Abstract Scutellarin, a flavonoid compound found in Scutellaria barbata, has been demonstrated to exert anti-cancer properity in a variety of human malignancies. However, its biological significance and underlying mechanism in glioblastoma (GBM) remain ambiguous. Network pharmacology approaches and molecular docking technologies were used to predict the crucial biological processes, candidate targets and signaling pathways of scutellarin against GBM. CCK-8, EdU, and colony formation experiments were performed to determine the effects of scutellarin on cell proliferation. Flow cytometry analysis was utilized to detect apoptosis. Western blot assays were used to measure the expression of proteins associated with EGFR-PI3K-AKT signaling. Through network pharmacology and molecular docking analysis, we found that EGFR might be a potential target and PI3K-AKT signaling might be the key signaling pathway for scutellarin to combat GBM. Scutellarin inhibited cell proliferation and induced apoptosis in a dose-dependent manner. Scutellarin also suppressed the phosphorylation level of EGFR in a dose-dependent manner. Scutellarin inactivated PI3K-AKT signaling by targeting EGFR. Moreover, scutellarin-mediated suppression of cell proliferation and increase of apoptosis was greatly reversed in GBM after overexpressing EGFR. Taken together, scutellarin is a novel inhibitor of EGFR-PI3K-AKT signaling to prevent GBM progression.

Abstract To investigate the effect of DNMT3A in vascular calcification (VC) induced by high phosphorus. The arterial tissues of 12 patients with end stage renal disease (ESRD) and VC and 12 patients with ESRD without VC were collected. Rat vascular smooth muscle cells (VSMCs) were divided into control group, high phosphorus (P) group, P + DMSO group, p-ERK1/2 inhibitor group, DNMT3A group and DNMT3A + P group and P + shRNA-DNMT3A group. Vascular calcification was evaluated by von kossa staining. Cell calcification was evaluated by alizarin red staining. The calcium content was assessed by calcium determination kit. The levels of DNMT3A, Runx2, LC3 and p-ERK1/2 were significantly up-regulated in CKD patients with VC in comparison with those in CKD patients without VC(p<0.05). Moreover, the levels of SM22α and P62 were notably decreased in CKD patients with VC in comparison with those in CKD patients without VC(p<0.05). Similar changes were observed in VSMCs induced by high phosphorus. Knock down of DNMT3A in VSMCs inhibited phenotypic transformation and induced autophagy, then reduced calcification(p<0.05). Moreover, p-ERK1/2 level was downregulated by knock down of DNMT3A in comparison with the control group(p<0.05). In conclusion, DNMT3A regulated high phosphorus induced vascular medial calcification via ERK1/2 signaling.

Abstract Character strengths could effectively prevent negative psychological outcomes in adults. However, there was little research conducted among early adolescents. The present study aimed to explore character strengths that were independently related to fewer behavior problems in early adolescents. In total, 521 early adolescents (mean age 10.92 ± 0.04, range 10–12 years) were recruited from primary schools in Sichuan, China. Character strengths were measured using the Values in Action Inventory of Strengths for Youth (VIA-Youth). Behavior problems were measured using the Conners Parent Symptom Questionnaire (PSQ). The results showed that behavior problems were negatively correlated with character strengths ( r = −0.14 to −0.3, p < 0.05 Bonferroni corrected). Character strengths explained a significant proportion of additional variance (14–22%) in five types of behavior problems after controlling the effect of demographic factors (residence, left-behind experiences, maternal education level). Moreover, several specific character strengths showed an independent contribution ( β = −0.34 to −0.14 for self-regulation, perseverance, zest, humility, and leadership; β = 0.21 to 0.34, for hope; all p < 0.05) to behavior problems. Our study revealed that character strengths were protective factors against behavior problems in early adolescents.

Stereotactic biopsies for lesions in the brainstem and deep brain are rare. This study aimed to summarize our 6-year experience in the accurate diagnosis of lesions in the brain stem and deep brain and to discuss the technical note and strategies. From December 2011 to January 2018, 72 cases of intracranial lesions in the brainstem or deep in the lobes undergoing stereotactic biopsy were retrospectively reviewed. An individualized puncture path was designed based on the lesion's location and the image characteristics. The most common biopsy targets were deep in the lobes (43 cases, 59.7%), including frontal lobe (33 cases, 45.8%), temporal lobe (4 cases, 5.6%), parietal lobe (3 cases, 4.2%), and occipital lobe (3 cases, 4.2 %). There were 12 cases (16.7%) of the brainstem, including 8 cases (11.1%) of midbrain, and 4 cases (5.6%) of pons or brachium pontis. Other targets included internal capsule (2 cases, 2.8%), thalamus (3 cases, 4.2%), and basal ganglion (12 cases, 16.7%). As for complications, one patient developed acute intracerebral hemorrhage in the biopsy area at 2 h post-operation, and one patient had delayed intracerebral hemorrhage at 7 days post-operation. The remaining patients recovered well after surgery. There was no surgery-related death. The CT-MRI-guided stereotactic biopsy of lesions in the brainstem or deep in the brain has the advantages of high safety, accurate diagnosis, and low incidence of complications. It plays a crucial role in the diagnosis of atypical, microscopic, diffuse, multiple, and refractory lesions.

Abstract Ti/Al/Mg/Al/Ti laminated composites were fabricated via hot-pressing at 350 °C, 400 °C and 450 °C successfully. The influences of interface morphology, diffusion zone, constraint effect on the mechanical properties were investigated. At Ti/Al interface, intermetallic compounds aren’t found. Whereas, they form at Al/Mg interface. With the increasing temperature, the bonding strength of Al/Mg interface doesn’t change linearly, and the maximum strength is obtained at 400 °C because of intermetallic compounds with appropriate thickness. With the increase of temperature, the hardness at both Ti/Al and Al/Mg interfaces increases owing to the solid solution and the intermetallic phases. Also, the ultimate tensile strength of LMCs increases with sacrificing the fracture elongation. The rule of mixture is used to predict the theoretical strength. It is found that the theoretical values are less than the measured, and the reasons may relate to interfaces in Ti/Al/Mg/Al/Ti laminated composites.

The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.

SUMMARY OBJECTIVES To evaluate the epidemiological characteristics of acute pancreatitis (AP) and explore potential relationships between these factors and severity. METHODOLOGY Data-sets of 5,659 patients with AP from health statistics and the Information Center of Jiangsu province, between 2014 and 2016, were analyzed. A self-organizing map (SOM) neural network was used for data clustering. RESULTS Biliary acute pancreatitis (BAP) (86.7%) was the most frequent etiological factor. A total of 804 (14.2%) patients had severe acute pancreatitis (SAP). The mean age of patients was 53.7 + 17.3 (range 12~94y). Most of the AP patients were married (75.4%); 6% of mild /moderately severe AP (MAP/MASP) patients were unmarried, which was less than SAP patients (P=0.016). AP patients with blood type AB in the general population (8.8%) was significantly lower than that of AP cases (13.9%) (P=0.019) and SAP cases(18.7%) (P=0.007). The number of AP patients in southern Jiangsu was much higher than that in northern Jiangsu province, especially in Nanjing (1229, 21.7%). The proportion of acute alcoholic pancreatitis (AAP) in the north of Jiangsu (Xuzhou 18.4%) was much higher than that in southern Jiangsu (Suzhou 2.6%). The whole sample was divided into five classes by SOM neural network. If BAP patients were male, old, divorced, and blood type AB or B, they were more likely to develop SAP. Middle-age, unmarried or divorced male patients with blood type B/AB who suffered from HAP or AAP were also more likely to develop SAP. CONCLUSIONS The number of unmarried patients with MAP/MASP was smaller than that of SAP. Blood types AB and B were more frequent in AP, especially in SAP. The differences between southern Jiangsu and northern Jiangsu, in number of AP patients and the proportion of AAP, were significant. In class I and class IV, the ratio of SAP was much higher than in other classes and the whole sample.

Abstract Negative Poisson’s ratio (NPR) material attracts a lot of attentions for its unique mechanical properties. However, achieving NPR is at the expense of reducing Young’s modulus. It has been observed that the composite stiffness can be enhanced when blending positive Poisson’s ratio (PPR) material into NPR material. Based on the respective interpolation of Young’s modulus and Poisson’s ratio, two concurrent topology optimization problems with different types of constraints, called Problem A and B, are respectively discussed to explore the Poisson’s ratio effect in porous microstructure. In Problem A, the volume constraints are respectively imposed on macro and micro structures; in Problem B, besides setting an upper bound on the total available base materials, the micro thermal insulation capability is considered as well. Besides considering the influence of micro thermal insulation capability on the optimized results in Problem B, the similar and dissimilar influences of Poisson’s ratios, volume fractions in Problem A and B are also investigated through several 2D and 3D numerical examples. It is observed that the concurrent structural stiffness resulting from the mixture of PPR and NPR base materials can exceed the concurrent structural stiffness composed of any individual base material.

Abstract Klebsiella pneumoniae is important human and animal pathogen that causes a wide spectrum of infections. In this study, isolates from cattle nasal swabs samples were identified by 16S rRNA, and to evaluate the antimicrobial susceptibility, virulence gene carrying levels, and multilocus sequence typing of K. pneumoniae isolates. 33 isolates of K. pneumoniae were isolated and identified in 213 nasal swabs samples, of which 12 were hypervirulent K. pneumoniae strains. Extended Spectrum Beta-Lactamases genes were found in 93.4% of the strains. Of which, TEM was the most prevalent (93.4%), followed by CTX-M and SHV were 57.6% and 39.4%, respectively. A main mutation pattern of quinoloneresistance-determining region, Thr83-Ieu and Asp87-Asn in gyrA and Ser87-Ile in parC, was detected in 33 K. pneumoniae isolates. All the isolates harbored at least two virulence factor genes, with ureA (97.0%) and wabG (91.0%) exhibiting high carriage rates in 33 K. pneumoniae isolates. MLST revealed 7 sequence types, of which 3 STs (2541, 2581 and 2844) were newly assigned. Using eBURST, ST2844 and ST2541 were assigned to new clonal complex 2844. Our study provides evidence and biological characteristics of K. pneumoniae isolates from cattle upper respiratory tract in Southwest China.

Abstract The aerobic degradation of aromatic compounds by bacteria is performed by dioxygenases. To show some characteristic patterns of the dioxygenase genotype and its degradation specificities, twenty-nine gram-negative bacterial cultures were obtained from sediment contaminated with phenolic compounds in Wuhan, China. The isolates were phylogenetically diverse and belonged to 10 genera. All 29 gram-negative bacteria were able to utilize phenol, m-dihydroxybenzene and 2-hydroxybenzoic acid as the sole carbon sources, and members of the three primary genera Pseudomonas, Acinetobacter and Alcaligenes were able to grow in the presence of multiple monoaromatic compounds. PCR and DNA sequence analysis were used to detect dioxygenase genes coding for catechol 1,2-dioxygenase, catechol 2,3-dioxygenase and protocatechuate 3,4-dioxygenase. The results showed that there are 4 genotypes; most strains are either PNP (catechol 1,2-dioxygenase gene is positive, catechol 2,3-dioxygenase gene is negative, protocatechuate 3,4-dioxygenase gene is positive) or PNN (catechol 1,2-dioxygenase gene is positive, catechol 2,3-dioxygenase gene is negative, protocatechuate 3,4-dioxygenase gene is negative). The strains with two dioxygenase genes can usually grow on many more aromatic compounds than strains with one dioxygenase gene. Degradation experiments using a mixed culture representing four bacterial genotypes resulted in the rapid degradation of phenol. Determinations of substrate utilization and phenol degradation revealed their affiliations through dioxygenase genotype data.

Abstract: Introduction and aim. Hyponatremia is common in patients with decompensated cirrhosis and is associated with increased mortality. Tolvaptan, a vasopressor V2 receptor antagonist, can increase free wáter excretion, but its efficacy and safety in cirrhotic patients remain unclear. Material and methods. We studied the usage and safety of tolvaptan in cirrhotic patients in a real-life, non-randomized, multicenter prospective cohort study. Forty-nine cirrhotic patients with hyponatremia were treated with tolvaptan 15 mg daily, and 48 patients not treated with tolvaptan in the same period served as controls. Improvement in serum sodium level was defined as an increase in serum sodium from < 125 to ≥ 125 mmol/L or from 125-134 to ≥ 135 mmol/L on day 7. Results. Twenty-three (47%) patients in the tolvaptan group and 17 (35%) in the control group had normal serum sodium on day 7 (p = 0.25). Serum sodium improved in 30 (61%) patients in the tolvaptan group and 17 (35%) patients in the control group (p = 0.011). Adverse events occurred in 46-47% of patients in both groups, and tolvaptan was not associated with worsened liver function. No patient with normal serum sodium on day 7 died within 30 days of treatment, whereas 16% of those with persistent hyponatremia died (p = 0.0019). Conclusion. In conclusion, short-term tolvaptan treatment is safe and can improve serum sodium level in cirrhotic patients with hyponatremia. Normalization of serum sodium level is associated with better survival.

Abstract The dechlorination efficiency of zinc oxide dust using microwave roasting was investigated capitalizing on the different microwave absorbing capacities of the compounds such as chlorine, lead, and zinc oxide. The associated dechlorination reactions were discussed in detail and the effect of all the influencing parameters such as the air flow rate, steam flow rate, the roasting temperature, roasting duration, and the mixing rate were assessed to identify the optimal conditions. The results indicated that a near 93% dechlorination of zinc oxide dust could be achieved, which would satisfy the requirements of the wet smelting electrolysis process. The optimal process parameters were identified to be an air flow of 300 L/h, a steam flow of 8 mL/min, a stirring speed of 60 rpm, a roasting temperature of 650 ºC, and a roasting duration of 60 min. Water vapor has an enhanced effect on dechlorination by microwave roasting.

Two centrosymmetric mononuclear nickel(II) and zinc(II) complexes, [NiL2]-2NO3 (1) and [ZnL2(dca)2] (2), where L is the zwitterionic form of 2-bromo-6-[(3-cyclohexylaminopropylimino)methyl]phenol, and dca is the dicyanamide anion, have been synthesized. The complexes have been characterized by physico-chemical methods and single crystal X-ray determination. Complex (1) crystallizes in the monoclinic space group P2Jn with unit cell dimensions a = 7.0091(7) Å, b = 11.137(1) Å, c = 23.997(2) Å, β = 97.390(3)°, V = 1857.7(3) ų, Z = 2, R1 = 0.0617, and wR2 = 0.1632. Complex (2) crystallizes in the triclinic space group P-1 with unit cell dimensions a = 8.762(1) Å, b = 10.386(1) Å, c = 10.687(2) Å, α = 85.209(2)°, β = 83.931(2)°, g = 88.734(2)°, V = 963.6(2) ų, Z = 1, R1 = 0.0374, and wR2 = 0.0873. The Ni atom in (1) is in a square planar geometry, and the Zn atom in (2) is in an octahedral geometry. The preliminary antibacterial activities of the complexes were assayed.

摘要 目的 评估抗逆转录病毒治疗（ART）早期进行磺胺甲基异恶唑预防疗法是否降低中国艾滋病病毒（HIV）感染成年人的死亡率。 方法 我们使用中国国家免费抗逆转录病毒数据库的数据进行回顾性观察性队列研究。对14岁以上在2010年1月1日至2012年12月31日之间开始ART治疗并且基...

Résumé Objectif Évaluer si la prophylaxie par le cotrimoxazole administrée précocement au cours de la thérapie antirétrovirale (TAR) réduit la mortalité chez les adultes infectés par le virus de l'immunodéficience humaine (VIH) en Chine. Méthodes Nous avons effectué une étude de cohorte par observation rétrospective en utilisant les données de la base de données antirétrovirale gratuite nationale chinoise. Les patients âgés de plus de 14 ans qui ont commencé une TAR entre le 1er janvier 2010 et le 31 décembre 2012 et qui avaient un nombre de lymphocytes T CD4+ (cellules CD4+) à la ligne de base inférieur à 200 cellules/µL, ont été suivis jusqu'à leur décès, jusqu'à ce qu'ils soient perdus de vue au suivi ou jusqu'au 31 ...

Резюме Цель Определить, приводит ли профилактика котримоксазолом на раннем этапе антиретровирусной терапии (АРТ) к снижению смертности среди ВИЧ-инфицирова...

Objective To assess if cotrimoxazole prophylaxis administered early during antiretroviral therapy (ART) reduces mortality in Chinese adults who are infected with human immunodeficiency virus (HIV). Methods We did a retrospective observational cohort study using data from the Chinese national free antiretroviral database. Patients older than 14 years who started ART between 1 January 2010 and 31 December 2012 and had baseline CD4+ T-lymphocyte (CD4+ cell) count less than 200 cells/µL were followed until death, loss to follow-up or 31 December 2013. Hazard ratios (HRs) for several variables were calculated using multivariate analyses. Findings The analysis involved 23 816 HIV-infected patients, 2706 of whom died during the follow-up. Mortality in patients who did and did not start cotrimoxazole during the first 6 months of ART was 5.3 and 7.0 per 100 person–years, respectively. Cotrimoxazole was associated with a 37% reduction in mortality (hazard ratio, HR: 0.63; 95% confidence interval, CI: 0.56–0.70). Cotrimoxazole in addition to ART reduced mortality significantly over follow-up lasting 6 months (HR: 0.65; 95% CI: 0.59–0.73), 12 months (HR: 0.58; 95% CI: 0.49–0.70), 18 months (HR: 0.49; 95% CI: 0.38–0.63) and 24 months (HR: 0.66; 95% CI: 0.48–0.90). The mortality reduction was evident in patients with baseline CD4+ cell counts less than 50 cells/µL (HR: 0.60; 95% CI: 0.54–0.67), 50–99 cells/µL (HR: 0.66; 95% CI: 0.56–0.78) and 100–199 cells/µL (HR: 0.78; 95% CI: 0.62–0.98). Conclusion Cotrimoxazole prophylaxis started early during ART reduced mortality and should be offered to HIV-infected patients in low- and middle-income countries.

ملخص الغرض تقييم ما إذا كانت الوقاية باستخدام الكوتريموكسازول في مرحلة مبكرة خلال العلاج بمضادات الفيروسات القهقرية يقلل معدل الوفيات بين البالغين المصابين ب...

Resumen Objetivo Evaluar si la profilaxis con cotrimoxazol en una etapa temprana de la terapia antirretroviral (TAR) reduce la mortalidad en adultos de origen chino infectados por el virus de la inmunodeficiencia humana (VIH). Métodos Se llevó a cabo un estudio de cohorte observacional retrospectivo utilizando los datos de la base de datos nacional de China de antirretrovirales de uso gratuito. Por otro lado, se realizó un seguimiento a pacientes mayores de 14 años que iniciaron el tratamiento con TAR entre el 1 de enero de 2010 y el 31 de diciembre de 2012 y con recuento basal de linfocitos T CD4+ (célula CD4+) inferior a 200 células/µl hasta su muerte, la pérdida de seguimiento o el 31 de diciembre de 2013. Se calcularon los cocientes de riesgos (CR) para diversas variables mediante análisis multivariados. Resultados En el análisis participaron 23 816 pacientes infectados por el VIH, 2706 de los cuales fallecieron durante el seguimiento. La mortalidad entre los pacientes que iniciaron y no iniciaron el tratamiento con cotrimoxazol durante los primeros 6 meses de la TAR fue de 5,3 y 7,0 por 100 personas/años, respectivamente. Cotrimoxazol se asoció a una reducción del 37 % en la mortalidad (cociente de riesgos, CR: 0,63, intervalo de confianza del 95 %, IC: 0,56 – 0,70). Además de la TAR, cotrimoxazol redujo la mortalidad considerablemente durante el seguimiento de 6 meses (CR: 0,65; IC del 95 %: 0,59 – 0,73), 12 meses (CR: 0,58; IC del 95 %: 0,49 – 0,70), 18 meses (CR: 0,49; IC del 95 %: 0,38 – 0,63) y 24 meses (CR: 0,66; IC del 95 %: 0,48 – 0,90). La reducción de la mortalidad resultó evidente en pacientes con recuento basal de células CD4+ inferior a 50 células/µl (CR: 0,60; IC del 95 %: 0,54 – 0,67), 50 – 99 células/µl (CR: 0,66; IC del 95 %: 0,56 – 0,78) y 100 – 199 células/µl (CR: 0,78; IC del 95 %: 0,62 – 0,98). Conclusión La profilaxis con cotrimoxazol iniciada en una etapa temprana de la TAR redujo la mortalidad y debe ofrecerse a los pacientes infectados por el VIH en países de ingresos bajos y medios.

BACKGROUND: Hepcidin, encoding by HAMP gene, is the pivotal regulator of iron metabolism, controlling the systemic absorption and transportation of irons from intracellular stores. Abnormal levels of HAMP expression alter plasma iron parameters and lead to iron metabolism disorders. Therefore,itis animportant goal to understand the mechanisms controlling HAMP gene expression. RESULTS: Overexpression of Sox2 decrease basal expression of HAMP or induced by IL-6 or BMP-2, whereas, knockdown of Sox2 can increase HAMP expression, furthermore, two potential Sox2-binding sites were identified within the human HAMP promoter. Indeed, luciferase experiments demonstrated that deletion of any Sox2-binding site impaired the negative regulation of Sox2 on HAMP promoter transcriptional activity in basal conditions. ChIP experiments showed that Sox2 could directly bind to these sites. Finally, we verified the role of Sox2 to negatively regulate HAMP expression in human primary hepatocytes. CONCLUSION: We found that Sox2 as a novel factor to bind with HAMP promoter to negatively regulate HAMP expression, which may be further implicated as a therapeutic option for the amelioration of HAMP-overexpression-related diseases, including iron deficiency anemia.