ABSTRACT Objective: A common problem with antithyroid drugs (ATD) treatment in patients with Graves’ disease (GD) is the high recurrence rate after drug withdrawal. Identifying risk factors for recurrence is crucial in clinical practice. We hereby prospectively analyze risk factors for the recurrence of GD in patients treated with ATD in southern China. Subjects and methods: Patients who were newly diagnosed with GD and aged > 18 years were treated with ATD for 18 months and followed up for 1 year after ATD withdrawal. Recurrence of GD during follow-up was assessed. All data were analyzed by Cox regression with P values < 0.05 considered statistically significant. Results: A total of 127 Graves’ hyperthyroidism patients were included. During an average follow-up of 25.7 (standard deviation = 8.7) months, 55 (43%) had a recurrence within 1 year after withdraw of anti-thyroid drugs. After adjustment for potential confounding factors, the significant association remained for the presence of insomnia (hazard ratio (HR) 2.94, 95% confidence interval (CI) 1.47-5.88), greater goiter size (HR 3.34, 95% CI 1.11-10.07), higher thyrotrophin receptor antibody (TRAb) titer (HR 2.66, 95% CI 1.12-6.31) and a higher maintenance dose of methimazole (MMI) (HR 2.14, 95% CI 1.14-4.00). Conclusions: Besides conventional risk factors (i.e., goiter size, TRAb and maintenance MMI dose) for recurrent GD after ATD withdraw, insomnia was associated with a 3-fold risk of recurrence. Further clinical trials investigating the beneficial effect of improving sleep quality on prognosis of GD are warranted.

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

Abstract Cryptotanshinone (CPT), a terpenoid isolated from the roots of Salvia miltiorrhiza Bunge, was reported to have neuroprotective effects against cerebral ischemic stroke. However, the exact molecular mechanism underlying its neuroprotective ability remains unclear. The present study aimed to explore the regulatory effects of CPT on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell injury in a model of hippocampal neurons. Our results demonstrated that CPT improved cell viability and reduced the lactate dehydrogenase leakage in OGD/R-stimulated hippocampal neurons. In addition, CPT significantly inhibited oxidative stress and apoptosis in hippocampal neurons after OGD/R stimulation. Furthermore, CPT significantly enhanced the nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in hippocampal neurons exposed to OGD/R. Moreover, Nrf2 knockdown reversed the anti-apoptotic and anti-oxidant activities of CPT in primary hippocampal neurons exposed to OGD/R. In conclusion, these findings demonstrated that CPT attenuated oxidative stress and neuronal apoptosis after OGD/R injury through the activation of Nrf2/HO-1 signaling pathway in hippocampal neurons. Thus, CPT may be a novel therapeutic agent for cerebral I/R injury.

Resumo: Governança significa a política e a estratégia adotadas no processo de gestão de um país. Na longa história de mais de dois mil anos, o confucionismo tornou-se o núcleo cultural e a doutrina política da autocracia imperial, e a teoria da “governança de todo o país” contida nele tornou-se uma categoria importante na cultura tradicional chinesa. Deve-se aprofundar na rica conotação do pensamento de governança confucionista e construir um sistema de governança nacional que se adapte à sociedade, à situação geral e ao futuro, por meio de desenvolvimento inovador e transformação criativa, de modo a permitir que a excelente cultura tradicional chinesa retorne à base, para abrir um novo caminho e fazer o passado servir ao presente, fornecendo, assim, importante orientação teórica e referência histórica para o grande rejuvenescimento da nação chinesa.

Abstract: Governance means the policy and strategy adopted in the process of running a country. In the long history of more than two thousand years, Confucianism had become the cultural core and political doctrine of the imperial autocracy, and the theory of “governance of the whole country” contained in it had become an important category in traditional Chinese culture. We should dig deep into the rich connotation of Confucian governance thought, and build a national governance system that suits society, the overall situation and future through innovative development and creative transformation, so as to let excellent traditional Chinese culture return to open a new road and make the past serve the present, thus providing important theoretical guidance and historical reference for the great rejuvenation of the Chinese nation.

Abstract Serrapeptase, a proteolytic enzyme, has been used for the adjuvant treatment of many diseases. However, its fibrinolytic activity is still uncertain. Herein, the fibrinolytic activity of serrapeptase and its in vitro thrombolytic effects were investigated. The results showed that the fibrinolytic activity of serrapeptase was 1295 U/mg, and the specific activity was 3867 U/mg of protein when its proteolytic activity toward casein was 2800 U/mg. The optimum temperature and pH for serrapeptase activity were 37-40°C and 9.0, respectively. At 1 mmol/L, Zn2+, Mn2+ and Fe2+ could activate the fibrinolytic activity of serrapeptase, while K+, Cu2+, sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA) inhibited it. In vitro tests showed that serrapeptase could completely prevent blood coagulation at 150 U/mL, and the percentage of blood clot lysis reached 96.6% at 37°C after 4 h at 300 U/mL. These results indicate that serrapeptase has excellent fibrinolytic activity, and can be used as a health food or candidate drug for the prevention or treatment of thrombotic diseases.

RESUMEN En este estudio se establece el modelo de predicción de la productividad zonal en los pozos horizontales fracturados en reservorios compactos con base en un modelo físico de pozos horizontales fracturados para estudiar el regimen de filtración en reservorios compactos no convencionales. Los autores utilizaron la transformación conforme y el método de reiteración para resolver el problema. Se estudió la optimización de los parámetros de producción en pozos horizontales fracturados en comparación con los métodos de Fan Zifei y de Ning Zhengfu. Además, se analizaron los efectos de la presión inicial de la inclinación y el complejo de fracturas en la productividad de los pozos horizontales con el índice de fracturamiento. El análisis de regresión multivariante se utilizó para clasificar la importancia de los factores influenciadores. Los resultados muestran que la presión inicial de la inclinación tiene el mayor impacto en la capacidad. El ejemplo de aplicación de pozos horizontales fracturados en el reservorio compacto de Lucaogou muestra que el modelo de productividad zonal que se estableció en este estudio puede usarse para predecir la productividad inicial en estos pozos. De este modo, a través del análisis teórico y la simulación numérica, el modelo de predicción de productividad de pozos horizontales fracturados tiene una significancia para el desarrollo efectivo de reservorios compactos.

ABSTRACT The zonal productivity prediction model of volume fractured horizontal wells in tight reservoirs is established in this study based on the physical model of volume fractured horizontal wells to study the near-well seepage law of volume fractured horizontal wells in unconventional tight reservoirs. The conformal transformation and iteration method are used to solve the problem. Compared with Fan Zifei's and Ning Zhengfu's method, the optimization of fractured horizontal wells' production parameters is studied. The effects of starting pressure gradient and fracture cluster number on horizontal wells' productivity with volume fracturing are analyzed. Multivariate regression analysis is used to rank the importance of influencing factors. The results show that the starting pressure gradient has the most significant impact on capacity. The application example of volume fractured horizontal wells in Lucaogou tight reservoir shows that the zonal productivity model established in this study can be used to predict the initial productivity of volume fractured horizontal wells. Thus, through theoretical analysis and numerical simulation, the productivity prediction model of horizontal wells with volume fracturing has certain guiding significance for the effective development of tight reservoirs.

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.

Aggrecanase-2 (ADAMTS5) gene is responsible for aggrecan degradation that may contribute to cartilage destruction in a mouse osteoarthritis (OA) model. We aimed to investigate the effects of ADAMTS5 gene polymorphisms on OA risk in a Chinese population. A total of 300 OA patients and 300 controls were recruited and their genotypes for ADAMTS5 gene rs226794 and rs2830585 polymorphisms were determined using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ kit. ADAMTS5-associated genes were identified by co-expression analysis and their functions were investigated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Bioinformatics analysis showed that ADAMTS5 was significantly related to the components, structural constituent, and organization of the extracellular matrix. The rs2830585 polymorphism, but not rs226794 polymorphism, was significantly associated with an increased risk of knee OA. Stratified analysis further confirmed this significant association in patients at age ≥55 years. In conclusion, the ADAMTS5 rs2830585 polymorphism may be involved in the development of knee OA by destroying the extracellular matrix, but this finding should be further confirmed by larger studies.

Abstract This study aimed to determine the association between the polymorphisms and haplotypes in the xeroderma pigmentosum group D (XPD) gene and the risk of pancreatic cancer in the Chinese Han population. SNaPshot was used for genotyping six SNP sites of the XPD gene. Comparisons of the correlations between different genotypes in combination with smoking and the susceptibility to pancreatic cancer were performed. Individual pancreatic cancer risk in patients who carry mutant C alleles (AC, CC, and AC+CC) at rs13181 increased (p < 0.05). Taking non-smoking individuals who carry the AA genotype as a reference, and non-smoking individuals who carry mutant allele C (AC+CC), the risk of pancreatic cancer increased by 3.343 times in individuals who smoked ≥ 20 cigarettes daily, 3.309 times in individuals who smoked ≥ 14 packs per year, 5.011 times in individuals who smoked ≥ 24 packs per year, and 4.013 times in the individuals who smoked ≥ 37 packs per year (P < 0.05). In addition, haplotype analysis revealed that haplotype AGG, which comprised rs13181, rs3916874 and rs238415, was associated with a 1.401-fold increase in pancreatic cancer risk (p < 0.05). We conclude that the polymorphism of XPD Lys751Gln (rs13181) in combination with smoking contributes to increased risk of pancreatic cancer in the Chinese Han population. Haplotype AGG might be a susceptibility haplotype for pancreatic cancer.

ABSTRACT Bombyx mori nucleopolyhedrovirus (BmNPV) disease is one of the most serious silkworm diseases, and it has caused great economic losses to the sericulture industry. So far, the disease has not been controlled effectively by therapeutic agents. Breeding resistant silkworm varieties breeding may be an effective way to improve resistance to BmNPV and reduce economic losses. A precise resistance-detection method will help to accelerate the breeding process. For this purpose, here we described the individual inoculation method (IIM). Details of the IIM include pathogen BmNPV preparation, mulberry leaf size, pathogen volume, rearing conditions, course of infection, and breeding conditions. Finally, a resistance comparison experiment was performed using the IIM and the traditional group inoculation method (GIM). The incidence of BmNPV infection and the within-group variance results showed that the IIM was more precise and reliable than the GIM.

Abstract Purpose: To investigate dynamically the X-ray appearance of cervical degenerative disease induced by unbalanced dynamic and static forces in rats. Methods: A total of 60 Sprague Dawley rats were randomized into test (n=45) and control (n=15) groups, which were randomly subdivided into the one-, three- and six-month post-operative groups. The test group included 10, 15 and 20 rats at the respective corresponding post-operative stage and the control group included five rats at each time-point. By excising cervicodorsal muscles, interspinous ligaments and supraspinous ligament of rats in the test group, the balance of dynamic and static forces on cervical vertebrae was disrupted to establish a rat model of cervical degeneration. Spinal X-ray images were acquired, and intervertebral disc space and intervertebral foramen size were measured at one, three and six months post-operation. The results were analyzed and compared among groups. Results: Cervical dynamic and static imbalance accelerated the appearance of cervical degenerative disease on X-ray. Conclusion: Cervical degenerative disease may be induced by unbalanced dynamic and static forces in rats.

Abstract The dynamic response and microstructure evolution of oxygen-free high-conductivity copper in a shaped charge liner are investigated through microstructural examination of a soft-recovery EFP. Adiabatic shear bands and voids which is the failure original of copper EFP can be observed in the rear part of the projectile. Numerical simulation results illustrate that the highest plastic strain reaches about 2.9 which can fully accommodate the grains deformation of copper EFP during the formation process at strain rates of the order of 104s−1. Theoretical calculation results indicate that the highest temperature increase of EFP caused by shock wave and plastic deformation can reach 747K, which is 0.55T m (where T m is the melting temperature of copper). The main body of the EFP undergoes completely dynamic recrystallisation, and the average size of the refined grains significantly decreases to approximately 10µm. A slight increase in grain size occurs mainly away from the center and extends towards the head and rear sections of the EFP. During the DRX process, the dislocation movement is believed to be the controlling mechanism significantly refining the microstructure.

Neste trabalho, propõe-se um novo método de remoção de ruído para imagens hiperspectrais avaliado com dados reais e simulados. Um cubo de predições de imagens hiperespectrais é calculado por regressão linear múltipla no domínio espectral com base na alta correlação do sinal útil e na não correlação do ruído aleatório nas bandas hiperespectrais É aplicada uma transformada complexa de wavelet bi-dimensional no domínio espectral derivado, no qual os níveis de ruído são temporariamente elevados para impedir a deformação do sinal durante a remoção do ruído, e então a compressão bivariada foi usado para compactar os coeficientes da transformada wavelet. Os resultados experimentais demonstraram que o método proposto possibilita obter resultados melhores do que outros métodos de remoção de ruídos encontrados na literatura, com melhoria da razão de ruído do sinal de 0.5dB para 10dB. Os dados reais utilizados mostraram que o método proposto é válido e efetivo.

In this paper, a new denoising method is proposed for hyperspectral remote sensing images, and tested on both the simulated and the real-life datacubes. Predicted datacube of the hyperspectral images is calculated by multiple linear regression in the spectral domain based on the strong spectral correlation of the useful signal and the inter-band uncorrelation of the random noise terms in hyperspectral images. A two dimensional dual-tree complex wavelet transform is performed in the spectral derivative domain, where the noise level is elevated temporarily to avoid signal deformation during the wavelet denoising, and then the bivariate shrinkage is used to shrink the wavelet coefficients. Simulated experimental results demonstrate that the proposed method obtains better results than the other denoising methods proposed in the reference, improves the signal to noise ratio up to 0.5dB to 10dB. The real-life data experiment shows that the proposed method is valid and effective.

Background: Hyalodendriella sp. Ponipodef12, an endophytic fungus from a poplar hybrid, was a high producer of botrallin and TMC-264 with various bioactivities. In this study, the influences of eight metal ions (i.e.,Mn2+,Na+, Mg2+,Zn2+,Cu2+,Fe2+,Fe3+ and Al3+) on botrallin and TMC-264 production in liquid culture of the endophytic fungus Hyalodendriella sp. Ponipodef12 were investigated. Results: Three most effective metal ions (Zn2+,Cu2+ and Mg2+) along with their optimum concentrations were screened. The optimum addition time and concentrations of Zn2+,Cu2+ and Mg2+ were further obtained respectively for improving botrallin and TMC-264 production. The combination effects of Zn2+,Cu2+ and Mg2+ on the production of botrallin and TMC-264 by employing statistical method based on the central composite design (CCD) and response surface methodology (RSM) were evaluated, and two quadratic predictive models were developed for botrallin and TMC-264 production. The yields of botrallin and TMC-264, which were predicted as 144.12 mg/L and 36.04 mg/L respectively, were validated to be 146.51 mg/L and 36.63 mg/L accordingly with the optimum concentrations of Zn2+ at 0.81 mmol/L, Cu2+ at 0.20 mmol/L, and Mg2+ at 0.13 mmol/L in medium. Conclusion: The results indicated that the enhancement of botrallin and TMC-264 accumulation in liquid culture of the endophytic fungus Hyalodendriella sp. Ponipodef12 by the metal ions and their combination should be an effective strategy.

OBJECTIVE: To determine the range of motion and stability of the human cadaveric cervical spine after the implantation of a novel artificial disc and vertebra system by comparing an intact group and a fusion group. METHODS: Biomechanical tests were conducted on 18 human cadaveric cervical specimens. The range of motion and the stability index range of motion were measured to study the function and stability of the artificial disc and vertebra system of the intact group compared with the fusion group. RESULTS: In all cases, the artificial disc and vertebra system maintained intervertebral motion and reestablished vertebral height at the operative level. After its implantation, there was no significant difference in the range of motion (ROM) of C3-7 in all directions in the non-fusion group compared with the intact group (p>0.05), but significant differences were detected in flexion, extension and axial rotation compared with the fusion group (p<0.05). The ROM of adjacent segments (C3-4, C6-7) of the non-fusion group decreased significantly in some directions compared with the fusion group (p<0.05). Significant differences in the C4-6 ROM in some directions were detected between the non-fusion group and the intact group. In the fusion group, the C4-6 ROM in all directions decreased significantly compared with the intact and non-fusion groups (p<0.01). The stability index ROM (SI-ROM) of some directions was negative in the non-fusion group, and a significant difference in SI-ROM was only found in the C4-6 segment of the non-fusion group compared with the fusion group. CONCLUSION: An artificial disc and vertebra system could restore vertebral height and preserve the dynamic function of the surgical area and could theoretically reduce the risk of adjacent segment degeneration compared with the anterior fusion procedure. However, our results should be considered with caution because of the low power of the study. The use of a larger sample should be considered in future studies.