[Explore the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab in patients with ulcerative colitis].

Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) µg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.

[The associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 gene polymorphisms with the risk of Crohn's disease in Chinese patients].

Objectives: The present study aimed to investigate the associations of cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) gene polymorphisms with the risk of Crohn's disease (CD) in Chinese patients. Methods: From January 2012 to January 2021, a total of 207 CD patients and 545 age-and gender-matched healthy controls were collected from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. The genotypes of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry technique. Unconditional logistic regression analysis was used to analyze the differences of CDKN2B-AS1 polymorphisms between CD patients and healthy controls, as well as their influences on the clinicopathologic characteristics of CD patients. The analyses for linkage disequilibrium and haplotype were further performed by Haploview 4.2 software. Results: The variant genotype (AG+GG) and variant allele (G) of rs1063192 were more prevalent in CD patients than in healthy controls (32.4% vs 24.8%, P=0.036; 18.8% vs 13.6%, P=0.011). The same conclusions were also drawn for homozygous variant genotype (GG) and variant allele (G) of rs10757274 when CD patients were compared with healthy controls (19.8% vs 12.8%, P=0.017; 45.2% vs 38.1%, P=0.012). According to the Montreal Classification Standards, CD patients were stratified into different subgroups. The homozygous variant genotype (GG) and variant allele (G) of rs10757278 were less frequent in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (13.7% vs 29.9%, P=0.015; 37.7% vs 50.4%, P=0.022). However, all the correlations above were no longer significant after Bonferroni's correction (all P>0.05). The polymorphic loci of rs10757274, rs2383207, rs10757278, and rs1333048 were in close linkage disequilibrium with each other in CDKN2B-AS1 gene. Compared with healthy controls, the frequency of haplotype AGAC was decreased in CD patients (1.5% vs 4.5%, χ2=7.61, P=0.006), whereas the frequency of haplotype GGAC was obviously increased in CD patients (3.0% vs 0.6%, χ2=14.25, P<0.001). The stratified analysis further showed that the frequency of haplotype AGAC was higher in the patients with stricturing CD or penetrating CD than in those with non-stricturing and non-penetrating CD (3.1% vs 0.4%, χ2=5.31, P=0.021). Conclusions: The variations of CDKN2B-AS1 (rs1063192, rs10757274, rs10757278, rs1333048, rs2383207) may not independently affect the risk of CD. Among the haplotypes constructed by rs10757274, rs2383207, rs10757278, and rs1333048, the haplotype AGAC may reduce the risk of CD, whereas it may increase the risk of stricturing or penetrating in CD patients. In addition, the haplotype GGAC may increase the risk of CD.

Effects of Ag doping on the electronic and optical properties of CdSe quantum dots.

Cadmium selenide (CdSe) nanocrystals are important photoelectric materials. Doping heterovalent impurities such as silver (Ag) in CdSe nanocrystal quantum dots (QDs) can provide additional charge carriers, which can significantly enhance the performance of CdSe QDs for their potential applications in high-efficiency photovoltaic devices. Using density functional theory (DFT) based calculations with the Heyd-Scuseria-Ernzerhof (HSE06) screened hybrid functional, we demonstrate that Ag doping can affect the structural, electronic and optical properties of CdSe QDs significantly. The location and number of Ag dopant atoms are critical factors for modifying the electronic structure, in particular the change of energy position and shape of the valence and conduction band edges. It is found that doping of Ag atoms into the core region of a CdSe nanoparticle induces metallic-like electronic characteristics with a dense number of electrons emerging at the Fermi level. However, incorporation of Ag dopant into the surface of a CdSe quantum dot introduces some mid-gap states that mainly consist of Se 4p states, and results in a new sub-bandgap electronic transition from mid-gap states to the conduction band. The calculated absorption spectra indicate that doping of just one or two Ag atoms greatly strengthens the absorption in the ultraviolet-visible regime and extends the absorption edges of CdSe QDs into the infrared regime. In particular, the spectra show a high-intensity absorption band between 424 and 600 nm with just 1 Ag atom incorporated into the CdSe QDs. Based on the improved absorption spectra, the present results provide a science-based strategy for designing Ag-doped CdSe QDs with enhanced visible light absorption for their application in high-efficiency photovoltaic devices.

Engineering the electronic and magnetic properties of d(0) 2D dichalcogenide materials through vacancy doping and lattice strains.

We have systematically investigated the effects of different vacancy defects in 2D d(0) materials SnS2 and ZrS2 using first principles calculations. The theoretical results show that the single cation vacancy and the vacancy complex like V-SnS6 can induce large magnetic moments (3-4 µB) in these single layer materials. Other defects, such as V-SnS3, V-S, V-ZrS3 and V-ZrS6, can result in n-type conductivity. In addition, the ab initio studies also reveal that the magnetic and conductive properties from the cation vacancy and the defect complex V-SnS6 can be modified using the compressive/tensile strain of the in-plane lattices. Specifically, the V-Zr doped ZrS2 monolayer can be tuned from a ferromagnetic semiconductor to a metallic/half-metallic material with decreasing/increasing magnetic moments depending on the external compressive/tensile strains. On the other hand, the semiconducting and magnetic properties of V-Sn doped SnS2 is preserved under different lattice compression and tension. For the defect complex like V-SnS6, only the lattice compression can tune the magnetic moments in SnS2. As a result, by manipulating the fabrication parameters, the magnetic and conductive properties of SnS2 and ZrS2 can be tuned without the need for chemical doping.

Theoretical prediction of long-range ferromagnetism in transition-metal atom-doped d0 dichalcogenide single layers SnS2 and ZrS2.

We have systematically investigated the effects of transition-metal (TM) atom (Sc-Zn) doping in 2D d0 materials SnS2 and ZrS2via the density functional theory method. Our results demonstrate that the conductivity and magnetism of SnS2 and ZrS2 can be engineered to spin-polarize half-metal/metal with appropriate TM dopants. For both materials, nontrivial magnetic interactions can be induced by V/Cr/Mn/Fe/Co doping. Specifically, the various behaviors of the magnetic exchanges in TM-doped SnS2 and ZrS2 are due to the competition between the super-exchange, the double exchange, and the p-d exchange interactions, which are dependent on the dopants' chemistry and spatial positions. Thus, our results give potential guidance for future experiments to create functionalized d0 nano-electronic devices.

[Correlation of serum sex hormone levels with metabolic syndrome in elderly men].

OBJECTIVE: To investigate the relationship between sex hormones and metabolic syndrome (MS), as well as its components in elderly men. METHODS: 1 505 elderly men (≥60 years old, mean age 75.4±9.7 years old) who participated in a routine health screening examination in PLA general hospital from May to June in 2012 were enrolled in this cross-sectional study. Serum lipids, glucose and sex hormones were measured along with body height, weight and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. The correlation of serum sex hormones with the presence of MS and its components were analyzed. RESULTS: The prevalence of MS was 21.7% (326/1 505) in this study. Elderly men with MS had lower levels of sex hormone-binding globulin (SHBG), total testosterone (TT), FT and BT than those without MS. The levels of SHBG, TT, FT and BT were significantly lower in the overweight/obesity group, hyperglycemia group and dyslipidemia group than those in the respective control groups (P<0.05). Logistic regression analysis showed that the SHBG level was an independent risk factor for MS in elderly men(OR=0.977, 95%CI: 0.964-0.989, P<0.001), while the levels of TT, FT and BT were not associated with MS. The prevalence of MS gradually increased with decreasing of SHBG values (P<0.001). When comparing subjects in the lowest and highest quartile of SHBG, the former group demonstrated a 2.13-fold increase in the odds ratio for MS after adjusting for age, smoking, drinking and other sex hormone indices. CONCLUSION: In elderly men, lower SHBG level, not TT, FT or BT may be an independent predictor for the prevalence of MS, in which the mechanism requires further studies.

Functionalization of a GaSe monolayer by vacancy and chemical element doping.

Based on first-principles plane-wave calculations, functionalization of the two-dimensional single-layered GaSe structure through vacancy and chemical element doping has been investigated. Our calculations show that the pristine GaSe monolayer, which is normally a non-magnetic, indirect-band-gap semiconductor, can induce net magnetic moments by introduction of Ga mono-vacancy, Ga di-vacancy, and GaSe3 and Ga2Se6 vacancy complexes. Magnetic moments can also be induced by selectively doping specific transition-metal atoms as well as A group atoms. The introduced donor or acceptor states are localized in the band gap, which expands the utilization of the single-layered GaSe in nanoelectronics and spintronics. In spite of the intrinsic p-type character of the two-dimensional GaSe material, substitution of Si for Ga and substitution of Cl for Se exhibit n-type character at relatively low dopant concentrations. These findings will provide useful supplements to the experimental studies on the newly synthesized two-dimensional layered metal monochalcogenides, which allows us to go beyond the current scope that is limited to applications within graphene, BN, and transition-metal dichalcogenide-based nanostructures.

Association between the rs189037 single nucleotide polymorphism in the ATM gene promoter and cognitive impairment.

The aim of this study was to explore the existence of a relationship between the rs189037 single nucleotide polymorphism (SNP) of the ataxia telangiectasia mutated (ATM) gene and cognitive impairment in the elderly (aged 60 years and above). In a cohort, 505 residents of Suinung City were consecutively recruited and their cognitive function was measured using a 30-point Mini-Mental State Examination (MMSE). The subjects were divided into cognitive impairment group and control group on the basis of MMSE scores. Presence of the rs189037 SNP variant was examined using polymerase chain reaction-restriction fragment length polymorphism. The prevalence rates of cognitive impairment were 32.7% in the whole sample. The genotype frequencies of the rs189037 polymorphism were 33.5% (CC), 50.7% (CT), and 15.8% (TT); the C and T allele frequencies were 58.8 and 41.2%, respectively. No significant differences in the frequency distributions of the CC, CT and TT genotypes were observed between cognitively impaired and control groups. We found that the rs189037 SNP was not directly correlated with cognitive impairment among the elderly Chinese Han population.

Regulation of zinc transporter 3 and carbonic anhydrases 2 and 14 mRNA expression in the retina of rats affected by low dietary zinc.

We looked at how zinc transporter 3 ZnT-3) mRNA expression in the rat retina is affected by low dietary zinc. Groups of 12 four-week-old male Sprague Dawley rats were fed on a low-zinc diet for 2, 4 or 6 weeks. Half of each group was then fed with a normal-zinc content diet and the other half was given a low-zinc content diet. The expression of ZnT-3, carbonic anhydrase 2 (CA2) and 14 (CA14) were detected by RT-PCR. After the rats were fed a low-zinc content diet for 2 weeks, their retina CA2 and CA14 mRNA levels were decreased, and the ZnT-3 mRNA was increased compared with the control rats. After they were fed a low-zinc diet for 4 weeks, ZnT-3, CA2 and CA14 mRNA levels decreased significantly. Then, after being changed back to a normal diet for 2 weeks, the rats had ZnT-3, CA2 and CA14 mRNA levels recovery in the retina.

Electronic and magnetic properties of C-adsorbed graphene: a first-principles study.

Using density functional theory, we consider the adsorption of C on graphene, which gives rise to many interesting phenomena. A single-C at the bridge site shows a clearly covalent-bond feature with graphene, in which the metallic state occurs and a magnetic moment of 0.36 µ(B) was determined. For both-sided adsorption, the magnetic moment is remarkably larger than that in one-sided adsorption, and increases with concentration up to a coverage of 12.5%. High spin polarization obtained at the Fermi level indicates a high degree of passage of preferred spin, which is important for developing spin filters.

Electronic and magnetic properties of substituted BN sheets: a density functional theory study.

Using density functional calculations, we investigate the geometries, electronic structures and magnetic properties of hexagonal BN sheets with 3d transition metal (TM) and nonmetal atoms embedded in three types of vacancies: V(B), V(N), and V(B+N). We show that some embedded configurations, except TM atoms in V(N) vacancy, are stable in BN sheets and yield interesting phenomena. For instance, the band gaps and magnetic moments of BN sheets can be tuned depending on the embedded dopant species and vacancy type. In particular, embedment such as Cr in V(B+N), Co in V(B), and Ni in V(B) leads to half-metallic BN sheets interesting for spin filter applications. From the investigation of Mn-chain (C(Mn)) embedments, a regular 1D structure can be formed in BN sheets as an electron waveguide, a metal nanometre wire with a single atom thickness.

Pressure induced structural transformation in Gd2Ti2O7 and Gd2Zr2O7.

Ab initio total energy calculations have been performed to study the phase stability of Gd(2)Ti(2)O(7) and Gd(2)Zr(2)O(7) pyrochlores over the pressure range from 0 to 60 GPa. Both compounds are unstable under pressure, and phase transformations to the defect-cotunnite structure are predicted. The phase transformation pressure of 43.6 GPa for Gd(2)Ti(2)O(7) is considerably larger than the value of 13 GPa for Gd(2)Zr(2)O(7), in good agreement with experiments. The decreased structural stability of Gd(2)Zr(2)O(7) under pressure, relative to Gd(2)Ti(2)O(7), is a consequence of the lower compressibility of the ⟨Zr-O⟩ bond and the higher compressibility of the ⟨Gd-O⟩ bond. In addition, the Gd 4f electrons are found to have only a small effect in determining the pressure induced phase transformation.

Zirconate pyrochlores under high pressure.

Ab initio total-energy calculations and X-ray diffraction measurements have been combined to study the phase stability of zirconate pyrochlores (A(2)Zr(2)O(7); A = La, Nd and Sm) under pressures up to 50 GPa. Phase transformations to the defect-cotunnite structure are theoretically predicted at pressures of 22, 20 and 18 GPa, in excellent agreement with the experimentally determined values of 21, 22 and 18 GPa for La(2)Zr(2)O(7), Nd(2)Zr(2)O(7) and Sm(2)Zr(2)O(7), respectively. Analysis of the elastic properties indicates that elastic anisotropy may be one of the driving forces for the pressure-induced cubic-to-noncubic phase transformation.

Electronic and magnetic properties of metal-doped BN sheet: A first-principles study.

The electronic and magnetic properties of a BN sheet doped with 3d transition metals (Fe, Co and Ni) have been investigated using ab initio calculations. Our calculations show many interesting physical properties in a metal-doped BN sheet. A Fe-doped BN sheet is a half-metal with the magnetic moment of 2.0 micro(B), and Co-doped BN sheet becomes a narrow-gap semiconductor with a magnetic moment of 1.0 micro(B). However, no magnetic moment is induced on a Ni-doped BN sheet, which has the same band gap as a pristine BN sheet. Furthermore, Fe atom easily forms an isolated particle on the BN sheet, while Ni and Co atoms are likely to form a sheet-supported metal nanotemplate. These results are useful for spintronics application and could help in the development of magnetic nanotructures and metallic nanotemplate at room temperature.

Effects of stacking periodicity on the electronic and optical properties of GaAs/AlAs superlattice: a first-principles study.

The effects of stacking periodicity on the electronic and optical properties of GaAs/AlAs superlattice have been explored by density functional theory calculations. Among the (GaAs)m/(AlAs)m, (GaAs)1/(AlAs)m and (GaAs)m/(AlAs)1 (m = 1 to 5) superlattices, the band gaps of (GaAs)m/(AlAs)1 superlattices decrease significantly as the layer of GaAs increases, and the cut-off wavelengths are found to locate in the near infrared region. For (GaAs)m/(AlAs)1 SLs, the conduction bands shift toward Fermi level, resulting in the smaller band gap, while conduction bands of (GaAs)1/(AlAs)n SLs slightly shift to higher energy, which lead to comparable band gaps. The layer number of GaAs shows negligible effects on the reflectivity spectra of superlattice structures, while the absorption coefficient shows a red-shift with the increasing layer of GaAs, which is beneficial for the application of GaAs/AlAs superlattice in the field of near infrared detector. These results demonstrate that controlling the number of GaAs layers is a good method to engineer the optoelectronic properties of GaAs/AlAs superlattice.

Ab initio molecular dynamics simulation of a pressure induced zinc blende to rocksalt phase transition in SiC.

The high-pressure induced phase transformation from the zinc blende to rocksalt structure in SiC has been studied by the ab initio molecular dynamics method. The simulations showed that SiC passes through a tetragonal intermediate state before transforming to a monoclinic phase at 160 GPa. The mechanism for this phase transformation agrees well with recent ab initio MD simulations, in which the applied pressure was as high as ∼600 GPa, but in the present study the transformation occurs at much lower pressure.

Correlation between HSD17B4 expression in rat liver cancer tissues and inflammation or proliferation.

OBJECTIVE: Pathogenesis and progression of liver cancer are correlated with inflammatory response and estrogen level. 17ß-estradiol dehydrogenase IV (HSD17B4) is highly expressed in human liver cancer tissues. HSD17B4 participates in liver cancer cell proliferation via suppressing estradiol (E2) activity. This study generated a rat liver cancer model, on which the correlations between HSD17B4 and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), proliferating cell nucleus antigen (PCNA) expression were analyzed. MATERIALS AND METHODS: Male Sprague Dawley (SD) rats were randomly assigned into control and model group (N=30). Diethylnitrosamine was used to induce liver cancer in a rat model. HE staining was used to observe liver injury whilst ELISA was used to measure serum TNF-α and IL-6 levels. The level of serum E2 was quantified by radioimmunoassay. Serum liver function indexes were measured by automatic biochemical analyzer. Protein expressions of HSD17B4, p-Akt, p-ERK and PCNA were measured by Western blot. RESULTS: The inflammatory infiltration and necrosis of hepatocytes were shown in model group by HE staining, along with aggravated liver indexes. Significantly high phosphorylation level of Akt and ERK, along with the increase of HSD17B3 and PCNA expressions, was found in model group (p<0.05 compared to control group). Serum E2 level was statistically decreased, whilst TNF-α and IL-6 were up-regulated (p<0.05). HSD17B4 was positively correlated with TNF-α, IL-6 and PCNA expressions (r=0.68, 0.62 and 0.56, p<0.05). CONCLUSIONS: HSD17B4 is over-expressed in rat liver cancer tissues. Its expression was positively correlated with TNF-α, IL-6 and PCNA levels, and probably participates in liver cancer cell proliferation via ERK and Akt signal pathway.

A comparative study of low energy radiation response of AlAs, GaAs and GaAs/AlAs superlattice and the damage effects on their electronic structures.

In this study, the low energy radiation responses of AlAs, GaAs and GaAs/AlAs superlattice are simulated and the radiation damage effects on their electronic structures are investigated. It is found that the threshold displacement energies for AlAs are generally larger than those for GaAs, i.e., the atoms in AlAs are more difficult to be displaced than those in GaAs under radiation environment. As for GaAs/AlAs superlattice, the Ga and Al atoms are more susceptible to the radiation than those in the bulk AlAs and GaAs, whereas the As atoms need comparable or much larger energies to be displaced than those in the bulk states. The created defects are generally Frenkel pairs, and a few antisite defects are also created in the superlattice structure. The created defects are found to have profound effects on the electronic properties of GaAs/AlAs superlattice, in which charge transfer, redistribution and even accumulation take place, and band gap narrowing and even metallicity are induced in some cases. This study shows that it is necessary to enhance the radiation tolerance of GaAs/AlAs superlattice to improve their performance under irradiation.

A comparative study of the mechanical and thermal properties of defective ZrC, TiC and SiC.

ZrC and TiC have been proposed to be alternatives to SiC as fuel-cladding and structural materials in nuclear reactors due to their strong radiation tolerance and high thermal conductivity at high temperatures. To unravel how the presence of defects affects the thermo-physical properties under irradiation, first-principles calculations based on density function theory were carried out to investigate the mechanical and thermal properties of defective ZrC, TiC and SiC. As compared with the defective SiC, the ZrC and TiC always exhibit larger bulk modulus, smaller changes in the Young's and shear moduli, as well as better ductility. The total thermal conductivity of ZrC and TiC are much larger than that of SiC, implying that under radiation environment the ZrC and TiC will exhibit superior heat conduction ability than the SiC. One disadvantage for ZrC and TiC is that their Debye temperatures are generally lower than that of SiC. These results suggest that further improving the Debye temperature of ZrC and TiC will be more beneficial for their applications as fuel-cladding and structural materials in nuclear reactors.