interventions (p < 0.05 for all). Both groups reported a decrease in body mass index after interventions (p < 0.001 for both). The DS group significantly decrease body mass index after interventions (p < 0.05) than the ST group.

A novel homozygous CYP17A1 mutation causes partial 17 α-hydroxylase/17,20-lyase deficiency in 46,XX: a case report and literature review.

Aim: 17 α-hydroxylase/17,20-lyase deficiency (17-OHD) is an extremely rare autosomal recessive disorder that typically causes hypertension, hypokalaemia, primary amenorrhoea, and the absence of secondary sex characteristics in 46,XX individuals. Partial 17-OHD is even rarer than complete 17-OHD and is prone to missed diagnosis due to its subtler symptoms. The aim of this study was to help early detection and diagnosis of partial 17-OHD.Methods: We present a case of a 41-year-old female (46,XX) patient with partial 17-OHD caused by a novel missense CYP17A1 mutation, c.391 A > C (p.T131P). This patient experienced hypertension, hypokalaemia and adrenal hyperplasia, but did not present with primary amenorrhoea or absence of secondary sex characteristics. Initially, she was misdiagnosed and underwent right and left adrenalectomy, but the procedures were ineffective. Afterward, she received a one-month treatment of 0.5 mg dexamethasone, which greatly relieved her symptoms. Additionally, we reviewed reports of thirteen other patients with partial 17-OHD in 46,XX individuals from the literature, totalling fourteen probands.Results: We found that primary amenorrhoea, hypertension, hypokalaemia, and ovarian cysts accounted for 15.4%, 42.9%, 38.5%, and 72.7% of these patients, respectively. In contrast, elevated serum progesterone was present in all patients.Conclusion: Based on our literature review, the absence of primary amenorrhoea, hypertension or hypokalaemia cannot rule out suspicion for 17-OHD in 46,XX individuals. However, an elevation in serum progesterone levels is a highly sensitive indicator for diagnosing 17-OHD.

What is the context?17-OHD is a rare cause of secondary hypertension, often with hypokalaemia, primary amenorrhoea and absence of secondary sex characteristics.Partial 17-OHD is an even rarer subtype of 17-OHD, with subtler symptoms.There are few reports concerning partial 17-OHD, especially in 46,XX patients.What is new?We reported a case of a 46,XX patient with partial 17-OHD caused by a novel missense CYP17A1 mutation, c.391 A > C (p.T131P).We also conducted a literature review to summarise the clinical, hormonal and genetic characteristics of fourteen 46,XX probands with partial 17-OHD.From the literature review, we found that:Most 46,XX patients with partial 17-OHD presented with partial pubic hair, breast development, oligomenorrhea or secondary amenorrhoea, normotension, and/or normokalemia.All 46,XX patients with partial 17-OHD presented with elevated serum progesterone.However, the relationship between in vitro enzyme activities of the 17-hydroxylase and/or17,20-lyase and clinical severity is still unclear.What is the impact?The current study can help early detection and diagnosis of partial 17-OHD.

Retracted and Republished from: "Gut Microbiota Mediates the Therapeutic Effect of Monoclonal Anti-TLR4 Antibody on Acetaminophen-Induced Acute Liver Injury in Mice".

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury (ALI) in Western countries. Many studies have shown that the gut microbiota plays an important role in liver injury. Currently, the only approved treatment for APAP-induced ALI is N-acetylcysteine; therefore, it is essential to develop new therapeutic agents and explore the underlying mechanisms. We developed a novel monoclonal anti-Toll-like receptor 4 (TLR4) antibody (ATAB) and hypothesized that it has therapeutic effects on APAP-induced ALI and that the gut microbiota may be involved in the underlying mechanism of ATAB treatment. Male C57BL/6 mice were treated with APAP and ATAB, which produced a therapeutic effect on ALI and altered the members of the gut microbiota and their metabolic pathways, such as Roseburia, Lactobacillus, Akkermansia, and the fatty acid pathway, etc. Furthermore, we verified that purified short-chain fatty acids (SCFAs) could alleviate ALI. Moreover, a separate group of mice that received feces from the ATAB group showed less severe liver injury than mice that received feces from the APAP group. ATAB therapy also improved gut barrier functions in mice and reduced the expression of the protein zonulin. Our results revealed that the gut microbiota plays an important role in the therapeutic effect of ATAB on APAP-induced ALI. IMPORTANCE In this study, we found that a monoclonal anti-Toll-like receptor 4 antibody can alleviate APAP-induced acute liver injury through changes in the gut microbiota, metabolic pathways, and gut barrier function. This work suggested that the gut microbiota can be a therapeutic target of APAP-induced acute liver injury, and we performed foundation for further research.

Cyclophilin A causes severe fever with thrombocytopenia syndrome virus-induced cytokine storm by regulating mitogen-activated protein kinase pathway.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) has become a global threat to public health since its first report in China in 2009. However, the pathogenesis of SFTS virus (SFTSV) in humans remains unclear. Also, there are no effective therapeutics for SFTS. Cyclophilin A (CyPA) regulates protein folding and trafficking involved in various viral infectious diseases, but its role in SFTSV infection has not been elucidated. Methods: We detected plasma CyPA levels in 29 healthy subjects and 30 SFTS patients by ELISA. In THP-1 cells and normal human peripheral blood mononuclear cells (PBMCs), SFTSV-induced extracellular CyPA (eCyPA) was also detected by ELISA. In THP-1, the effects of CyPA on Mitogen-activated protein kinase (MAPK) pathway and NF-κB were determined by Western blot. We validated the interaction between CypA and CD147 by human recombinant CyPA (hrCyPA) and the CD147 inhibitor. Effects of CyPA inhibitor Cyclosporine A (CsA) on cytokines and SFTSV replication in THP-1 cells was also detected. 8-week-old Interferon-α/ß Receptor (IFNAR) knockout (IFNAR-/-) C57BL/6 mice were divided into mock group, 106TCID50 SFTSV (Untreated) group and 106TCID50 SFTSV+CsA (CsA-treated) group. The changes of body weight, animal behavior and survival time of each group were recorded. Blood samples were collected from tail vein regularly. After death, the liver, spleen, lung, kidney and brain were collected for pathological HE staining and SFTSV-NP immunohistochemical staining. Results: Compared to healthy subjects and SFTS patients in the febrile phase of the disease, plasma CyPA levels in SFTS patients at the multi-organ dysfunction (MOD) phase showed significantly elevated (P < 0.01). Extracellular CyPA activates the MAPK pathway by binding to CD147 in THP-1 infected with SFTSV. CsA inhibits the pro-inflammatory and promoting replication effects of CyPA after SFTSV infection in vitro. In vivo, CsA can prolong the survival time and delay the weight loss of SFTSV mice. CsA reduces multi-organ dysfunction in IFNAR-/- mice infected with SFTSV. Discussion: Our results indicate that CyPA is associated with SFTSV-induced cytokine storm, which can be a potential target for SFTS therapy.

The clinical significance and function of EGFR mutation in TKI treatments of NSCLC patients.

BACKGROUND: EGFR mutations widely exists in NSCLC patients, which are involved in cancer development. OBJECTIVE: The function of EGFR mutations in the resistance to TKI treatments of NSCLC was evaluated to provide theoretical support for the clinical management of NSCLC patients. METHODS: A total of 150 NSCLC patients including 118 patients with EGFR mutation and 32 without, were included in this study. The EGFR mutation status and subtypes were analyzed in recruited patients. The distribution of EGFR mutation subtypes and their association with clinicopathological features were also assessed. The prognostic value of EGFR mutation was evaluated by the overall survival of recruited patients. The function of EGFR mutation was estimated, in vitro, in the TKI resistant NSCLC cells with different subtypes of EGFR mutation. RESULTS: The exon 19 deletion was the most common subtype of EGFR mutation in the enrolled patients followed by the exon 21 L858R point mutation. The EGFR mutations were closely associated with the differentiation degree and the histological types of NSCLC cases. EGFR mutation was an independent prognostic factor of NSCLC with a close relationship with the overall survival of patients. The exon 20 T790M mutation results in the erlotinib resistance through the PI3K/Akt signaling pathway. CONCLUSIONS: The EGFR mutation is a critical factor in the prognosis and for the resistance to TKI treatment in NSCLC. The exon 20 T790M mutation was involved in the erlotinib resistance through PI3K/Akt signaling pathway.

Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (Review).

Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical features of SFTS on presentation include fever, thrombocytopenia, leukocytopenia and gastrointestinal symptoms. The mortality rate is estimated to range between 5­30% in East Asia. However, SFTSV infection is increasing on an annual basis globally and is becoming a public health problem. The transmission cycle of SFTSV remains poorly understood, which is compounded by the pathogenesis of SFTS not being fully elucidated. Since the mechanism underlying the host immune response towards SFTSV is also unclear, there are no effective vaccines or specific therapeutic agents against SFTS, with supportive care being the only realistic option. Therefore, it is now crucial to understand all aspects of the host­virus interaction following SFTSV infection, including the antiviral states and viral evasion mechanisms. In the present review, recent research progress into the possible host immune responses against SFTSV was summarized, which may be useful in designing novel therapeutics against SFTS.

Efficacy and Safety of Pharmacological and Physical Therapies for Bell's Palsy: A Bayesian Network Meta-Analysis.

Objective: The objective was to comprehensively assess the efficacy and safety of all pharmacological and physical treatments (short-term, ≤ 1 month) for patients with acute Bell's palsy. Methods: The electronic databases PubMed, Web of Science, Embase, Cochrane Library, and CNKI were searched for the randomized controlled trials comparing two or more regimens in patients with the Bell's palsy to be included in a Bayesian network meta-analysis. Odds ratios and CIs for the primary outcome of the House-Brackmann scale and secondary outcomes of sequelae (synkinesis and crocodile tears) and adverse events were obtained and subgroup analyses of steroids and antivirals were conducted. Results: A total of 26 studies representing 3,609 patients having undergone 15 treatments matched our eligibility criteria. For facial recovery, acupuncture plus electrical stimulation, steroid plus antiviral plus Kabat treatment, and steroid plus antiviral plus electrical stimulation were the top three options based on analysis of the treatment ranking (probability = 84, 80, and 77%, respectively). Steroid plus antiviral plus electrical stimulation had the lowest rate of sequelae but were more likely to lead to mild adverse events. Subgroup analysis revealed that methylprednisolone and acyclovir were likely to be the preferred option. Conclusions: This network meta-analysis indicated that combined therapies, especially steroid plus antiviral plus Kabat treatment, were associated with a better facial function recovery outcome than single therapy. Other physical therapies, such as acupuncture plus electrical stimulation, may be a good alternative for people with systemic disease or allergies. More high-quality trials of physical regimens are needed in the future. Systematic Review Registration: Our registered PROSPERO number is CRD42021275486 and detailed information can be found at https://www.crd.york.ac.uk/PROSPERO/.

Gut Microbiota Mediates the Therapeutic Effect of Monoclonal Anti-TLR4 Antibody on Acetaminophen-Induced Acute Liver Injury in Mice.

Acetaminophen (APAP) overdose is one of the most common causes of acute liver injury (ALI) in Western countries. Many studies show that the gut microbiota plays an important role in liver injury. Currently, the only approved treatment for APAP-induced ALI is N-acetylcysteine; therefore, it is essential to develop new therapeutic agents and explore the underlying mechanisms. We developed a novel monoclonal anti-Toll-like receptor 4 (TLR4) antibody (ATAB) and hypothesized that it has therapeutic effects on APAP-induced ALI and that gut microbiota may be involved in the underlying mechanism of ATAB treatment. Male C57BL/6 mice were treated with APAP and ATAB, which produced a therapeutic effect on ALI and altered the gut microbiota and their metabolic pathway, such as Roseburia, Lactobacillus, Akkermansia, and the fatty acid pathway, etc. Furthermore, we verified that purified short-chain fatty acids (SCFAs) could alleviate ALI. Moreover, a separate group of mice that received feces from the ATAB group showed less severe liver injury compared with the mice receiving feces from the APAP group. ATAB therapy also improved the gut barrier functions in mice and reduced the expression of protein zonulin. Our results revealed that gut microbiota plays an important role in the therapeutic effect of ATAB on APAP-induced ALI. IMPORTANCE In this study, we found the monoclonal anti-Toll-like receptor 4 antibody can alleviate APAP-induced acute liver injury through the change of the gut microbiota, metabolic pathways, and gut barrier function. This work suggested the gut microbiota can be the therapeutic target of the APAP-induced acute liver injury, and we performed the fundamental research for further research.

Preparation of layering-structured magnetic fluorescent liposomes and labeling of HepG2 cells.

BACKGROUND: At present, surgical resection and chemotherapy are still the main treatments for hepatocellular carcinoma and other cancers, but the curative effect and survival rate are not ideal. OBJECTIVE: In this study, we aim to prepare a carrier with low toxicity, high biocompatibility and targeted transport for the treatment of hepatocellular carcinoma. METHODS: CdSe quantum dots (QDs) modified with oleic acid were synthesized. Then hydrophobic CdSe QDs and hydrophilic super-paramagnetic Fe3O4 particles were encapsulated into different layers of liposomes to form magnetic fluorescent liposomes (MFLs). MFLs in the aqueous would quickly drift towards the external magnet and the entire process was clearly observed with fluorescence microscope. The fluorescence spectra revealed that the fluorescence properties of MFLs were similar to that of CdSe QDs. RESULTS: QDs had an average size of 3.32 nm with good fluorescence properties. The size of MFLs was about 100 nm (transmission electron microscopy (TEM) analysis showed the average size of MFLs was about 82.8 nm and dynamic light scattering (DLS) detection showed 111.9 nm). After being cultured with MFLs for 8 h, HepG2 cells were labeled by MFLs, and good fluorescence images were obtained. MTT analysis also expressed their good biocompatibility. CONCLUSION: The prepared MFLs had multi-function and could be used as ideal drug carriers.

Metabolic syndrome and its components are associated with thyroid volume in adolescents.

OBJECTIVE: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. METHODS: A total of 1097 school students (610 males and 487 females, ages 12-15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. RESULTS: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (ß = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (ß = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. CONCLUSIONS: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.

Significant Benefits of Afatinib and Apatinib in a Refractory Advanced NSCLC Patient Resistant to Osimertinib: A Case Report.

EGFR-tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for NSCLC. However, acquired drug resistance often occurs after treatment with EGFR-TKIs. EGFR T790M and C797S mutations are the most common resistance mechanism in patients who failed from first- and third- generation EGFR TKI treatments, respectively. However, there is no standard of care for NSCLC harboring EGFR T790M and C797S in-cis. The present case reports a 69-year-old Chinese man with advanced NSCLC harboring EGFR exon 19-deletion, T790M, cis-C797S, and HER2 amplification who was heavily pre-treated. The patient was then given a combination of afatinib and apatinib and achieved a PFS of more than 10 months. This case showed that afatinib plus apatinib may be a promising therapy for patients with EGFR 19Del-T790M-cis-C797S mutant and HER2 amplified NSCLC.

Assaying of Cu2+ with near-infrared l-cysteine-capped CdSeTe/CdS quantum dots and its effect on cell imaging.

Near-infrared (NIR) core-shell CdSeTe/CdS quantum dots (QDs) modified with l-cysteine were synthesized in aqueous solution. The QDs had a special NIR-emitting spectrum, high fluorescence stability and low cytotoxicity. In addition, they exhibited an obvious fluorescence quenching when Cu2+ was present. An NIR nanosensor was prepared for rapidly, sensitively, and selectively determining Cu2+ in solution quantitatively and monitoring the changes in Cu2+ in cells with fluorescence imaging in a semiquantitative way. The linear relationship between the relative fluorescence intensity (F0 /F) and the concentration of Cu2+ from 5.12 × 10-8  M to 2.56 × 10-5  M in solution was observed using an NIR fluorescence spectrophotometer with R2 equal to 0.9958. Moreover, in the experiment with the fluorescence microscope, F0 /F versus the concentration of Cu2+ from 5.00 × 10-8  M to 7.68 × 10-6  M also showed a good linear relationship with R2 equal to 0.9817. Practical water sample ion detecting experiments had good accuracy and recovery rates. Cell experiments showed that the NIR imaging intensity of cells was inversely proportional to the concentration of copper ions, therefore NIR QDs have great potential for detection of metal ions in solution and in cells.

Hypoxia in utero increases the risk of pulmonary hypertension in rat offspring and is associated with vasopressin type­2 receptor upregulation.

Pulmonary hypertension (PH) in newborns and adults is a disease that can lead to right heart failure and result in a shorter lifespan. PH was induced by maintaining pregnant rats in a hypoxic chamber for 4 h twice a day, from days 7­21 of pregnancy. Hypoxia was confirmed by a decrease in the partial pressure of oxygen (PaO2) and the oxygen saturation (SaO2) of arterial blood in the aorta. The body weight of newborns from hypoxic rats was ~20% decreased compared with the control newborns of normoxic rats. The vascular wall thickness/vascular diameter values of hypoxia treated pubs were increased compared with that of control newborns 7 days after birth; however, it decreased to similar levels than in the control group after 3 months, and then further decreased to significantly lower levels than in the control group at 6 months after birth. At birth, the lung tissues of newborns from hypoxic rats exhibited an increase in the levels of mRNA and proteins associated with PH such as HIF­1α, HIF­2α, V2R, TGF­ß, TNF­α, Ang­2 and α­SMA. At 3 and 6 months after birth, the levels of both V2R mRNA and protein in offspring from hypoxic rats were at least 2­fold higher, whereas the expression of all other factors decreased compared with the control offspring. By contrast, HIF­2α and Ang­2 expression levels were significantly increased in the 6­month­old control offspring from normoxic rats. V2R overexpression in pups induced by hypoxia in maternal rats was sustained until their adulthood. V2R may be a marker for detecting PH.

Comprehensive Effects of Near-Infrared Multifunctional Liposomes on Cancer Cells.

Multifunctional theranostic systems are a recent important development of medical research. We combined the characteristics of near-infrared luminescent quantum dots and thermosensitive magnetoliposomes to develop a multifunctional nano-diagnostic material. This system is based on near-infrared magnetic thermosensitive liposomes, which encapsulate drugs and can control drug localization and release. After incubating cancer cells with the liposomes, the state of the cells was analyzed in real time by near-infrared imaging. Cell viability was significantly inhibited by heat treatment or alternating magnetic field treatment, which thus improved the anti-cancer properties of the liposomes. In the future, by combining near-infrared imaging technology and an external high-frequency alternating magnetic field, we could not only detect cancer cells noninvasively but also conduct image-guided treatments for cancer.

MiR-96 induced non-small-cell lung cancer progression through competing endogenous RNA network and affecting EGFR signaling pathway.

OBJECTIVES: Non-small cell lung cancer (NSCLC) has become a serious global health problem in the 21st century, and tumor proliferation and metastasis are the leading causes of death in patients with lung cancer. The present study aimed to verify the function of miR-96 and miR-96 in relation to competing with endogenous RNA regulatory network in NSCLC progression including proliferation and metastasis. MATERIALS AND METHODS: Clinical data of miR-96 expression was collected from StarBase 2.0 developed by Sun Yat-sen University. We used wound-healing, transwell and MTT assays to measure migration, invasion and proliferation of NSCLC cell lines after different treatment. Quantitative real time PCR and western blot were used to test differential genes expression. In order to identify target between genes (FOXO1 and DUSP1) and miR-96, luciferase assay was used. Luciferase activities in FOXO1 and DUSP1 wild type plasmid groups were compared to mutant groups. RESULTS: qRT-PCR and online database results indicated that miR-96 is highly associated with NSCLC when compared to normal patients. In addition, miR-96 indeed induced migration, invasion and proliferation of NSCLC cell line. In addition, FOXO1 and DUSP1 are targets of miR-96 and these three molecules form competing endogenous RNA network. miR-96 related competing endogenous RNA network affects cell metastasis via epidermal growth factor receptor (EGFR) signaling. CONCLUSION: miR-96 can be considered as one of tumor-inducer and form competing endogenous RNA network with FOXO1 and DUSP1, which affects downstream EGFR signaling.

Efficacy of continuous intravenous pumping of insulin for patients with diabetes complicated with perianal abscess and the effect on inflammatory cytokines.

Efficacy of insulin with different administrations for patients with diabetes complicated with perianal abscess and the effect on serum inflammatory cytokines were investigated. One hundred and sixty-seven patients with type 2 diabetes who underwent radical operation of perianal abscess in Jinhua Hospital of Zhejiang University from January 2014 to December 2016 were analyzed. Before and after the operation, 89 patients who received continuous intravenous pumping of insulin for blood glucose control were set as an observation group, and 78 patients who received intermittent subcutaneous injection of insulin as a control group. The operative efficacy, wound healing time and 1-week postoperative growth of the granulation tissue were scored and compared. Fasting blood glucose (FBG) and 2 h postprandial blood glucose (2hPBG) before and after treatment were recorded and compared. Fasting venous blood was extracted before and on the 3rd and 7th days after operation to detect and compare serum inflammatory cytokines including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Patients in the observation group had significantly higher total effective rate of the operation than that in the control group (P<0.05), and significantly shorter wound healing time and significantly lower growth score of the granulation tissue (P<0.05). Before treatment, there was no significant difference between the two groups in FBG and 2hPBG (P>0.05). After treatment, FBG and 2hPBG were significantly lower than those before treatment (P<0.050), and FBG and 2hPBG after treatment in the observation group were significantly lower than those in the control group (P<0.05). In conclusion, insulin pumps for injection during the perioperative period of patients with diabetes complicated with perianal abscess can better control the patients' blood glucose, improve the operative efficacy and promote the patients' postoperative healing. Moreover, continuous intravenous pumping of insulin is significantly better than traditional intermittent subcutaneous injection of it in controlling inflammation, so it is worthy of application.

L-noradrenaline functionalized near-infrared fluorescence CdSeTe probe for the determination of urea and bioimaging of HepG2 Cells.

In this paper, near-infrared (NIR) light emitting L-noradrenaline functionalized CdSeTe QDs (NA-CdSeTe) were synthesized and applied to the biosensing of urea. When the pH value of NA-CdSeTe solution was adjusted from neutral to alkalinity, the noradrenaline on the surface of QDs would turn to quinone, which triggered the fluorescence quenching of NA-CdSeTe probe due to the charge transfer interactions between QDs and the proximal quinone. Based on the fact that the hydrolysis of urea in the presence of urease would release OH- and slightly change the pH value of the solution, the fluorescence intensity of NA-CdSeTe QDs could be linked to the enzymatic degradation of urea. The novel urea-biosensing system could effectively determinate urea in the dynamic concentration range from 0.057 to 13mmol/L. Furthermore, NA-CdSeTe probe could serve as an "optical window" for the bioimaging of urea with high selectivity in the serum samples and HepG2 cells. The urea-bioimaging system could effectively probe urea in the dynamic concentration range from 0.2 to 5mmol/L. This NIR probe was excellent candidate not only for its sensitive with urea but also its real-time bioimaging. We expected that this NIR probe based strategy could pave the way for developing simple, no enzyme immobilization required and good sensitive method related detections for further medical applications.