Prediction of pathological activity in Crohn's disease based on dual-energy CT enterography.

PURPOSE: To explore the feasibility of predicting the pathological activity of Crohn's disease (CD) based on dual-energy CT enterography (DECTE). METHODS: The clinical, endoscopic, imaging and pathological data of 55 patients with CD scanned by DECTE were retrospectively analyzed; the pathological results were used as a reference standard to classify the diseased bowel segments into active and inactive phases. The normalized iodine concentration (NIC), energy-spectrum curve slope K, dual energy index (DEI), fat fraction (FF) of the arterial phases and venous phases were compared. To assess the parameters' predictive ability, receiver-operating characteristic curves were used. The Delong test was used to compare the differences between the diagnostic efficiency of each parameter. RESULTS: A total of 84 intestinal segments were included in the study, including 54 active intestinal segments and 30 inactive intestinal segments. The NIC, energy-spectrum curve slope K and DEI were significantly different between active and inactive bowel segments in the arterial and venous phases (P < 0.05), while FF were not significantly different (P > 0.05). The largest area under the curve (AUC) of NIC, energy-spectrum curve slope K and DEI were higher in arterial phase than in venous phase. For identifying the intestinal activity of CD, the maximum AUC of NIC in arterial phase was 0.908, with a sensitivity of 0.833 and a specificity of 0.800, and the DEI in arterial phase had the highest sensitivity (0.944). CONCLUSION: The NIC, energy-spectrum curve slope K and DEI can effectively distinguish the active and inactive phases of the intestinal segments of CD patients and provide good assistance for determining further treatment.

Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

A preliminary study on analysis of lower limb energy during walking in the patients with knee replacement.

Background: Knee replacement surgeries are used to reduce pain and enhance functionality for individuals with knee arthritis. It is predicted that the annual volume of total knee replacement surgeries conducted in the US will surge by a substantial 673% by 2030. Though a lot of studies have done gait analysis on patients with knee replacement, little research is on energy changes in the lower limbs during gait. This study aimed to investigate the mechanical energy changes in the lower limbs for patients with total knee arthroplasty (TKA) and unicondylar knee arthroplasty (UKA), and ultimately to provide a specific tool to analyze limb energy during gait in clinical practice. Methods: 10 TKA and 8 UKA patients were recruited for gait analysis. The control group consisted of 11 individuals without knee replacement surgery. Vicon motion capture system and Plug-in-Gait model were used to collect gait data to obtain marker coordinates and gait parameters. The kinetic energy, potential energy, and rotational energy for each segment in the lower limbs were calculated. The energies in the centre of pelvis were considered as the approximate to the centre of mass. The energy recovery coefficients were analysed for each segment during gait. SPSS was used to identify the differences between different groups. Results: The results showed that during walking, the upper leg had the highest recovery coefficient, approximately 40%, followed by the foot at 10%, and the lowest recovery coefficient was observed in the lower leg, approximately 1-3%. However, the energy recovery coefficients at the centre of pelvis were significantly higher in the control group than the TKA and UKA groups by roughly 12%-15%. Conclusions: The energy difference between the operative and non-operative sides is not significant regardless of the type of surgery. The TKA and UKA groups were more active in potential energy than control group. The upper leg has the highest recovery efficiency of kinetic and potential energy exchanges when walking. The control group used the energy for whole body is better than the patient groups. This study provides a new and useful way to analyze mechanical energy in the lower limbs during gait and could be applied in clinical practice.

Design of hollow mesoporous TiO2@BiOBr/Bi4O5Br2 type-II/Z-scheme tandem heterojunctions under confinement effect: Improved space charge separation and enhanced visible-light photocatalytic performance.

The new type of hollow mesoporous TiO2@BiOBr/Bi4O5Br2 type-II/Z-scheme tandem heterojunction is synthesized using MIL-125(Ti) as the precursor based on the confinement effect caused by the outward shrinkage induced by the interface. Among them, the BiOBr shell is an indispensable component of forming a cavity during the pyrolysis of MIL-125(Ti). Not only that, BiOBr is partially converted into Bi-rich Bi4O5Br2 at high temperature, and the remaining BiOBr acts as a bridge to connect TiO2 and Bi4O5Br2 to construct a type-II/Z-scheme tandem heterojunction. This new type of hollow mesoporous tandem heterojunction shows excellent degradation efficiency (95%) for 10 mg/L ciprofloxacin (CIP) within 40 min, with a rate constant (K) of 0.05930 min-1. The Fukui index is used to determine the attack site of CIP, and the possible degradation pathway is proposed through LC-MS analysis. The results of the culture of Vibrio qinghaiensis-Q67 showed that ciprofloxacin and its intermediate products have biological toxicity, and the toxicity is reduced with the progress of photodegradation. This method of synthesizing novel hollow mesoporous TiO2@BiOBr/Bi4O5Br2 type-II/Z-scheme tandem heterojunctions based on the confinement effect will provide a new idea for other use of MOF to synthesize hollow and high-efficiency heterojunctions.

Tracking the evolution of untreated high-intermediate/high-risk diffuse large B-cell lymphoma by circulating tumour DNA.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogenous malignancy, early identification of patients for relapse remains challenging. The potential to non-invasively monitor tumour evolutionary dynamics of DLBCL needs to be further established. In the present study, 17 tumour biopsy and 38 plasma samples from 38 patients with high-intermediate/high-risk DLBCL were evaluated at baseline. Longitudinal blood samples were also collected during therapy. Circulating tumour DNA (ctDNA) was analysed using targeted sequencing based on a gene panel via a recently developed methodology, circulating single-molecule amplification and re-sequencing technology (cSMART). We found that the most frequently mutated genes were tumour protein p53 (TP53; 42·1%), histone-lysine N-methyltransferase 2D (KMT2D; 28·9%), caspase recruitment domain family member 11 (CARD11; 21·1%), cAMP response element-binding protein binding protein (CREBBP; 15·8%), ß2 -microglobulin (B2M; 15·8%), and tumour necrosis factor alpha-induced protein 3 (TNFAIP3; 15·8%). The mutation profiles between ctDNA and matched tumour tissue showed good concordance; however, more mutation sites were detected in ctDNA samples. Either TP53 or B2M mutations before treatment predicted poor prognosis. Analysis of dynamic blood samples confirmed the utility of ctDNA for the real-time assessment of treatment response and revealed that the increases in ctDNA levels and changes in KMT2D mutation status could be useful predictors of disease progression. Our present results suggest that ctDNA is a promising method for the detection of mutation spectrum and serves as a biomarker for disease monitoring and predicting clinical recurrence.

Plasma EGFR mutation abundance affects clinical response to first-line EGFR-TKIs in patients with advanced non-small cell lung cancer.

BACKGROUND: Activated epidermal growth factor receptor (EGFR) mutation is the main pathogenic cause of non-small cell lung cancer (NSCLC) in Asia. However, the impact of plasma EGFR mutation abundance, especially of the ultra-low abundance of EGFR mutation detected by highly sensitive techniques on clinical outcomes of first-line EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients remains unclear. METHODS: We qualitatively detected baseline EGFR status of NSCLC tissues using amplification-refractory mutation system and quantified the plasma abundance of EGFR mutations through next-generation sequencing (NGS). Every 8-12 weeks, we performed dynamic detection of plasma mutation abundance and imaging evaluation. We analyzed the association between plasma abundance of EGFR sensitizing mutations, tumor size, tumor shrinkage percentage, concomitant TP53 mutations, and clinical response to TKIs. RESULTS: This prospective study enrolled 135 patients with advanced NSCLC. The objective response rate (ORR) and disease control rate (DCR) for EGFR mutation-positive patients were 50.0% and 87.0%, respectively. When the cutoff value of plasma EGFR mutation abundance was 0.1%, the ORRs of TKI-treated patients were significantly different (60.0% for the >0.1% group vs. 21.4% for the ≤0.1% group, P=0.028). Median progression-free survival (PFS) was significantly longer for participants with a mutation abundance above 0.1% compared to those with a 0.01-0.1% abundance (log rank, P=0.0115). There was no significant association between plasma abundance of EGFR sensitizing mutations and tumor size, tumor shrinkage percentage, or concomitant TP53 mutations. Cox multivariate analysis demonstrated that plasma mutation abundance was an independent predictive factor for PFS [hazard ratio (HR) 2.41, 95% confidence interval (CI): 1.12-5.20; P=0.025]. We identified 11 participants with the acquired T790M resistance mutation according to serial dynamic plasma samples. CONCLUSIONS: Liquid biopsy screening based on highly sensitive NGS is reliable for detecting drug resistance and actionable somatic mutations. The plasma abundance of the EGFR driver mutation affected clinical response to EGFR-TKIs in advanced NSCLC patients; prolongation of PFS was also observed in patients with an ultra-low abundance of EGFR sensitizing mutations.

Predictive Value of Early Response to Chemoradiotherapy in Advanced Esophageal Squamous Cell Carcinoma by Diffusion-Weighted MR Imaging.

OBJECTIVE: To explore the value of diffusion-weighted imaging for early response detection of locally advanced esophageal squamous cell carcinoma with concurrent chemoradiotherapy. METHODS: Fifty-five (42 males, 13 females) patients with locally advanced esophageal cancer who were undergoing chemoradiotherapy were recruited for this study. Diffusion-weighted imaging was performed in all patients before therapy, at the first weekend, the second weekend, and the end of chemoradiotherapy. The rate of change in apparent diffusion coefficient value and the maximum diameter between pretherapy and posttherapy were calculated. RESULTS: Fifty-five patients with locally advanced esophageal squamous cell carcinoma were classified as responders (40 cases) and nonresponders (15 cases). Before chemoradiotherapy, the responders group had a significantly lower apparent diffusion coefficient values than the nonresponders group (t = -4.815, P = .000). At the 3 time points after chemoradiotherapy (first weekend, second weekend, and the end of chemoradiotherapy), there was no statistically significant difference in apparent diffusion coefficient values between responders and nonresponders (P > .05). The responders group had a significantly higher rate of change in apparent diffusion coefficient value than the nonresponders group at each time point (P < .05). At the first weekend of chemoradiotherapy, the rate of change in the maximum diameter was not significantly different in the 2 groups (t = 0.928, P = .357). There was a negative correlation between the tumor apparent diffusion coefficient value of pretherapy and the reduction ratio of tumor maximum diameter at the end of chemoradiotherapy (r = -0.592, P = .000). CONCLUSIONS: The change rate of apparent diffusion coefficient value by the end of the first week after beginning chemoradiotherapy may be a sensitive indicator to detect the early response to locally advanced esophageal squamous cell carcinoma.

Parallel Speciation of Wild Rice Associated with Habitat Shifts.

The occurrence of parallel speciation strongly implies the action of natural selection. However, it is unclear how general a phenomena parallel speciation is since it was only shown in a small number of animal species. In particular, the adaptive process and mechanisms underlying the process of parallel speciation remain elusive. Here, we used an integrative approach incorporating population genomics, common garden, and crossing experiments to investigate parallel speciation of the wild rice species Oryza nivara from O. rufipogon. We demonstrated that O. nivara originated multiple times from different O. rufipogon populations and revealed that different O. nivara populations have evolved similar phenotypes under divergent selection, a reflection of recurrent local adaptation of ancient O. rufipogon populations to dry habitats. Almost completed premating isolation was detected between O. nivara and O. rufipogon in the absence of any postmating barriers between and within these species. These results suggest that flowering time is a "magic" trait that contributes to both local adaptation and reproductive isolation in the origin of wild rice species. Our study thus demonstrates a convincing case of parallel ecological speciation as a consequence of adaptation to new environments.

Percutaneous Kyphoplasty for the Treatment of Osteoporotic Vertebral Fractures With Intravertebral Fluid or Air: A Comparative Study.

STUDY DESIGN: A retrospective comparative study. OBJECTIVE: To compare the characteristics of osteoporotic vertebral fractures (OVFs) with intravertebral fluid (IVF) and those with intravertebral air (IVA), and the efficacy of percutaneous balloon kyphoplasty (PKP) in treating OVFs with these 2 different intravertebral components. SUMMARY OF BACKGROUND DATA: Previous studies have focused on the efficacy of percutaneous vertebroplasty (PVP) and PKP in treating OVFs with intravertebral cleft. However, no prior studies investigated the impact of the different components of cleft on the therapeutic effect of PVP or PKP. METHODS: On the basis of the presence of IVF or IVA signal on preoperative MR images, 22 patients were classified into IVF group and 13 patients into IVA group. The characteristics of patients with IVF and those with IVA were compared. The anterior and middle heights of the involved vertebrae, the kyphotic angles, the Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI) scores were recorded preoperatively, 1 day after surgery, and at last follow-up. RESULTS: Severe collapse of involved vertebrae (P=0.024) and the gap appearance of clefts (P=0.004) were significantly more common in IVA group than in IVF group. The vertebral heights, the local kyphotic angles, the VAS, and ODI scores were all significantly improved after PKP in both groups. However, the vertebral height restoration and kyphotic deformity correction were more significant in IVF group than in IVA group (P<0.001). No significant differences regarding VAS and ODI scores were detected between the 2 groups at each follow-up time. CONCLUSIONS: PKP is an effective treatment strategy for both OVFs with IVF and with IVA, whereas vertebral height restoration and kyphotic deformity correction are much more significant in vertebrae with IVF. Presence of IVA without fluid filling-in on MR images may indicate an advanced stage of intravertebral osteonecrosis.

Adjacent disc height reduction and clinical outcome after intradiscal cement leakage.

OBJECTIVE: The purpose of this study is to evaluate the effect of intradiscal cement leakage on the height of adjacent cement-containing discs and the resulting clinical efficacy after kyphoplasty. METHODS: A total of 124 patients were included and classified into two groups: group A included 20 patients with intradiscal leakage, and group B contained 104 patients without intradiscal leakage. The mean follow-up time was 20.56±3.51 months. The height of the corresponding discs in both groups was measured using Farfan's method. Clinical efficacy was assessed using the Visual Analog Scale and Oswestry Disability Index scores at each follow-up time. RESULTS: The anterior disc height, posterior disc height and Farfan Index significantly decreased in both groups at last follow-up. The disc height reduction was 9.19±2.89% in group A and 3.88±2.70% in group B, which was significantly different between the groups (P<0.01). The disc height reduction rate was 29.39±7.90% in group A and 12.75±8.18% in group B, which was also a statistically significant difference (P<0.01). The VAS and ODI scores improved significantly after surgery and maintained at last follow-up, and there was no statistically significant difference between Groups A and B. CONCLUSION: Intradiscal cement leakage was associated with the degeneration of cement-containing disc but did not reduce the clinical efficacy at early stages.

Population genetic structure of Oryza rufipogon and Oryza nivara: implications for the origin of O. nivara.

Ecological speciation plays a primary role in driving species divergence and adaptation. Oryza rufipogon and Oryza nivara are two incipient species at the early stage of speciation with distinct differences in morphology, life history traits and habitat preference, and therefore provide a unique model for the study of ecological speciation. However, the population genetic structure of the ancestral O. rufipogon has been controversial despite substantial study, and the origin of the derivative O. nivara remains unclear. Here, based on sequences of 10 nuclear and two chloroplast loci from 26 wild populations across the entire geographic ranges of the two species, we conducted comprehensive analyses using population genetics, phylogeography and species distribution modelling (SDM) approaches. In addition to supporting the two previously reported major subdivisions, we detected four genetically distinct groups within O. rufipogon and found no correlation between the genetic groups and either species identity or geographical regions. The SDM clearly showed substantial change in the distribution range of O. rufipogon in history, demonstrating that the repeated extinction and colonization of local populations due to multiple glacial-interglacial cycles during the Quaternary was most likely the main factor shaping the confounding population genetic structure of O. rufipogon. Moreover, we found significant differences between the two species in climate preferences, suggestive of an important role for climatic factors in the adaptation, persistence and expansion of O. nivara. Finally, based on the genetic pattern and dynamics of the O. nivara populations, we hypothesize that O. nivara might have independently originated multiple times from different O. rufipogon populations.

Factors affecting recompression of augmented vertebrae after successful percutaneous balloon kyphoplasty: a retrospective analysis.

BACKGROUND: The instantaneously recovered stability and strength following vertebral augmentation prevent continuous micro-motion and further collapse of fractured vertebrae. Despite this, during follow-up of our patients, we observed recompression of augmented vertebrae with significant vertebral height loss and aggravation of local kyphotic deformity. PURPOSE: To identify the risk factors related to recompression and to evaluate the clinical significance of recompression. MATERIAL AND METHODS: One hundred and twenty-one patients who underwent single-level kyphoplasty for osteoporotic vertebral fractures were retrospectively analyzed and classified into the following two groups: group 1 with recompression and group 2 without recompression. Characteristics of patients and fractured vertebrae were compared between the two groups. Univariate and multivariate regression analyses were performed to identify risk factors for recompression. We evaluated the visual analogue scale (VAS) and the Oswestry disability index (ODI) scores in both groups to elucidate the clinical impact. RESULTS: During an average of 20.75 ± 4.43 months of follow-up, 17 augmented vertebrae developed recompression. In the recompression group, vertebral height loss was accompanied by significantly aggravated local kyphotic deformity. The local kyphotic angle differed significantly between the two groups at final follow-up (P = 0.011). However, the VAS and ODI scores were maintained at final follow-up in both groups although the values were slightly higher in group 1. Solid lump distribution pattern (OR = 8.718; P = 0.003) and the degree of vertebral height restoration (OR = 1.260; P < 0.001) were identified as the most important risk factors for recompression. CONCLUSION: Fractured vertebrae containing solid lump cement and those with more vertebral height restoration are at higher risk of recompression. More attention should be given to these patients considering the aggravated local kyphotic deformity.

Structural and optical characterizations of InPBi thin films grown by molecular beam epitaxy.

InPBi thin films have been grown on InP by gas source molecular beam epitaxy. A maximum Bi composition of 2.4% is determined by Rutherford backscattering spectrometry. X-ray diffraction measurements show good structural quality for Bi composition up to 1.4% and a partially relaxed structure for higher Bi contents. The bandgap was measured by optical absorption, and the bandgap reduction caused by the Bi incorporation was estimated to be about 56 meV/Bi%. Strong and broad photoluminescence signals were observed at room temperature for samples with xBi < 2.4%. The PL peak position varies from 1.4 to 1.9 µm, far below the measured InPBi bandgap.

Isolation and characterization of microsatellite loci for a bioenergy grass, Miscanthus sacchariflorus (Poaceae).

PREMISE OF THE STUDY: Microsatellite loci were developed for the biomass C4 grass, Miscanthus sacchariflorus, and proved to be suitable markers for population genetic studies and germplasm management of this species. • METHODS AND RESULTS: Twenty-three polymorphic microsatellite loci were identified from an enriched genomic library of M. sacchariflorus. The polymorphism was assessed in 50 individuals from two populations in China. The number of alleles per locus varied from two to 18, with a mean of 8.13. The observed and expected heterozygosities ranged from 0.2 to 1.0 and from 0.198 to 0.898, respectively. • CONCLUSIONS: These new markers will be useful for further investigation of genetic diversity and population genetic structure as well as molecular breeding of Miscanthus species.

Development of microsatellite markers for Miscanthus sinensis (Poaceae) and cross-amplification in other related species.

PREMISE OF THE STUDY: We developed microsatellite loci for the biomass crop Miscanthus sinensis to investigate genetic diversity and population structure of M. sinensis and its closely related species. METHODS AND RESULTS: Fourteen microsatellite loci were identified from an enriched genomic library of M. sinensis and tested in one M. sinensis population. The number of alleles per locus ranged from 1 to 15, with a mean of 7.0. The observed and expected heterozygosities varied from 0.318 to 0.864 and from 0.424 to 0.901, respectively. Of them, 12 primers could be applied to three other species in Miscanthus (M. sacchariflorus, M. floridulus, and M. lutarioriparius). CONCLUSIONS: These markers will be important for further analyzing population genetics and evolutionary history, as well as facilitating molecular breeding of Miscanthus sinensis and its related species.

Contrasting population genetic structure and gene flow between Oryza rufipogon and Oryza nivara.

The cross compatible wild relatives of crops have furnished valuable genes for crop improvement. Understanding the genetics of these wild species may enhance their further use in breeding. In this study, sequence variation of the nuclear Lhs1 gene was used to investigate the population genetic structure and gene flow of Oryza rufipogon and O. nivara, two wild species most closely related to O. sativa. The two species diverge markedly in life history and mating system, with O. rufipogon being perennial and outcrossing and O. nivara being annual and predominantly inbreeding. Based on sequence data from 105 plants representing 11 wild populations covering the entire geographic range of these wild species, we detected significantly higher nucleotide variation in O. rufipogon than in O. nivara at both the population and species levels. At the population level the diversity in O. rufipogon (Hd = 0.712; theta (sil) = 0.0017) is 2-3 folds higher than that in O. nivara (Hd = 0.306; theta (sil) = 0.0005). AMOVA partitioning indicated that genetic differentiation among O. nivara populations (78.2%) was much higher than that among O. rufipogon populations (52.3%). The different level of genetic diversity and contrasting population genetic structure between O. rufipogon and O. nivara might be explained by their distinct life histories and mating systems. Our simulation using IM models demonstrated significant gene flow from O. nivara to O. rufipogon, indicating a directional introgression from the annual and selfing species into the perennial and outcrossing species. The ongoing introgression has played an important role in shaping current patterns of genetic diversity of these two wild species.

Microsatellite analysis of genetic diversity and population genetic structure of a wild rice (Oryza rufipogon Griff.) in China.

Genetic diversity and population genetic structure of natural Oryza rufipogon populations in China were studied based on ten microsatellite loci. For a total of 237 individuals of 12 populations collected from four regions, a moderate to high level of genetic diversity was observed at population levels with the number of alleles per locus ( A) ranging from 2 to 18 (average 10.6), and polymorphic loci ( P) from 40.0% to 100% (average 83.3%). The observed heterozygosity ( H(O)) varied from 0.163 to 0.550 with the mean of 0.332, and the expected heterozygosity ( H(E)) from 0.164 to 0.648 with the mean of 0.413. The level of genetic diversity for Guangxi was the highest. These results are in good agreement with previous allozyme and RAPD studies. However, it was unexpected that high genetic differentiation among populations was found ( R(ST) = 0.5199, theta = 0.491), suggesting that about one-half of the genetic variation existed between the populations. Differentiation (pairwise theta) was positively correlated with geographical distance ( r = 0.464), as expected under the isolation by distance model. The habitat destruction and degradation throughout the geographic range of O. rufipogon may be the main factor attributed to high genetic differentiation among populations of O. rufipogon in China.