Identification of immune-associated biomarker for predicting lung adenocarcinoma: bioinformatics analysis and experiment verification of PTK6.

BACKGROUND: Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. OBJECTIVE: The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. METHODS: The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. RESULTS: PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-ß signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. CONCLUSION: PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

In vitro corrosion resistance and dual antibacterial ability of curcumin loaded composite coatings on AZ31 alloy: Effect of amorphous calcium carbonate.

Rapid corrosion and bacterial infection are obstacles to put into use biodegradable magnesium (Mg) alloy as biomedical materials. In this research, an amorphous calcium carbonate (ACC)@curcumin (Cur) loaded poly-methyltrimethoxysilane (PMTMS) coating prepared by self-assembly method on micro-arc oxidation (MAO) coated Mg alloy has been proposed. Scanning electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy are adopted to analyze the morphology and composition of the obtained coatings. The corrosion behaviour of the coatings is estimated by hydrogen evolution and electrochemical tests. The spread plate method without or with 808 nm near-infrared irradiation is applied to evaluate the antimicrobial and photothermal antimicrobial ability of the coatings. Cytotoxicity of the samples is tested by 3-(4,5)-dimethylthiahiazo(-z-y1)-2,5-di- phenytetrazoliumromide (MTT) and live/dead assay culturing with MC3T3-E1 cells. Results show that the MAO/ACC@Cur-PMTMS coating exhibited favourable corrosion resistance, dual antibacterial ability, and good biocompatibility. Cur was employed as an antibacterial agent and photosensitizer for photothermal therapy. The core of ACC significantly improved the loading of Cur and the deposition of hydroxyapatite corrosion products during degradation, which greatly promoted the long-term corrosion resistance and antibacterial activity of Mg alloys as biomedical materials.

Corrosion resistance and mechanisms of Nd(NO3)3 and polyvinyl alcohol organic-inorganic hybrid material incorporated MAO coatings on AZ31 Mg alloy.

This work reports the design and preparation of novel organic (polyvinyl alcohol, PVA)-inorganic (neodymium nitrate, Nd(NO3)3) hybrid coatings on micro-arc oxidation (MAO) coating for magnesium (Mg) alloy corrosion protection. X-ray diffractometer, X-ray photoelectron spectroscopy, fourier transform infrared spectroscopy, field emission scanning electron microscope, Energy Dispersive X-ray spectrometer and surface roughness were applied to characterize the chemical composition and surface morphology of the coatings. The corrosion resistance of the coatings was evaluated by electrochemical and salt spray tests. The results suggested that the formation of PVA-Nd3+ and PVA-Mg2+ complexes promoted the enrichment of Nd3+ on the surface, and thereby improved the sealing quality and compactness of the coating. Interestingly, when the coating was damaged, the Nd3+ ions were transformed to their carbonates and covered the active sites, and thus exhibiting self-healing function. Further, the corrosion resistance of PVA-Nd3+ modified MAO composite coating on AZ31 Mg alloy was improved.

[Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine].

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine / 中国中药杂志

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Comparison of clinical and radiological characteristics in autoimmune GFAP astrocytopathy, MOGAD and AQP4-IgG+ NMOSD mimicking intracranial infection as the initial manifestation.

OBJECTIVE: Several autoimmune CNS inflammatory diseases, including autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSD) often presented initially with similar symptoms mimicking intracranial infection, are not easy to be differentiated during early-onset lacking the detection of autoantibody. METHODS: In our single-center cohorts, those patients mimicking intracranial infection as initial symptoms, including 9 with A-GFAP-A, 17 with MOGAD and 11 with AQP4-IgG+NMOSD, were retrospectively included. The autoantibodies were detected by cell-based assays. The clinical, immunological and radiological characteristics were summarized. RESULTS: In the cohort, tremor and positive Kernig's sign were predominated in A-GFAP-A (44.4% and 77.8%, respectively) over MOGAD (5.9%, p = 0.034; 29.4%, p = 0.038) and AQP4-IgG+NMOSD (0, p = 0.026; 18.2%, p = 0.022). Ten patients (A-GFAP-A, 4; MOGAD, 5; AQP4-IgG+NMOSD, 1) were initially misdiagnosed as tubercular or viral meningoencephalitis, however, resistant to empiric anti-tuberculosis or anti-viral treatment, and finally were in partial or complete remission with the immunotherapy when adjusted treatments. On cerebrospinal fluid (CSF) examination, white blood cell counts in CSF was higher in A-GFAP-A cohort (median, 90×106/L [IQR, 41-209]) compared to AQP4-IgG+ NMOSD (median, 6 × 106/L [IQR, 1-10], p = 0.018). Importantly, the higher increase in CSF protein (1319 mg/L [IQR, 1035-1519]), lactate dehydrogenase (LDH, 53.9 ± 37.2 U/L), lactic acid (3.50 ± 0.88 mmol/L), IgG (130.9 ± 60.4 mg/L), IgM (8.6 ± 6.1 mg/L) and IgA (23.0 ± 11.4 mg/L) levels in A-GFAP-A was found compared to MOGAD (CSF protein: 441 mg/L [IQR, 330-776], p = 0.004; LDH: 53.9  ±  37.2 U/L, p = 0.005; lactic acid: 2.15 ± 0.62 mmol/L, p = 0.001; IgG: 77.9 ± 71.3 mg/L, p = 0.018; IgM, 2.7 ± 2.9 mg/L, p = 0.015) and AQP4-IgG+ NMOSD (CSF protein: 386 mg/L [IQR, 369-453], p = 0.002; LDH: 23.7 ± 11.0 U/L, p = 0.048; lactic acid: 2.40  ±  0.66 mmol/L, p = 0.040; IgG, 53.2 ± 30.3 mg/L, p = 0.015; IgM, 2.1 ± 3.9 mg/L, p = 0.004; IgA, 5.2 ± 5.0 mg/L, p < 0.001). Of Note, smaller (< 2 cm), symmetrical lesions in ganglia and thalamus (5/8, 62.5%) were showed in over half of the A-GFAP-A patients (5/8, 62.5%), but never in MOGAD (0%, p = 0.001) and AQP4-IgG+NMOSD (0%, p = 0.026). In addition, diffuse meningeal enhancement was more common in A-GFAP-A (8, 88.9%) compared to MOGAD (5, 29.4%, p = 0.011) and AQP4-IgG+NMOSD (1/6, 16.7%, p = 0.011), respectively. Acute disseminated encephalomyelitis (ADEM) -like lesions occurred more frequently in MOGAD (6/16, 37.5%) but never in A-GFAP-A and AQP4-IgG+NMOSD (p = 0.02). CONCLUSION: Our study demonstrates that several distinct features including the symptom of tremor, higher CSF immunological profiles, bilateral symmetrical lesions in ganglia, and diffuse meningeal enhancement are frequent in A-GFAP-A, whereas ADEM-like lesions seem to occur mainly in MOGAD. These signs provide crucial clinical implications in differential diagnosis for those mimicking intracranial infection as initial symptoms. Clinicians should consider the possibility of these autoimmune CNS inflammatory diseases masquerading as intracranial infection.

In vitro degradation, photo-dynamic and thermal antibacterial activities of Cu-bearing chlorophyllin-induced Ca-P coating on magnesium alloy AZ31.

Surgical failures, caused by postoperative infections of bone implants, are commonly met, which cannot be treated precisely with intravenous antibiotics. Photothermal therapy (PTT) and photodynamic therapy (PDT) have attracted widespread attention due to their non-invasive antibacterial effects on tissues and no bacterial resistance, which may be an excellent approach to solve infections related to bone implants for biodegradable magnesium alloys. Herein, a sodium copper chlorophyllin (SCC) with a porphyrin ring induced Ca-P coating was prepared on AZ31 magnesium alloy via layer-by-layer (LbL) assembly. The morphology and composition of the samples were characterized through field emission scanning electron microscope (FE-SEM) with affiliated energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and Fourier infrared spectrometer (FTIR) and X-ray photoelectron spectrometer (XPS) as well. Potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and hydrogen evolution experiments were employed to evaluate the corrosion behavior of the samples. Atomic absorption spectrophotometer was used to measure Cu elemental content of different immersion periods. Cytocompatibility and antibacterial performance of the coatings were probed using in vitro cytotoxicity tests (MTT assay), live/dead cell staining and plate counting method. The results showed that the obtained (Ca-P/SCC)10 coating exhibited good corrosion resistance, antimicrobial activity (especially under 808 nm irradiation) and biocompatibility. The antibacterial rates for E. coli and S. aureus were 99.9% and 99.8%, respectively; and the photothermal conversion efficiency was as high as 42.1%. Triple antibacterial mechanisms including photodynamic, photothermal reactions and copper-ions release were proposed. This coating exhibited a promising application for biodegradable magnesium alloys.

Establishment of biological reference interval for reverse triiodothyronine by indirect method / 中华核医学与分子影像杂志

Objective:To establish reverse triiodothyronine (rT 3) biological reference interval suitable for laboratory by indirect method. Methods:From April to September 2019, 797 cases (332 males, 465 females, age: 12-95 years) underwent thyroid function, thyroid related antibody and rT 3 tests from hospitalized population in Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine were retrospectively analyzed. The reference individuals with normal thyroid hormone, antibody and without thyroid nodule or goiter were screened as inclusion criteria, and the factors such as acute and chronic diseases or drugs that might affect the values of rT 3 were excluded. Independent sample t test, one-way analysis of variance and least significant difference t test were used to analyze data. The rT 3 reference interval was established by non-parametric sequencing method, and 2.5% and 97.5% percentile values of data distribution were selected as the upper and the lower reference limits. In order to verify the rT 3 reference interval, 20 healthy individuals and 20 inpatients who met the inclusion and exclusion criteria were selected to test rT 3 with a simple random sampling method. Results:A total of 159 reference individuals (66 males, 93 females, age: 23-87 years) were enrolled. The rT 3 values of 23-29( n=4), 30-39( n=18), 40-49( n=29), 50-59( n=43), 60-69( n=40), 70-79( n=19) and over 80( n=6) years old groups were (0.62±0.16), (0.63±0.12), (0.64±0.11), (0.61±0.11), (0.65±0.14), (0.65±0.11) and (0.79±0.10) μg/L, respectively. There was a statistically significant difference in the rT 3 test results among different age groups ( F=2.17, P=0.049). There were statistically significant differences of rT 3 between the individuals over 80 years old and other age groups (all P<0.05), while there were no statistically significant differences among the other groups (all P>0.05). The rT 3 of males and females under 80 years old were (0.62±0.11) and (0.64±0.12) μg/L, respectively, with no significant difference between them ( t=-0.81, P=0.420). The newly established rT 3 reference interval suitable for people above 20 years old and below 80 years old was 0.47-0.92 μg/L, and the lower limit was significantly higher than that of the reference interval in the reagent specification (0.20-0.95 μg/L). The rT 3 range of 20 healthy individuals was 0.57-0.82 μg/L and that of 20 inpatients was 0.48-0.77 μg/L, which were all within the new reference interval. Conclusion:The rT 3 biological reference interval established here has clinical application value, but its applicable range of age still needs to be further improved.

Sphingosine-1-Phosphate Signaling in Ischemic Stroke: From Bench to Bedside and Beyond.

Sphingosine-1-phosphate (S1P) signaling is being increasingly recognized as a strong modulator of immune cell migration and endothelial function. Fingolimod and other S1P modulators in ischemic stroke treatment have shown promise in emerging experimental models and small-scale clinical trials. In this article, we will review the current knowledge of the role of S1P signaling in brain ischemia from the aspects of inflammation and immune interventions, sustaining endothelial functions, regulation of blood-brain barrier integrity, and functional recovery. We will then discuss the current and future therapeutic perspectives of targeting S1P for the treatment of ischemic stroke. Mechanism studies would help to bridge the gap between preclinical studies and clinical practice. Future success of bench-to-bedside translation shall be based on in depth understanding of S1P signaling during stroke and on the ability to have a fine temporal and spatial regulation of the signal pathway.

Optical planar and ridge waveguides formed in Er3+-doped germanate glass by ion implantation and precise diamond blade dicing.

In this work, we report on the preparation and characterization of the planar and ridge optical waveguides in the Er3+-doped germanate glass by combining hydrogen ion implantation and precise diamond blade dicing. The nuclear energy loss and the implantation depth were calculated by the SRIM 2013 software. The refractive index profile was obtained by the reflectivity calculation method. The dark-mode spectrum and the near-field intensity distribution were measured by the prism coupling system and end-face coupling technique, respectively. This work has important reference significance for the development of Er3+-doped germanate glass active devices in the optical communication field.

Predictive Factors of Resistance to High-Dose Steroids Therapy in Acute Attacks of Neuromyelitis Optica Spectrum Disorder.

High-dose steroids, the first-line therapy for acute attacks in neuromyelitis optica spectrum disorder (NMOSD), were ineffective in a proportion of NMOSD attacks. This study aimed to explore possible predictors of high-dose steroid resistance. Demographics and disease characteristics of acute attacks were compared between those who responded to high-dose intravenous methylprednisolone (IVMP) and those resistant to IVMP. In total, 197 attacks in 160 patients were identified in our NMOSD registry. Compared with responders, attacks resistant to high-dose steroids tended to have a higher proportion of previous history of immunosuppressive use (25.5 vs. 15.5%, p = 0.080). Significantly higher levels of proteins in the cerebrospinal fluid (CSF) were found in non-responders than in responders [485.5 (388-656) vs. 387 (291.5-532) mg/L, p = 0.006]. More active lesions were found in the brain stem of non-responders (8 attacks in 55, 14.5%), especially in the pons (7.3%) and medulla (14.5%), as opposed to responders (7 patients in 142, 4.9%). Multivariable logistic regression showed that resistance to high-dose steroid treatment was associated with previous immunosuppressant use [odds ratio (OR), 2.31; 95% confidence interval (CI) 1.002-5.34, p = 0.049], CSF protein level above 450 mg/L (OR 3.42, 95% CI 1.72-6.82, p < 0.001), and active lesions in the brainstem (OR 3.80, 95% CI 1.17-12.32, p = 0.026). In conclusion, NMOSD patients with previous use of immunosuppressants, higher levels of CSF protein, and active lesions in the brainstem are more likely to respond poorly to high-dose IVMP alone during an acute attack.

Efficacy of plasma exchange in acute attacks of neuromyelitis optica spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Plasma exchange (PE) has usually to be considered as a rescue therapy when intravenous corticosteroids is insufficient in acute attacks of neuromyelitis optica spectrum disorders (NMOSD). The efficacy of PE has not been quantified. This system review and meta-analysis was aimed to evaluate the efficacy of PE therapy in acute attacks of NMOSD. METHODS: Studies evaluating the efficacy of PE in patients with NMOSD were identified from PubMed and Embase. Changes of Expanded Disability Status Scale (EDSS) score between before and after PE therapy, and the rate of response to PE, were defined as the main efficacy outcomes. Meta-regression was performed to identify the sources of heterogeneity. Subgroup meta-analysis were performed based on the interval of initiation PE after attack onset and AQP4-IgG serostatus of patients. RESULTS: Twenty-four studies containing 528 patients with NMOSD were included in this meta-analysis. As a rescue therapy when patients failed to respond to intravenous corticosteroids (PE rescue), PE treatment resulted in a reduction in the mean EDSS score by 1.69 (95% CI: 0.88-2.50), with a response rate of 75%(95%CI: 66%-83%). As a first-line therapy being used alone or simultaneously with intravenous corticosteroids (PE first-line), PE resulted in a reduction in the mean EDSS score by 2.34 (95% CI: 1.69-2.98), with a response rate of 71%(95%CI: 44%-93%). Overall, PE resulted in a reduction in the mean EDSS score by 1.83 (95% CI: 1.19-2.47), with a response rate of 74% (95%CI: 66%-82%). Subgroup analysis suggested that earlier PE initiation and AQP4-IgG seronegative patients seemed to be associated with a superior response to PE therapy. CONCLUSION: Plasma exchange, whether used as rescue or as first-line therapy, is an effective therapeutic method in patients during acute attacks of NMOSD.

An Unprecedented Ring-Contraction Mechanism in Cobalamin-Dependent Radical S-Adenosylmethionine Enzymes.

A unique member of the family of cobalamin (Cbl)-dependent radical S-adenosylmethionine (SAM) enzymes, OxsB, catalyzes the ring constriction of deoxyadenosine triphosphate (dATP) to the base oxetane aldehyde phosphate, a crucial precursor for oxetanocin A (OXT-A), which is an antitumor, antiviral, and antibacterial compound. This enzyme reveals a new catalytic function for this big family that is different from the common methylation. On the basis of density functional theory calculations, a mechanism has been proposed to mainly include that the generation of 5'-deoxyadenosine radical, a hydrogen transfer forming 2'-dATP radical, and a Cbl-catalyzed ring contraction of the deoxyribose in 2'-dATP radical. The ring contraction is a concerted rearrangement step accompanied by an electron transfer from the deoxyribose hydroxyl oxygen to CoIII without any ring-opening intermediate. CoIICbl has been ruled out as an active state. Other mechanistic characteristics are also revealed. This unprecedented non-methylation mechanism provides a new catalytic repertoire for the family of radical SAM enzymes, representing a new class of ring-contraction enzymes.

In vitro corrosion resistance of layer-by-layer assembled polyacrylic acid multilayers induced Ca-P coating on magnesium alloy AZ31.

Biodegradable magnesium (Mg)-based alloys have aroused great concern owing to their promising characteristics as temporary implants for orthopedic application. But their undesirably rapid corrosion rate under physiological conditions has limited the actual clinical application. This study reports the use of a novel biomimetic polyelectrolyte multilayer template, based on polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) via layer-by-layer (LbL) assembly, to improve the corrosion resistance of the alloy. Surface characterization techniques (field-emission scanning electron microscopy, Fourier transform infrared (FTIR) spectrophotometer and X-ray diffractometer) confirmed the formation of biomineralized Ca-P coating on AZ31 alloy. Both hydrogen evolution and electrochemical corrosion tests demonstrated that the corrosion protection of the polyelectrolyte-induced Ca-P coating on AZ31 alloy. The formation mechanism of biomineralized Ca-P coating was proposed.

Application of 3D visualization and 3D printing in individualized precision surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma / 南方医科大学学报

OBJECTIVE@#To explore the application of 3D visualization and 3D printing in individualized precision surgical treatment of Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma.@*METHODS@#We retrospectively analyzed the data of 10 patients with hilar cholangiocarcinoma undergoing surgeries under the guidance of 3D visualization and 3D printing in the Department of Hepatobiliary Surgery, Zhujiang Hospital from May 2016 to March 2019. Thin-section CT data of the patients were collected for 3D reconstruction and 3D printing, and the 3D printed models were used for observing the 3D relationship of tumor with the intrahepatic bile duct, hepatic artery, portal vein and hepatic vein system and for performing preoperative simulated surgery and surgical planning. The 3D printed models were subsequently used for real-time intraoperative navigation to guide surgeries in the operating room.@*RESULTS@#3D visualization models were successfully reconstructed for all the 10 patients and printed into 3D models. The 3D visualization types in Bismuth-Corlette classification included type Ⅲa (4 cases), type Ⅲb (4 cases), and type Ⅳ (2 cases); 4 patients showed portal vein variation, 3 had hepatic artery variation, and 2 had both portal vein and hepatic artery variations. Two patients were found to have trifurcation type of portal vein variation, one had "I-shaped" variation, and one showed the absence of the right anterior branch of the portal vein; 3 patients had hepatic artery variations with the left hepatic artery originating from the left gastric artery (1 case) and the right hepatic artery originating from the superior mesenteric artery (2 cases). Four patients with type Ⅲb underwent left hepatectomy; 4 with type Ⅲa received right hepatectomy; 1 patient with of type Ⅳ received peripheral hepatic resection and another underwent left hepatectomy. The results of preoperative 3D reconstruction, 3D printed model and preoperative planning were consistent with the intraoperative findings. The operative time was 452±75.12 min with a mean intraoperative blood loss of 356±62.35 mL and a mean hospital stay of 15 ± 4.61 days in these cases. One patient had bile leakage and 3 patients had pleural effusion postoperatively, and they were discharged after drainage and medications. No liver failure or death occurred in these cases perioperatively.@*CONCLUSIONS@#3D visualization and 3D printing can facilitate accurate preoperative assessment, surgical planning and surgical procedure optimization for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma to improve surgical safety and reduce surgical risks especially in cases of intrahepatic vascular variations.

In vitro corrosion of pure Mg in phosphate buffer solution-Influences of isoelectric point and molecular structure of amino acids.

Influences of proteins on degradation of magnesium alloys are of great significance but not well understood. In particular the roles of amino acids, the basic unit of proteins in regulating the progress of biodegradation of magnesium based materials remain unclear. This study aims to investigate the impacts of alanine, glutamic acid and lysine on degradation of pure magnesium in phosphate buffer solution through SEM, XPS, FTIR, potentiodynamic polarisation curves, electrochemical impedance spectroscopy and immersion tests. The changed contents of amino acids in solutions were detected by UV-vis spectrophotometer. Results demonstrate that the charges of the selected amino acids imposed significant contribution to suppressing the degradation of pure magnesium in phosphate buffer solution. The presence of amino acids led to the formation of phosphate-based corrosion products, increasing free corrosion potential, and reduction in corrosion current density and solution pH depending on their isoelectric points and molecular structures. A plausible corrosion mechanism organised by amino acids on pure magnesium was proposed.

Autophagy inhibition exerts neuroprotection on white matter ischemic damage after chronic cerebral hypoperfusion in mice.

Autophagy plays vital roles in the pathophysiology of many central nervous system diseases. Emerging evidence indicates that autophagy has both detrimental and protective effects in ischemic cerebral injury. This study aimed to investigate the temporal pattern of autophagy activation in the white matter of bilateral common carotid artery stenosis (BCAS) mouse model by immunofluorescence and western blotting. The effect of wortmannin, an autophagy inhibitor, against hypoperfusion induced white matter injury (WMI) was studied by immunofluorescence and eight-arm radial maze test. We found that autophagy was initially activated in the white matter 3 days after BCAS, and then suppressed by day 10, and was activated again at day 30. Administration of wortmannin during the first three days after BCAS revealed protective effects on axon-glia integrity and against the cognitive injury induced by the chronic hypoperfusion. The results indicated the possible link between autophagy and white matter ischemic damage after chronic cerebral hypoperfusion. Modulation of autophagy in a time course dependent manner may broaden the insight on the treatment of WMI.

How does Mo-dependent perchlorate reductase work in the decomposition of oxyanions?

Mo-Dependent perchlorate reductase (PcrAB), responsible for the ending step of anaerobic respiration of perchlorate reducing bacteria, catalyzes the conversion of perchlorate to chlorate and subsequently chlorite and is also able to deoxidate bromate, iodate, and nitrate. Herein, the reaction mechanisms for the PcrAB-catalyzed decomposition of these oxyanions have been investigated using density functional calculations and a chemical model constructed from the X-ray crystal structure. It is revealed that the reactions of halogen oxyanions proceed through a very fast O-X (X = Cl, Br, and I) heterolytic cleavage activated by the MoIV center, followed by a rate-limiting reduction of the resulting MoVI[double bond, length as m-dash]O back to MoIV dominated by the slow proton-coupled electron transfer (PCET). However, the O-N bond heterolysis in the nitrate decomposition has a barrier (16.2 kcal mol-1) comparable to the PCET-dominating reduction of MoVI[double bond, length as m-dash]O. This heralds an exciting future where a proper mutation of electron/proton transfer passage of perchlorate reducing bacteria may lead to a decomposition preference for halogen oxyanions rather than non-toxic nitrate, providing a friendly bioremediation method. Other open mechanistic questions are also addressed, where in particular an O-O rebound mechanism without PCET has been ruled out.

Corrosion resistance and antibacterial properties of hydroxyapatite coating induced by gentamicin-loaded polymeric multilayers on magnesium alloys.

As a result of their good biocompatibility, bioactivity, and mechanical properties, magnesium (Mg) alloys have received considerable attention as next generation biodegradable implants. Herein, in order to achieve a proper degradation rate and good antibacterial ability, we reported a novel hydroxyapatite coating induced by gentamicin (GS)-loaded polymeric multilayers for the surface treatment of the Mg alloy. The coating was characterized by X-ray diffraction, fourier transform infrared spectroscopy and scanning electron microscopy. The as-prepared hydroxyapatite coating showed the compact morphology and a well-crystallized apatite structure. This coating could improve the adhesion strength and reduce the corrosion rate of the substrate in simulated body fluid solution. Meanwhile, the drug release and antibacterial experiments demonstrated that the GS loaded specimen revealed a significant antimicrobial performance toward Staphylococcus aureus and had a prolonged release profile of GS, which would be helpful to the long-term bactericidal activity of the Mg implant. This coating showed acceptable biocompatibility via MTT assay and Live/dead staining. Thus, the multilayers-hydroxyapatite coated Mg alloy could improve the corrosion resistance and biocompatibility while delivering vital drugs to the site of implantation.

Advances in functionalized polymer coatings on biodegradable magnesium alloys - A review.

Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and excellent biomechanical compatibility. However, their high degradation rate in the physiological environment should be well tackled prior to clinical applications. This review summarizes the latest progress in the development of polymeric coatings on biodegradable Mg alloys over the last decade, regarding preparation strategies for polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), polydopamine (PDA), chitosan (CS), collagen (Col) and their composite, and their performance in terms of corrosion resistance and biocompatibility. Feasible perspectives and developing directions of next generation of polymeric coatings with respect to biomedical Mg alloys are briefly discussed. STATEMENT OF SIGNIFICANCE: Magnesium (Mg) and its alloys have become a research frontier in biodegradable materials owing to their superior biocompatibility and suitable biomechanical compatibility. However, the principal drawback of Mg-based implants is their poor corrosion resistance in physiological environments. Hence, it is vital to mitigate the degradation/corrosion behavior of Mg alloys for safe biomedical deployments. This review summarizes the latest progress in development of polymeric coatings on biomedical Mg alloys regarding preparation strategy, corrosion resistance and biocompatibility, including polylactic acid (PLA), poly (latic-co-glycolic) acid (PLGA), polycaprolactone (PCL), chitosan (CS), polydopamine (PDA), collagen (Col) and their composite. In addition, functionalized polymer coatings with Mg alloys exhibits a promising prospect owing to their ability of degradation along with biocompatibility, self-healing, drug-delivery and osteoinduction.