Comparison of Modified Above-Knee and Conventional Surgery with the Stripping of the Great Saphenous Vein of Varicose Veins of the Lower Extremities: A Retrospective Study.

OBJECTIVE: To compare the clinical effects of modified above-knee and conventional surgery with the stripping of the great saphenous vein of varicose veins of the lower extremities. METHODS: Clinical data of patients with a varicose vein of the lower extremity from May 2016 to May 2018 were collected. A retrospective study was conducted on the patients receiving modified above-knee and conventional surgery with the great saphenous vein stripping. The baseline characteristics and long-term follow-up data were compared between the groups. RESULTS: There were no significant differences in baseline characteristics between the two groups (P > 0.05). The surgeries were successfully performed by the same group of surgeons under local anesthesia and neuraxial anesthesia. The hospital stay, operation time, intraoperative blood loss, total length, and number of incisions in the above-knee group were comparable to those in the conventional surgery group (P > 0.05). The incidence of saphenous nerve injury and subcutaneous hematoma in the above-knee group was lower than that in the conventional surgery group (P < 0.05). There were no significant differences in recurrent varicose vein incidences (P > 0.05). After surgery, the venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ-14) scores of both groups were higher than those before operation (P < 0.05). There was no significant difference in VCSS score or CIVIQ-14 scores between the two groups postoperation (P > 0.05). At 24 months after surgery, the above-knee group (71.8%) and conventional surgery group (73.2%) resulted in changes of at least two CEAP-C clinical classes lower than baseline, respectively. CONCLUSION: The modified above-knee technique can ensure clinical outcomes, reduce intraoperative blood loss and complication incidences, and shorten the operative time. This gives evidence that the modified above-knee technique is worthy of clinical application.

Liver Fibrosis in the Natural Course of Chronic Hepatitis B Viral Infection: A Systematic Review with Meta-Analysis.

BACKGROUND: Quantitative data are limited on the natural course of liver fibrosis in patients with chronic HBV infection (CHB). AIMS: To estimate the prevalence of fibrosis status including non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis throughout the natural course of CHB. METHODS: We searched Cochrane library, EMBASE, PubMed, SCOPUS, Web of Science, and ScienceDirect from January 1993 to November 2019 for studies with histologic data on liver fibrosis in CHB natural course. CHB course was defined based on current criteria for identifying infection phases as recommended by international clinical practice guidelines, including the HBeAg-positive immune-tolerant, HBeAg-positive immune-active, HBeAg-negative immune-inactive, HBeAg-negative immune-reactive, and HBsAg-negative phases. Pooled prevalence rate of fibrosis status at each phase was obtained from random-effect meta-analyses. RESULTS: Thirty-three studies with 9,377 adult participants (23.8-49.0 age years; 45.5-88.6% males) were eligible and finally included. The estimated prevalence of non-fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis was, for HBeAg-positive immune-tolerant phase: 31.2% (95%CI 15.6-46.7), 16.9% (95%CI 7.8-26.1), 5.4% (95%CI 0.0-11.2), and 0.0% (95%CI 0.0-1.5); HBeAg-positive immune-active phase: 6.9% (95%CI 3.6-10.2), 50.6% (95%CI 39.2-61.9), 32.1% (95%CI 24.2-40.0), and 12.8% (95%CI 8.6-17.0); HBeAg-negative immune-inactive phase: 32.4% (95%CI 0.0-100.0), 24.8% (95%CI 4.5-45.1), 3.0% (95%CI 0.0-8.3), and 0.0% (95%CI 0.0-1.0); and HBeAg-negative immune-reactive phase: 6.3% (95%CI 3.5-9.2), 50.3% (95%CI 38.9-61.7), 30.3% (95%CI 20.9-39.6), and 10.0% (95%CI 6.6-13.5), respectively. There was only one study for HBsAg-negative phase, thus not allowing further meta-analyses. CONCLUSIONS: Fibrosis risk persists through CHB natural course. These data can support risk estimation in clinical practice and provide reference for noninvasive investigation.

Advanced glycation end products induce endothelial hyperpermeability via ß-catenin phosphorylation and subsequent up-regulation of ADAM10.

Endothelial hyperpermeability is the initial event in the development of diabetic microvascular complications, and advanced glycation end products (AGEs) are suggested to cause much of the endothelial hyperpermeability associated with diabetes mellitus, but the molecular mechanism remains to be characterized. ß-catenin reportedly plays dual functions in maintaining normal endothelial permeability by serving both as an adhesive component and a signal transduction component. Here, we found that AGEs induced the phosphorylation of ß-catenin at residues Y654 and Y142 and the endothelial hyperpermeability was reversed when the two residues were blocked. In mechanism, phosphorylation of Y654 was blocked by Src inactivation, whereas phosphorylation of Y142 was reduced by a focal adhesion kinase inhibitor. ß-catenin Y654 phosphorylation induced by AGEs facilitated the dissociation of vascular endothelial (VE)-cadherin/ß-catenin and the impairment of adherens junctions (AJs), whereas ß-catenin Y142 phosphorylation favoured the dissociation of ß-catenin and α-catenin. Further investigation revealed that ß-catenin Y142 phosphorylation was required for AGEs-mediated ß-catenin nuclear translocation, and this nuclear-located ß-catenin subsequently activated the TCF/LEF pathway. This pathway promotes the transcription of the Wnt target, ADAM10 (a disintegrin and metalloprotease 10), which mediates VE-cadherin shedding and leads to further impairment of AJs. In summary, our study showed the role of ß-catenin Y654 and Y142 phosphorylation in AGEs-mediated endothelial hyperpermeability through VE-cadherin/ß-catenin/α-catenin dissociation and up-regulation of ADAM10, thereby advancing our understanding of the underlying mechanisms of AGEs-induced microvascular hyperpermeability.

HULC functions as an oncogene in ovarian carcinoma cells by negatively modulating miR-125a-3p.

The aberrant expression of highly upregulated in liver cancer (HULC) has been reported to participate in ovarian cancer development. A recent research has revealed that HULC-modulated microRNAs (miRNAs) in tumorigenesis. To confirm the functions of HULC on tumorigenesis of ovarian, we explored the effects of HULC expression on ovarian cancer cell development, as well as the underlying mechanism. We transfected SKOV3 cells with pEX-HULC, sh-HULC, and miR-125a-3p mimic as well as their corresponding negative controls (pEX-3, sh-NC, and NC) to alter the expression of HULC and miR-125a-3p, which were analyzed by quantitative reverse transcription PCR (qRT-PCR). Expression of proteins associated with cell cycle, apoptosis, and signaling pathways was determined by Western blot assay. The proliferation, apoptosis, migration, and invasion were explored by bromodeoxyuridine (BrdU) incorporation assay, Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) method, and transwell migration and invasion assays, respectively. HULC overexpression promoted proliferation, migration, and invasion, while inhibited apoptosis of SKOV3 cells. In addition, HULC negatively regulated the expression of miR-125a-3p. Besides, miR-125a-3p mimic reversed the effects of HULC on proliferation, migration, and invasion as well as apoptosis of SKOV3 cells. Moreover, we found that HULC enhanced phosphorylated expression of regulatory factors in phosphatidylinositol 3 kinase/protein kinase B/mammalian targets of rapamycin (PI3K/AKT/mTOR) signaling pathway by downregulating expression of miR-125a-3p. Overexpression of HULC promoted ovarian carcinoma development by activating PI3K/AKT/mTOR signaling pathway via downregulating miR-125a-3p.

Lignin xanthate resin-bentonite clay composite as a highly effective and low-cost adsorbent for the removal of doxycycline hydrochloride antibiotic and mercury ions in water.

Natural-occurring polymer intercalated inorganic clay composites have received increasing interests in water cleanup for the features of eco-friendliness, cost-effectiveness, and availability. Herein, a new lignin xanthate resin (LXR) intercalated bentonite clay composite (LXR-BT) for the adsorption of representative organic doxycycline hydrochloride (DCH) antibiotic and inorganic Hg(II) in water was created through a feasible process. Structural characterizations by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Thermo gravimetric analysis (TG), and scanning electron microscopy (SEM) confirmed LXR was successfully intercalated between the layers of bentonite clay. The adsorption performance of DCH/Hg(II) by LXR-BT was studied in detail with varied dosage, solution pH, contact time, and initial DCH/Hg(II) concentration. The results indicated that the adsorption capacities of DCH/Hg(II) on LXR-BT were much higher than that on bentonite, and the adsorption kinetics and isotherms followed the pseudo-second-order model and Langmuir model, respectively. X-ray photoelectron spectroscopy (XPS) analysis confirmed the adsorption mechanisms of DCH (or Hg(II)) was mainly due to π-π interaction and hydrogen bonding interaction of DCH (or the complexation of Hg(II)) with the functional groups in the LXR-BT. This study suggested the possibility of LXR-BT as a new cost-effective adsorbent for both organic and inorganic pollutants removal in water.

ß-Catenin phosphorylation at Y654 and Y142 is crucial for high mobility group box-1 protein-induced pulmonary vascular hyperpermeability.

OBJECTIVE: Endothelial hyperpermeability is a hallmark of acute lung injury in response to sepsis. The imbalance between adherence junction (AJ) mediated cell-cell adherence forces and stress fiber driven contractile forces contributes to increased endothelial permeability. Here, we spotlight the effects of ß-catenin Y654 andY142 phosphorylation on HMGB1-mediated endothelial barrier leakage. APPROACH AND RESULTS: Our results showed that phospho-deficiencies at both ß-catenin Y654and Y142ameliorated pulmonary vascular dysfunction in male C57 mice receiving a cecal ligation and puncture operation. In vitro analysis indicated that high mobility group box-1 protein (HMGB1) triggered ß-catenin Y654 and Y142 phosphorylation, causing ß-catenin translocation and adherence junction (AJ) disruptions as well as cytoskeleton rearrangement. In addition,ß-catenin Y654 dephosphorylation attenuated HMGB1-mediated dissociation of VE-cadherin/ß-catenin and, hence, partially prevented endothelial hyperpermeability. ß-catenin Y142 dephosphorylation abolished HMGB1-induced uncoupling of ß-catenin and α-catenin, suppressed cytoskeletal reassembly and, hence, alleviated endothelial hyperpermeability. Further investigation demonstrated that RAGE and Src were required forß-catenin Y654 phosphorylation in response to HMGB1, while FAK was responsible for HMGB1-triggered ß-catenin Y142 phosphorylation. CONCLUSIONS: In sum, this study revealed the role of ß-catenin Y654 and Y142 phosphorylation in HMGB1-mediated endothelial hyperpermeability through dysregulation between adherence and contractile forces. This result advances understanding of the mechanisms underlying pulmonary vascular hyperpermeability in sepsis.

Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promotes Thyroid Cancer Cell Proliferation and Migration via Ubiquitin-Dependent Degradation of Kisspeptin-1.

BACKGROUND/AIMS: Thyroid cancer is the most common malignancy in human endocrine system. Smad ubiquitination regulatory factor 1 (Smurf1) is an E3 ubiquitin-protein ligase in ubiquitin-proteasome pathway (UPP) system. This study aimed to investigate the effects of Smurf1 on thyroid cancer proliferation and metastasis, as well as underlying potential mechanism. METHODS: The expression levels of Smurf1 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of Smurf1 on thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were measured using trypan blue exclusion assay, two-chamber migration (invasion) assay, cell colony formation assay and Guava Nexin assay, respectively. The ubiquitination of kisspeptin-1 (KISS-1) was assessed by protein ubiquitination assay. Finally, the effects of KISS-1 overexpression on activity of nuclear factor-kappa B (NF-κB) signaling pathway, as well as thyroid cancer cell viability, migration, invasion, proliferation and apoptosis were also detected, respectively. RESULTS: Smurf1 was highly expressed in thyroid tumor tissues and thyroid cancer cells. Up-regulation of Smurf1 promoted the viability, migration, invasion and proliferation of thyroid cancer cells. Knockdown of Smurf1 had opposite effects. Moreover, smurf1 promoted the ubiquitination of KISS-1. Overexpression of KISS-1 inactivated NF-κB pathway, suppressed thyroid cancer cell viability, migration, invasion and proliferation, and induced cell apoptosis. CONCLUSION: Up-regulation of Smurf1 exerted important roles in thyroid cancer formation and development by promoting thyroid cancer proliferation and metastasis. The ubiquitin-dependent degradation of KISS-1 induced by Smurf1 and the activation of NF-κB signaling pathway might be involved in this process. Smurf1 could be an effective therapy target and biomarker for thyroid cancer treatment.

Src Plays an Important Role in AGE-Induced Endothelial Cell Proliferation, Migration, and Tubulogenesis.

Advanced glycation end products (AGEs), produced by the non-enzymatic glycation of proteins and lipids under hyperglycemia or oxidative stress conditions, has been implicated to be pivotal in the development of diabetic vascular complications, including diabetic retinopathy. We previously demonstrated that Src kinase played a causative role in AGE-induced hyper-permeability and barrier dysfunction in human umbilical vein endothelial cells (HUVECs). While the increase of vascular permeability is the early event of angiogenesis, the effect of Src in AGE-induced angiogenesis and the mechanism has not been completely revealed. Here, we investigated the impact of Src on AGE-induced HUVECs proliferation, migration, and tubulogenesis. Inhibition of Src with inhibitor PP2 or siRNA decreased AGE-induced migration and tubulogenesis of HUVECs. The inactivation of Src with pcDNA3/flag-SrcK298M also restrained AGE-induced HUVECs proliferation, migration, and tube formation, while the activation of Src with pcDNA3/flag-SrcY530F enhanced HUVECs angiogenesis alone and exacerbated AGE-induced angiogenesis. AGE-enhanced HUVECs angiogenesis in vitro was accompanied with the phosphorylation of ERK in HUVECs. The inhibition of ERK with its inhibitor PD98059 decreased AGE-induced HUVECs angiogenesis. Furthermore, the inhibition and silencing of Src suppressed the AGE-induced ERK activation. And the silencing of AGEs receptor (RAGE) inhibited the AGE-induced ERK activation and angiogenesis as well. In conclusions, this study demonstrated that Src plays a pivotal role in AGE-promoted HUVECs angiogenesis by phosphorylating ERK, and very likely through RAGE-Src-ERK pathway.

Study of the simulated sunlight photolysis mechanism of ketoprofen: the role of superoxide anion radicals, transformation byproducts, and ecotoxicity assessment.

The aim of this study was to investigate the photolysis mechanism of ketoprofen (KET) under simulated sunlight. The results demonstrated that the photolysis of KET aligned well with pseudo first-order kinetics. Radical scavenging experiments and dissolved oxygen experiments revealed that the superoxide anion radical (O2˙-) played a primary role in the photolytic process in pure water. Bicarbonate slightly increased the photodegradation of KET through generating carbonate radicals, while DOM inhibited the photolysis via both attenuating light and competing radicals. Moreover, Zhujiang river water inhibited KET phototransformation. Potential KET degradation pathways were proposed based on the identification of products using LC/MS/MS and GC/MS techniques. The theoretical prediction of reaction sites was derived from Frontier Electron Densities (FEDs), which primarily involved the KET decarboxylation reaction. The ecotoxicity of the treated solutions was evaluated by employing Daphnia magna and V. fischeri as biological indicators. Ecotoxicity was also hypothetically predicted through the "ecological structure-activity relationship" (ECOSAR) program, which revealed that toxic products might be generated during the photolysis process.

Glycosyltransferases and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized.

[Transcervical tongue partial reduction combined with uvulopalatopharyngoplasty in treatment of obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To treat severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with transcervical tongue partial reduction and evaluate treating effect. METHODS: Forty four patients of severe OSAHS were treated with transcervical tongue partial reduction + uvulopalatopharyngoplasty (UPPP). Apnea hypopnea index (AHI), minimal oxygen percent saturation, body mass index (BMI), area of retroglossal region were measured for diagnosis and evaluation. RESULTS: AHI decreased from (67.5 ± 21.1) times/h to (10.5 ± 6.8) times/h (t = 2.1, P < 0.01). The lowest oxygen percent saturation increased from 0.694 ± 0.009 to 0.829 ± 0.008 (t = 4.3, P < 0.01). The area of retroglossal region increased from (291.7 ± 107.8) mm² to (398.1 ± 94.5) mm² (t = 3.318, P < 0.05). Four patients complained dysphagia half year after operation. One patient complained about pharyngeal fistula, which disappeared in 2 weeks. One patient appeared hypoglossis bleeding, which stopped after compression. CONCLUSION: Transcervical tongue partial reduction is an effective attempt and supplement for OSAHS with retroglossal region narrow.

[Effect of TLR4 on the migration of asthmatic airway smooth muscle cells induced by airway epithelial cells].

OBJECTIVE: To explore the effect of Toll-like receptor 4 (TLR4) activation on the migration of asthmatic airway smooth muscle cell (ASMCs) induced by airway epithelial cells. METHODS: Primary ASMCs were cultured by the method of cell digestion. Cell culture supernatant of RTE cells were collected by TNF-alpha stimulation of epithelial cells. Detected the IL-8 and RANTES levels in the supernatant. The transmembrane migration of asthmatic ASMCs were detected by Modified Boyden chemotaxis chamber. The effect of TLR4 on the migration of asthmatic ASMCs induced by epithelial cells with TLR4 antibody drugs as a tool. RESULTS: The levels of IL-8 and RANTES in the supernatant of TNF-alpha groups were significantly increased, and that in the 20 ng/ml group was significantly higher than other groups (P < 0.01). The transmembrane migration of asthmatic ASMCs groups was increased than that of control group. The transmembrane migration of asthmatic ASMCs from asthma group and TNF-alpha + TLR4 antibody group was significantly decreased compared with that in TNF-alpha group (P < 0.01). The migration of asthma ASMCs from TNF-alpha + TLR4 antibody group was increased than that of asthma group (P < 0.05). CONCLUSION: TLR4 in the surface of asthmatic ASMCs may be activated by cytokines secreted by the airway epithelial cells and enhance the transmembrane migration of asthmatic ASMCs induced by airway epithelial cells so that it plays a role in airway remodeling of asthma.