Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Development of the Soft X-ray AGM-AGS RIXS beamline at the Taiwan Photon Source.

We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4 meV at 530 eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5 eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.

[Correlation between spatial navigation disorder and white matter hyperintensity in patients with mild cognitive impairment].

Objective: To investigate the relationship between white matter lesions and spatial navigation ability in patients with mild cognitive impairment (MCI). Methods: A total of 32 MCI patients [age (66±11) years, 16 males and 16 females] who were treated in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2015 to February 2018 were selected, and matched with age, gender and education level of 28 healthy controls (NC) [age (70±11) years, 19 males and 9 females] underwent spatial navigation ability test and neuropsychology scale evaluation. In the cross-sectional study, all subjects simultaneously underwent 3.0T magnetic resonance three-dimensional liquid inversion recovery sequence and high-resolution T(1) weighted imaging scan. The Wisconsin White Matter Hyperintensities Segmentation Toolbox (W2MHS) was used to automatically mark and extract the volume of the white matter hyperintensity. Results: The average error distances of egocentric virtual (P=0.002) and allocentric virtual (P=0.039) of MCI patients are greater than that of the control group, but the average error distance of mixed (allocentric-egocentric virtual) navigation had no statistic difference between two groups (P=0.070). The volume of the whole white matter hyperintensity, periventricular white matter hyperintensity, and deep white matter hyperintensity showed no significant differences between two groups (all P>0.05). Partial correlation analysis showed that after controlling for age, gender, education level and whole brain volume, the average error distance of mixed (allocentric-egocentric virtual) navigation in MCI patients was positively correlated to the volume of the whole white matter hyperintensity, deep white matter intensity, and periventricular white matter hyperintensity (r=0.469, 0.434, 0.512, all P<0.05). The average error distance of allocentric virtual navigation is positively correlated with the volume of periventricular white matter hyperintensity (r=0.403, P=0.033). There is no correlation between the average error distance of egocentric virtual navigation and the hyperintensity of white matter. Conclusions: The spatial navigation ability of patients with MCI is related to white matter lesions, which is of great significance for further research on the potential biological mechanisms affecting human spatial navigation ability.

Numerical investigation of cavitation generated by an ultrasonic dental scaler tip vibrating in a compressible liquid.

Bacterial biofilm accumulation around dental implants is a significant problem leading to peri-implant diseases and implant failure. Cavitation occurring in the cooling water around ultrasonic scaler tips can be used as a novel solution to remove debris without any surface damage. However, current clinically available instruments provide insufficient cavitation around the activated tip surface. To solve this problem a critical understanding of the vibro-acoustic behaviour of the scaler tip and the associated cavitation dynamics is necessary. In this research, we carried out a numerical study for an ultrasound dental scaler with a curved shape tip vibrating in water, using ABAQUS based on the finite element method. We simulated the three-dimensional, nonlinear and transient interaction between the vibration and deformation of the scaler tip, the water flow around the scaler and the cavitation formation and dynamics. The numerical model was well validated with the experiments and there was excellent agreement for displacement at the free end of the scaler. A systematic parametric study has been carried out for the cavitation volume around the scaler tip in terms of the frequency, amplitude and power of the tip vibration. The numerical results indicate that the amount of cavitation around the scaler tip increases with the frequency and amplitude of the vibration. However, if the frequency is far from the natural frequency, the cavitation volume around the free end decreases due to reduced free end vibration amplitude.

Multi-messenger nanoprobes of hidden magnetism in a strained manganite.

The ground-state properties of correlated electron systems can be extraordinarily sensitive to external stimuli, offering abundant platforms for functional materials. Using the multi-messenger combination of atomic force microscopy, cryogenic scanning near-field optical microscopy, magnetic force microscopy and ultrafast laser excitation, we demonstrate both 'writing' and 'erasing' of a metastable ferromagnetic metal phase in strained films of La2/3Ca1/3MnO3 (LCMO) with nanometre-resolved finesse. By tracking both optical conductivity and magnetism at the nanoscale, we reveal how strain-coupling underlies the dynamic growth, spontaneous nanotexture and first-order melting transition of this hidden photoinduced metal. Our first-principles calculations reveal that epitaxially engineered Jahn-Teller distortion can stabilize nearly degenerate antiferromagnetic insulator and ferromagnetic metal phases. We propose a Ginzburg-Landau description to rationalize the co-active interplay of strain, lattice distortions and magnetism nano-resolved here in strained LCMO, thus guiding future functional engineering of epitaxial oxides into the regime of phase-programmable materials.

[Association of miRNA-196b-5p and miRNA-99a-5p with autophagy and apoptosis in multiple myeloma cells].

Objective: To investigate the relationship between miRNA-196b-5p and miRNA-99a-5p expression and autophagy and apoptosis in multiple myeloma cells. Methods: Human myeloma cell line U266 and normal CD138+ plasma cells were selected as the research objects. The subjects were divided into 45 cases of multiple myeloma patients and 40 healthy controls. The expression of miRNA-196b-5p and miRNA-99a-5p was measured by real-time quantitative PCR, and Western blot was used to determine the expression of autophagy related protein LC3-Ⅱ, LC3-Ⅰ, P62, Beclin-1 expression, apoptosis related protein CL caspase3, CL caspase7, Bcl-2, Bax, and TGF-ß/Smad pathway associated proteins TGF-ß1, Smad2/3, p-Smad3 and Smad7. The cell apoptosis rate was determined by flow cytometry. The correlation between miRNA expression level and clinical characteristics of multiple myeloma patients was analyzed. Results: Compared with normal plasma cells, the expression of miRNA-196b-5p in myeloma cells increased significantly (0.43±0.15 vs 2.44±0.63 or 2.02±0.85, all P<0.001), the expression of miRNA-99a-5p was significantly decreased (1.87±0.61 vs 0.62±0.15 or 0.80±0.33, P<0.001), LC3-Ⅱ/LC3-Ⅰ increased significantly (P<0.05), Beclin-1 expression increased significantly (P<0.05), P62 expression decreased significantly (P<0.05). The expression of Bax, CL caspase3 and CL caspase7 decreased significantly (P<0.05), and the expression of Bcl-2 increased significantly (P<0.05) and apoptosis rate significantly decreased (P<0.05). After transfected with miRNA-196b-5p mimic or miRNA-99a-5p inhibitor, the LC3-Ⅱ/LC3-Ⅰ of CD138+ plasma cells increased significantly (P<0.05), the expression of Beclin-1 increased significantly (P<0.05), P62 expression decreased significantly (P<0.05), and the apoptosis rate significantly decreased (P<0.05). However, after autophagy inhibitor of 3-MA was administered, the apoptotic rate of the above reaction system did not change significantly (P>0.05). The expression of miRNA-196b-5p and miRNA-99a-5p was significantly correlated with DS and ISS stage in multiple myeloma patients (P<0.05). Conclusion: miRNA-196b-5p and miRNA-99a-5p are closely related to the clinical characteristics of patients with multiple myeloma. The overexpression of miRNA-196b-5p and down regulation of miRNA-99a-5p could inhibit the apoptosis of myeloma cells by up regulation of autophagy, and the mechanism is related to the activation of the TGF-ß/Smad signaling pathway.

In vitro 3D regeneration-like growth of human patient brain tissue.

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 µm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models.

Coulomb Correlations Intertwined with Spin and Orbital Excitations in LaCoO_{3}.

We carried out temperature-dependent (20-550 K) measurements of resonant inelastic x-ray scattering on LaCoO_{3} to investigate the evolution of its electronic structure across the spin-state crossover. In combination with charge-transfer multiplet calculations, we accurately quantified the renomalized crystal-field excitation energies and spin-state populations. We show that the screening of the effective on-site Coulomb interaction of 3d electrons is orbital selective and coupled to the spin-state crossover in LaCoO_{3}. The results establish that the gradual spin-state crossover is associated with a relative change of Coulomb energy versus bandwidth, leading to a Mott-type insulator-to-metal transition.

Jahn-Teller distortion driven magnetic polarons in magnetite.

The first known magnetic mineral, magnetite, has unusual properties, which have fascinated mankind for centuries; it undergoes the Verwey transition around 120 K with an abrupt change in structure and electrical conductivity. The mechanism of the Verwey transition, however, remains contentious. Here we use resonant inelastic X-ray scattering over a wide temperature range across the Verwey transition to identify and separate out the magnetic excitations derived from nominal Fe2+ and Fe3+ states. Comparison of the experimental results with crystal-field multiplet calculations shows that the spin-orbital dd excitons of the Fe2+ sites arise from a tetragonal Jahn-Teller active polaronic distortion of the Fe2+O6 octahedra. These low-energy excitations, which get weakened for temperatures above 350 K but persist at least up to 550 K, are distinct from optical excitations and are best explained as magnetic polarons.

lncRNA NEAT1 is closely related with progression of breast cancer via promoting proliferation and EMT.

OBJECTIVE: Breast cancer (BC) is one of the most common cancers in females. Abnormal proliferation and metastasis are key reasons that cause mortality in BC patients. More and more evidence showed that lncRNA played an important role in the BC development, but the mechanism was not well established. PATIENTS AND METHODS: The expression of lncRNA NEAT1 was detected in 40 BC patients by qRT-PCR technology. MTT and Wound Healing assays were applied to detect the effect of lncRNA NEAT1 in proliferation and metastasis in BC. Western blot was used to detect possible protein, which was regulated by lncRNA NEAT1. RESULTS: lncRNA NEAT1 was highly expressed in BC tissue, and the expression was also closely related to the tumor size and lymph node metastasis. Survival study also showed that the expression of lncRNA NEAT1 was closely related with prognosis of BC patients. MTT and Wound Healing assays showed that suppression of lncRNA NEAT1 could lead to decreased proliferation and metastasis in BC cell lines. Western blot also showed that ß-catenin and N-cad were decreased while E-cad was increased after lncRNA NEAT1 being suppressed. CONCLUSIONS: lncRNA NEAT1 may act as an oncogene in BC, which can promote proliferation and metastasis of BC.

[Change of white matter neuronal integrity associated with spatial navigation impairment in mild cognitive impairment].

Objective: To analyze the correlation between white matter integrity and spatial navigation impairment in patients with mild cognitive impairment (MCI). Methods: A total of 27 MCI subjects and 24 healthy controls were enrolled from the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2015 to February 2016, who underwent 3.0 T MRI scan and 2D-computer version spatial navigation test.DTI preprocessing and tract-based spatial statistics (TBSS) were performed by PANDA.Two sample t-test and partial correlation coefficients were performed to investigate the correlation of white matter impairments and spatial navigation decline. Results: Relative to controls, MCI showed worse egocentric navigation (t=-2.202, P<0.05). Decreased FA in superior longitudinal fasciculus (left t=2.95, right t=2.95, P<0.05), inferior longitudinal fasciculus and inferior fronto-occipital fasciculus (left t=2.66, right t=2.96, P<0.05), corpus callosum (t=2.09, P<0.05), cingulum (left t=2.76, right t=2.41, P<0.05), fornix (t=4.83, P<0.05), and corticospinal tract (left t=2.33, right t=2.26, P<0.05), were found in the MCI subjects.The decreased FA value of superior longitudinal fasciculus (left r=-0.354, right r=-0.347, P<0.05), inferior longitudinal fasciculus (left r=-0.338, right r=-0.336, P<0.05), cingulum (left r=-0.395, right r=-0.370, P<0.05), right corticospinal tract (r=-0.362, P<0.05) and fornix (r=-0.369, P<0.05) were correlated with increased ego average total error.Allo average total error were negative correlated with FA value of superior longitudinal fasciculus (left r=-0.329, right r=-0.350, P<0.05), inferior longitudinal fasciculus (left r=-0.349, right r=-0.378, P<0.05), splenium of corpus callosum (r=-0.364, P<0.05) and cingulum (left r=-0.340, right r=-0.406, P<0.05). Conclusion: This study implicated the potential white matter structural basis of spatial navigation impairment and will have an impact on the further study of the neurobiological mechanisms of human spatial navigation ability.

[A control study of artificial oocyte activation in the same period].

Objective: To compare the fertility rate and embryo outcome between normal fertilization and the use of Calcium ionophore A23187 on the same period of the same cycle of human ovum for artificial activation. Methods: Patients who conducted the intracytoplasmic sperm injection (ICSI) cycle in vitro fertilization assisted reproductive from January 2015 to December in reproductive center of the Third Affiliated Hospital of Zhengzhou University were enrolled.The protocol of this study was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University.The subjects must met at least one of the inclusion criteria: (1)the normal fertilization rate was less than 30% ICSI in the previous ICSI cycle; (2)no good quality embryos in a previous period of third days in ICSI; (3)patients with globozoospermia.The ovum were randomly divided into two groups, control group and artificial oocyte activation (AOA) group. In the control group, the eggs were treated with routine ICSI operation, and the AOA group was activated by A23187 after ICSI. Normal fertilization rate, cleavage rate, pregnancy and birth outcome of two groups were compared. Results: The 2PN fertilization rate in the AOA group 65.93% (60/91) was significantly higher than that in the control group 46.67% (41/89) (P<0.05). In addition, in patients who met the inclusion criteria of 1 categories (2PN≤30%), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [79.59% (39/49)] compared with the control group [57.14% (28/49)]. In patients who met the inclusion criteria of 3 categories (globozoospermia), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [75% (6/8)] compared with the control group [0% (0/5)]. Conclusions: The use of calcium ionophore A23187 assisted activation could be helpful to improve the normal fertilization rate of ICSI. But the effects of early embryonic development and the safety of generation need to be further studied.

[Study on the difference of blood coagulation function in patients with traumatic brain injury in plain and plateau area].

Objective: In this study, we tested platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APTT), and other indicators of coagulation function, and revealed their difference in patients with traumatic brain injury (TBI) between plain and plateau area. Base on the results, we may provide research basis for the therapy of TBI associated coagulopathy in different areas. Methods: 151 TBI patients from Tianjin Medical University General Hospital, and 74 from People's Hospital of Tibet Autonomous Region in the period from Dec 2013 to Dec 2015 were enrolled.Coagulation function, including PC, platelet distribution width (PDW), mean platelet volume (MPV), platelet - large cell ratio (P- LCR), PT, APTT, fibrinogen (FIB), and D- Dimer were tested within 8 h. The difference in patients with TBI between plain and plateau areas were compared and analyzed. Results: Compared with plain area, the PC of patients with TBI in plateau area is lower [(168±49)×109/L vs (196±72)×109/L, P<0.05], while PT and APTT were extended [(13.5±1.3) s vs (12.0±4.0) s, (38±4) s vs(27±6) s, P<0.01]. On the other hand, FIB increases [(3.1±1.2) g/L vs (2.6±1.0) g/L, P<0.01] and D-Dimer decreases [(3.1±3.3) µg/L vs (4.7±3.6) µg/L, P<0.01] in plateau area compared with plain area. Conclusion: Due to the people of plateau area living in hypoxia state, the coagulation function is activated for a long time.Once TBI happens, the platelets and coagulation factors may be excessive consumption, resulting in hypocoagulable state and high risk of rebleeding, while the fibrinolysis system in patients with TBI of plateau area is not activated obviously.Therefore, it should give full consideration to these differences in the treatment of patients with TBI in plateau area, instead of directly copying the standard therapy of the people in plain area.The treatment recommendations should primarily supplement coagulation materials, and antifibrinolytics may unlikely have the therapy effect.

Orbital Engineering in Nickelate Heterostructures Driven by Anisotropic Oxygen Hybridization rather than Orbital Energy Levels.

Resonant inelastic x-ray scattering is used to investigate the electronic origin of orbital polarization in nickelate heterostructures taking LaTiO_{3}-LaNiO_{3}-3×(LaAlO_{3}), a system with exceptionally large polarization, as a model system. We find that heterostructuring generates only minor changes in the Ni 3d orbital energy levels, contradicting the often-invoked picture in which changes in orbital energy levels generate orbital polarization. Instead, O K-edge x-ray absorption spectroscopy demonstrates that orbital polarization is caused by an anisotropic reconstruction of the oxygen ligand hole states. This provides an explanation for the limited success of theoretical predictions based on tuning orbital energy levels and implies that future theories should focus on anisotropic hybridization as the most effective means to drive large changes in electronic structure and realize novel emergent phenomena.

[Application of frailty index for comprehensive geriatric assessment in the elderly in China].

OBJECTIVE: To discuss the suitability of frailty index for comprehensive geriatric assessment(FI-CGA)in the elderly in China, and evaluate the application of FI-CGA in China. METHODS: A comprehensive geriatric assessment was conducted among 118 old adults receiving health examination, and frailty index was calculated. Clinical frailty scale(CFS)was also used to evaluate the frail status of the old adults. The correlation between FI-CGA value and CFS level of the old adults was analyzed. RESULTS: The mean value of FI-CGA was 0.19 ± 0.07, and the average level of CFS was 3.11 ± 1.46. Women had higher mean value of FI-CGA and higher CFS level than men(FI-CGA= 0.20 ± 0.02 for women, 0.19 ± 0.07 for men; CFS =3.40 ± 0.55 for women, 3.10 ± 1.48 for men), but the differences had no significance(t=0.270, 0.452, P=0.788, 0.652). The FI-CGA value and CFS level increased with age(F=10.437, 5.651, P=0.000, 0.001); and there was a positive correlation between FI-CGA value and CFS level(r=0.615, P=0.000). CONCLUSION: FI-CGA is an effective model for the quantitative evaluation of the frail status of the elderly, and can be used in the clinical practice of geriatric medicine.

Raman and fluorescence characteristics of resonant inelastic X-ray scattering from doped superconducting cuprates.

Measurements of spin excitations are essential for an understanding of spin-mediated pairing for superconductivity; and resonant inelastic X-ray scattering (RIXS) provides a considerable opportunity to probe high-energy spin excitations. However, whether RIXS correctly measures the collective spin excitations of doped superconducting cuprates remains under debate. Here we demonstrate distinct Raman- and fluorescence-like RIXS excitations of Bi1.5Pb0.6Sr1.54CaCu2O(8+δ). Combining photon-energy and momentum dependent RIXS measurements with theoretical calculations using exact diagonalization provides conclusive evidence that the Raman-like RIXS excitations correspond to collective spin excitations, which are magnons in the undoped Mott insulators and evolve into paramagnons in doped superconducting compounds. In contrast, the fluorescence-like shifts are due primarily to the continuum of particle-hole excitations in the charge channel. Our results show that under the proper experimental conditions RIXS indeed can be used to probe paramagnons in doped high-Tc cuprate superconductors.

Meta-analysis of the association between the rs7903146 polymorphism at the TCF7L2 locus and type 2 diabetes mellitus susceptibility.

Type 2 diabetes mellitus (T2DM) is a chronic disease caused by genetic and environmental factors. T2DM has been associated with specific polymorphisms in the TCF7L2 gene. This study evaluates the relationship between the rs7903146 locus polymorphism of the TCF7L2 gene and T2DM susceptibility through meta-analysis; the overall aim is to provide a basis for evidence-based medicinal treatment of T2DM. Cohort and case-control studies from Medline, PubMed, EMBASE, CBM, CNKI, and academic conferences/dissertations that examined the correlation between T2DM and rs7903146 polymorphisms were evaluated. We determined whether the TCF7L2 rs7903146 locus was associated with T2DM susceptibility by comparing alleles and genotypes. The Stata 11.0 software was applied for meta-analysis, and a random-effects model was adopted for heterogeneity testing and odds ratio (OR) calculation. A fixed-effect model was used for quantitative analysis of the heterogeneity between different studies, and for calculating the percentage of variability I(2). A total of 10 studies related to the rs7903146 loci and T2DM susceptibility were enrolled; this included 3404 cases of T2DM patients and 6473 control cases. Meta-analysis showed that the T allele of rs7903146 was significantly correlated with the risk of T2DM, with both a dominant fixed-effect model (OR = 1.653, 95%CI = 1.416-1.653) and a co-dominant-fixed effect model (OR = 1.525, 95%CI = 1.350-1.723). Meta-analysis revealed that the T allele of rs7903146 was also correlated with T2DM susceptibility.

Agonist of farnesoid X receptor protects against bile acid induced damage and oxidative stress in mouse placenta--a study on maternal cholestasis model.

INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disorder, which is characterized by raised serum bile acid level and potential adverse fetal outcome. Farnesoid X receptor (FXR), also known as a bile acid receptor, was found to be expressed in placenta with low level. Whether activation of FXR by specific agonists could regulate the pathogenesis of ICP is still unclear. METHODS: A model of maternal cholestasis was induced by administration of 17α-ethynylestradiol (E2) in pregnant mice for 6 days. We explored the regulatory effect of WAY-362450 (W450), a highly selective and potent FXR agonist on placenta. RESULTS: In this study, we demonstrated that administration of E2 increased bile acid levels in mouse serum, liver and amniotic fluid. Bile acid levels were significantly decreased after W450 treatment. W450 protected against the impairment of placentas induced by E2, including severe intracellular edema and apoptosis of trophoblasts. Moreover, W450 significantly induced the expressions of FXR target bile acid transport gene ATP-binding cassette, sub-family B (MDR/TAP), member 11 (Abcb11;Bsep) in placenta. W450 could also attenuate placental oxidative stress and increase the expressions of antioxidant enzymes Prdx1 and Prdx3. DISCUSSION AND CONCLUSION: In conclusion, our data demonstrated that FXR agonist W450 modulated bile acid balance and protected against placental oxidative stress. Thus, our results support that potent FXR agonists might represent promising drugs for the treatment of ICP.

Highly efficient beamline and spectrometer for inelastic soft X-ray scattering at high resolution.

The design, construction and commissioning of a beamline and spectrometer for inelastic soft X-ray scattering at high resolution in a highly efficient system are presented. Based on the energy-compensation principle of grating dispersion, the design of the monochromator-spectrometer system greatly enhances the efficiency of measurement of inelastic soft X-rays scattering. Comprising two bendable gratings, the set-up effectively diminishes the defocus and coma aberrations. At commissioning, this system showed results of spin-flip, d-d and charge-transfer excitations of NiO. These results are consistent with published results but exhibit improved spectral resolution and increased efficiency of measurement. The best energy resolution of the set-up in terms of full width at half-maximum is 108 meV at an incident photon energy tuned about the Ni L3-edge.