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Background: X-linked lymphoproliferative disease (XLP) is a rare primary immunodeficiency disorder. We performed experiments based on two strategies of preimplantation genetic testing (PGT) for a family with XLP caused by a mutation in SH2D1A (c.191G > A)., Methods: First, a single-cell polymerase chain reaction (PCR) protocol was established using single lymphocytes. A nested PCR experiment was performed with direct sequencing after whole genome amplification of single cells to assess the accuracy of the genetic diagnosis. Embryos obtained after intracytoplasmic sperm injection were biopsied on day 3 and detected using the established single-cell PCR protocol. In the second PGT cycle, targeted next generation sequencing (NGS) was performed and the single nucleotide polymorphism (SNP) markers flanking SH2D1A were selected to determine the disease-carrying haplotype phase in each embryo., Result: In the first PGT cycle, six embryos were biopsied. Discounting an embryo from a single failed PCR experiment, five embryos were identified, including three unaffected and two hemizygous. After PCR, one normal embryo was transferred when it was developing into an early blastocyst. Although the ultrasound images indicated a viable singleton pregnancy, the implantation was on the cesarean scar. Therefore, an artificial abortion was performed. In the haplotyping cycle, six embryos were identified to have inherited a haplotype without pathogenic mutations. After the embryo implantation process failed twice, a successful singleton pregnancy was established, and subsequently, a healthy female child was born., Conclusion: Targeted NGS with haplotyping analysis circumvents the laborious process of multiplex PCR and is more likely to ensure diagnostic accuracy. However, when a genetic recombination occurs close to the site of mutation, confirmed identification using selected SNP markers can be challenging., (Copyright © 2020 Chen, Shi, Qian, Wang, Zhang, Li, Chen, Chang, Fei, Zhang, Huang and Xu.)

Background: Adult acquired flatfoot deformity (AAFD) is a complex 3-dimensional pathology characterized by peritalar subluxation (PTS) of the hindfoot. For many years, PTS was measured at the posterior facet of the subtalar joint. More recently, subluxation of the middle facet has been proposed as a more accurate and reliable marker of symptomatic AAFD, enabling earlier detection. The objective of this study was to compare the amount of subluxation between the medial and posterior facets in patients with AAFD., Methods: In this institutional review board-approved retrospective comparative study, a total of 76 patients with AAFD (87 feet) who underwent standing weightbearing computed tomography (WBCT) as a standard baseline assessment of their foot deformity were analyzed. Two blinded fellowship-trained orthopedic foot and ankle surgeons with >10 years of experience measured subtalar joint subluxation (as a percentage of joint uncoverage) at the both posterior and middle facets. One of the readers also measured the foot and ankle offset (FAO). PTS measurements were performed at the sagittal midpoint of the articular facets using coronal plane WBCT images. Intra- and interobserver agreement was measured for PTS measurements using the intraclass correlation coefficient (ICC). The intermethod agreement between the posterior and middle facet subluxation was assessed using Spearman's correlation and bivariate analysis. Paired comparison of the measurements was performed using the Wilcoxon test. A multivariate analysis and a partition prediction model were used to assess influence of PTS measurements on FAO values. P values of <.05 were considered significant., Results: ICCs for intra- and interobserver reliabilities were 0.97 and 0.93, respectively, for posterior and 0.99 and 0.97, respectively, for middle facet subluxation. The intermethod Spearman's correlation between subluxation of the posterior and middle facets was measured at 0.61. In a bivariate analysis, both measurements were found to be significantly and linearly correlated ( P < .0001; R 2 = 0.42). Measurements of middle facet subluxation were found to be significantly higher than those for posterior facet subluxation, with a median difference (using the Hodges-Lehman factor) of 17.7% ( P < .001; 95% CI, 10.9%-23.6%). We also found that for every 1% increase in posterior facet subluxation there was a corresponding 1.6-fold increase in middle facet subluxation. Only middle facet subluxation measurements were found to significantly influence FAO calculations ( P = .003). The partition prediction model demonstrated that a middle facet subluxation value of 43.8% represented an important threshold for increased FAO., Conclusion: This study is the first to compare WBCT measurements of subtalar joint subluxation at the posterior and middle facets as markers of PTS in patients with AAFD. We found a positive linear correlation between the measurements, with subluxation of the middle facet being significantly more pronounced than that of the posterior facet by an average of almost 18%. This suggests that middle facet subluxation may provide an earlier and more pronounced marker of progressive PTS in patients with AAFD., Level of Evidence: Level III, retrospective comparative cohort study.

Coal-dominated winter heating practices in China are largely accepted to be a leading cause of winter haze in the region though the amount of coal for heating is actually much lower than for power generation or industrial process. However, little is known about how the total rural coal weight in a region could be attributed to real time (e.g., daily) patterns, limiting the understanding of dynamic impacts of coal emissions and the adoption of timely measures against predicted haze. Considering that winter heating essentially protects against cold temperatures, coal burning strength may be related to the temperatures that people experience. A field study was organized to test the validity of this hypothesis. A system was designed to continuously monitor every instance of coal addition, and coal consumption on any given day for a whole village (W DAY ) was calculated by summating all the additions. Meanwhile, a new term, composite temperature (T COM ), which incorporates a few weather-related elements, was introduced to represent cold temperatures that individuals experience. It was found that W DAY and T COM presented opposite variations, and a negative linear correlation was observed (W DAY  = -0.75T COM  + 11.86, R 2  = 0.75), revealing the feasibility of estimating coal consumption on a certain day (W DAY ) based on weather data (T COM ) for a given village. An extensive form of the algorithm for any area of interest (e.g., a district, city, or province) can be expressed as W DAY  = (-0.75T COM  + 11.86)‧N H /834, where N H denotes the number of households in a region. This algorithm reflects the essence of winter heating (to resist cold temperatures), and therefore its logic is highly likely to be useful for any countries of the world regardless of what forms of energy used (coal or other energy forms) provided the energy involved is unexceptionally used for winter heating, though there may be some uncertainties in estimated coal consumption due to multiple factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The development of an economic, environmental-friendly and energy-saving process for the selective depolymerization of lignin is an outstanding challenge. Herein, a novel and efficient visible-light-induced photocatalytic process for the selective depolymerization of lignin model compounds and organosolv lignin was first developed by using perylene diimide (PDI) as a metal-free organocatalyst. Interestingly, it can completely decompose the oxidized lignin models to phenolic and ketone fragmentation molecules with very high selectivity at room temperature under visible light illumination. Furthermore, the use of a home-made photocatalytic continuous-flow reactor efficiently shortened the reaction time within an hour. Even for organosolv lignin, nearly 86% mass ratio of lignin was degraded to low-molecular-mass monoaromatic or diaromatic products. We found that superior performances were realized by single-electron transfer (SET) from the photoexcited strongly reducing PDI˙ - anion to the ketone groups of the β-O-4 linkage in the lignin.

Background: Intractable hallucal ganglion cysts (HGCs) are often a symptomatic and recurrent condition. Its connection with the ankle joint is not well understood. Our aim was to evaluate the relationship between tenosynovitis of the flexor hallucis longus (FHL) tendon at the level of the ankle with formation of an HGC. In addition, we sought to analyze the outcomes of cyst excision combined with ankle capsulorrhaphy., Methods: Nineteen patients with HGC who underwent surgical intervention were included between June 2016 and June 2019. Eight had known recurrences. Ankle arthrography and cyst excision were performed on all patients. Clinical evaluations included the American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS), and evaluation of postoperative complications. The mean follow-up period was 16.5 ± 8.6 months., Results: Thirteen of the 19 HGCs (68.4%) had a connection with the FHL tendon sheath. Combined with ankle capsulorrhaphy, there was no recurrence after cyst excision. The VAS score decreased from 2.1 ± 1.5 to 0.4 ± 0.8, and AOFAS score significantly improved from 84.3 ± 8.7 to 97.4 ± 5.2 at final follow-up ( P < .001)., Conclusions: Most of these patients had a connection between the HGC and ankle joint. Ankle arthrography appeared to be useful for diagnosis, and cyst excision combined with ankle capsulorrhaphy was an effective treatment without cyst recurrence., Level of Evidence: Level IV, case series.

The severe foot and ankle deformities the authors' organization has encountered in humanitarian programs worldwide are more complicated than those surgeons treat in daily practice in developed countries. Severity of deformity, patients' economic limitations, patients' expectations and realistic needs in life, availability of surgical instrumentation, the local team's understanding of foot and ankle surgery and their ability to do consultation for patients postoperatively, and compliance of patients all account for success of the surgery. Regardless of the effort surgeons make, complications and recurrence occur. Educating and training local surgeons to take over medical care are the most important goals of the programs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies., (© 2020 The Authors. Cell Biochemistry and Function published by John Wiley & Sons Ltd.)

Objective: Our study aimed to construct a robust long non-coding RNA (lncRNA) prognostic signature for colorectal cancer (CRC) metastasis. Methods: Differentially expressed lncRNAs were identified between metastatic CRC and non-metastatic CRC samples from The Cancer Genome Atlas Database (TCGA) using the edgeR package. The differentially expressed lncRNAs with prognosis of patients with CRC metastasis were identified by univariate Cox regression analysis, followed by a stepwise multivariate Cox regression model. The survminer package in R was used to identify the optimal cutoff point for high-risk and low-risk groups. The receiver operating characteristic (ROC) curves were plotted to assess this signature. To explore potential signaling pathways associated with these lncRNAs, Gene Set Enrichment Analysis (GSEA) was performed. Results: A 6-lncRNA signature was built based on the lncRNA expression profile for CRC metastasis. The optimal cutoff value was used to classify high-risk and low-risk groups using the survminer package. The high-risk groups could have poorer survival time than the low-risk groups. ROC curve result indicated that this lncRNA signature had high sensitivity and accuracy. GSEA analysis results showed that the six lncRNAs were significantly enriched in several CRC metastasis-related signaling pathways such as "cell cycle," "DNA replication," "mismatch repair," "oxidative phosphorylation," "regulation of autophagy," and "insulin signaling pathway." Conclusion: Our study constructed a 6-lncRNA model for predicting the survival outcomes of patients with CRC metastasis, which could become potential prognostic biomarkers, and therapeutic targets for CRC metastasis., (Copyright © 2020 Li, Chen, Wang, Zhang, Su and Zhang.)

The evolution of Lapidus fixation has been strongly associated with the understanding of the anatomy and function of the first tarsometatarsal joint, the mechanism of hypermobility of the first tarsometatarsal joint, and cause of the hallux valgus deformity in 3 dimensions. Some methods, such as plantar plating, nitinol staples, and intramedullary fixation, have proven to be stronger biomechanically in cadaveric testing. Theoretically, stable fixation will reduce the rate of complications, in particular, that of nonunion and allow for early postoperative weight-bearing. Further clinical studies are needed to examine whether current biomechanical studies will translate to relevant clinical outcomes., Competing Interests: Disclosure Dr S. Li has nothing to disclose. Dr M.S. Myerson is a Consultant for Paragon 28., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cerebral microbleeds (CMBs) are more prevalent in Asian populations, and have been associated with increased risk of stroke, dementia and mortality. So far, risk factors for CMBs other than hypertension were merely known. Previous studies have shown that polymorphisms at aldehyde dehydrogenase 2 ( ALDH 2) gene were independently associated with the risk of stroke. Its role in CMBs, however, remains unclear. This study aimed to evaluate the associations of ALDH 2 gene polymorphisms with CMBs in Chinese elderly., Methods: Using bio-specimen and data collected at baseline survey of the population-based Taizhou Imaging Study (TIS) (phase I), we genotyped the single nucleotide polymorphisms (SNPs) at ALDH 2 among 549 individuals aged 55-65 years, and rs671 was used as surrogate marker of ALDH 2. CMBs were detected on brain magnetic resonance imaging (MRI), and further categorized as strictly lobar or as deep/mixed. Logistic regression models were used to evaluate the associations of the variants at ALDH 2 and CMBs., Results: CMBs were present in 103 individuals (18.8%). Forty-one point three percent participants were with ALDH 2 *2 allele and 5.1% had ALDH 2 *2/*2 genotype. Subjects with ALDH 2 *1 allele were more likely to be drinker, have hypertension or CMBs than those with *2 allele (all P<0.05). Multivariate logistic regression model showed that the ALDH 2 *1/*1 genotype was independently associated with CMBs (P=0.013), particularly for deep/mixed CMBs (P=0.008), and the association was more pronounced in men, non-drinkers or hypertension patients., Conclusions: The results suggest that Han Chinese with ALDH 2 *1/*1 genotype may be more susceptible to CMBs than those with ALDH 2 *2 allele., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Middle facet tarsal coalition is one of the commonly seen tarsal coalitions in clinical practice that can cause pain and associated flatfoot deformity. Excision of the coalition is one of the treatment options for symptomatic cases. Although symptoms may subside in children following a period of immobilization, resection should be considered as a treatment alternative for children and adolescents because of the potential for restoration of subtalar joint movement. The indications for excision of the coalition are not consistently reported in the literature, and the procedure is not always easy to perform. In this article, we describe the steps for a successful excision of a middle facet tarsal coalition., Description: The incision is marked from 1 cm inferior to the medial malleolus, extending distally to the navicular tuberosity and inferior to the level of the posterior tibial tendon. The coalition is first located by retracting the flexor tendons and the neurovascular bundle. The bone on the surface of the coalition is gradually removed to expose the middle facet. A 2-mm guide pin and a cannulated dilator probe inserted through the sinus tarsi into the tarsal canal that exits anterior to the posterior facet help with identifying the margins of the coalition. The middle facet is then removed either partially or totally, depending on the size, shape, and location of the coalition, until the posterior facet is visualized. Following excision, bone wax is used on the exposed surfaces or fat is inserted to prevent adhesion and recurrent bone formation. If there is an associated flatfoot deformity, additional surgeries, including a medial translational osteotomy or a lateral column lengthening of the calcaneus, a Cotton osteotomy, an arthroereisis, or a calcaneus stop procedure, may be necessary., Alternatives: The alternative treatment for managing a middle facet coalition is immobilization of the foot in a boot or cast for 6 to 8 weeks to decrease pain. This will not improve the function of the hindfoot, which remains stiff, but may alleviate pain temporarily. Excision of the coalition in combination with other procedures for correction of the flatfoot is an alternative to an arthrodesis of the subtalar joint and works well in children and adolescents, particularly in those with reasonable subtalar joint flexibility. A triple arthrodesis is rarely performed for an isolated middle facet coalition, even in adults, unless there is peritalar arthritis and more severe abduction of the talonavicular joint with associated stiffness., Rationale: The rationale for excision of a middle facet tarsal coalition is to maximize the mobility of the hindfoot, in particular, the subtalar joint. The success of excision of the coalition is associated with the rigidity of the hindfoot and the presence of a flatfoot deformity. The stiffer the hindfoot and the flatter the foot, the less likely is excision of the coalition to be successful. Since the alternative to resection of a middle facet coalition is arthrodesis of the subtalar joint, one must distinguish between feet in which there is mobility, and excision is more likely to be successful, and those that are rigid, for which arthrodesis is preferable. In many feet, however, the size of the coalition is not associated with the flexibility of the hindfoot, and in an extremely rigid hindfoot, we recommend an arthrodesis, even in an adolescent patient. Rigidity increases with increasing age, and it is uncommon to excise the middle facet coalition in adult patients or in a patient in whom subtalar arthritis is evident., (Copyright © 2020 by The Journal of Bone and Joint Surgery, Incorporated.)

This paper studies the acoustic radiation force of a rigid sphere positioned in a fluid-filled cylindrical cavity with an abruptly changed cross-section. This cavity consists of a semi-infinite front tube and a coaxially connected semi-infinite rear tube with different cross-sectional area through a transverse planar junction. Considering a plane wave propagates along the cavity, the exact expression of the acoustic radiation force exerted on the sphere in the front tube is deduced. The effects of the distance between the sphere and the planar junction and the radius ratio of the front tube to the rear tube on acoustic radiation force are analyzed. Numerical results show that the distance influences the acoustic radiation force periodically. Both the distance and the radius ratio of the tubes affect the magnitude and the direction of acoustic radiation force. A finite element model about the calculation for the acoustic radiation force on the sphere in the fluid-filled cylindrical cavity with suddenly changed cross-section is built to validate the theoretical results. The comparison results between the theoretical computation and the finite element simulation are in good agreement with each other. This work can support future studies for the predictive control of a particle in the cavity which has an abruptly changed cross-section.

Thermal decomposition of hexamethyldisilane (HMDS) was studied from room temperature to 1310 K using flash pyrolysis vacuum ultraviolet single-photon ionization time-of-flight mass spectrometry (VUV-SPI-TOFMS). Decomposition pathways of HMDS and initial reaction intermediates were also investigated using density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. Unimolecular decomposition reactions of HMDS involving Si-Si and Si-C bond cleavage, as well as decomposition producing Me 4 Si and :SiMe 2 via a three-centered elimination, were determined as the initiation reactions. Me 3 SiSi(Me) 2 • , Me 4 Si, Me 3 Si • , and :SiMe 2 were major products of the initiation reactions. These initial products were apt to decompose by homolytic reactions. Me 2 Si═CH 2 , :SiMe 2 , and other silene/silylene intermediates preferred decomposing through molecular eliminations. Both homolytic and molecular elimination reactions are important in the pyrolysis of HMDS.

Several recurrent microdeletions and microduplications in the proximal, central, and distal regions of chromosomal 22q11.2 have been identified. However, due to a limited number of patients reported in the literature, highly variable clinical phenotypes, and incomplete penetrance, the pathogenicity of some microdeletions/microduplications in 22q11.2 central and distal regions is unclear. Hence, the genetic counseling and subsequent pregnancy decision are extremely challenging, especially when they are found in structurally normal fetuses. Here, we reported 27 consecutive cases diagnosed prenatally with 22q11.2 microdeletions or microduplications by chromosomal microarray analysis in our center. The prenatal ultrasound features, inheritance of the microdeletions/microduplications, and their effects on the pregnancy outcome were studied. We found that fetuses with 22q11.2 microdeletions were more likely to present with structure defects in the ultrasound, as compared with fetuses with 22q11.2 microduplications. Both the prenatal ultrasound findings and the inheritance of the microdeletions/microduplications affected the parent's decision of pregnancy. Those with structure defects in prenatal ultrasound or occurred de novo often resulted in termination of the pregnancy, whereas those with normal ultrasound and inherited from healthy parent were likely to continue the pregnancy and led to normal birth. Our study emphasized that proximal, central, and distal 22q11.2 deletions or duplications were different from each other, although some common features were shared among them. More studies are warranted to demonstrate the underlying mechanisms of different clinical features of these recurrent copy-number variations, thereby to provide more information for genetic counseling of 22q11.2 microdeletions and microduplications when they are detected prenatally.

Histone deacetylase inhibitors (HDACi) are a promising therapeutic intervention for stroke. The involvement of the anti-inflammatory effects of HDACi in their neuroprotection has been reported, but the underlying mechanisms are still uncertain. Given the post-stroke inflammation is a time-dependent process, starting with acute and intense inflammation, and followed by a prolonged and mild one, we proposed whether target the early inflammatory response could achieve the neuroprotection of HDACi? To test this hypothesis, a single dose of suberoylanilide hydroxamic acid (SAHA) (50 mg/kg), a pan HDACi, was intraperitoneally (i.p.) injected immediately or 12 h after ischemia onset in a transient middle cerebral artery occlusion (tMCAO) mouse model. Compared with delayed injection, immediate SAHA treatment provided more protection, evidenced by smaller infarction volume, and a better outcome. This protection was accompanied by suppression of pro-inflammatory cytokines and reduction of activated microglia in the early stage of post-stroke inflammation. Moreover, SAHA treatment suppressed M1 cytokine expression (IL-6, TNF-α, and iNOS) while promoted the transcription of M2 cytokines (Arg-1 and IL-10) in LPS-challenged mouse microglia, and enhanced CD206 (M2 marker) but decreased CD86 (M1 markers) levels in microglia isolated from the ipsilateral hemisphere of MCAO mice. Collectively, our data suggested that the protection of SAHA on ischemic brain injury was closely associated with its inhibition on the early inflammatory response, and this inhibition was related to its reducing microglia activation and priming the activated microglia toward a more protective phenotype.

Recurrent deformity after surgical treatment of the cavus foot occurs because a procedure is not performed at the apex of the deformity. In many instances there are multiple apices and, in addition to hindfoot osteotomy or arthrodesis, the midfoot must be corrected. There is not much of a role for the Coleman block test to determine flexibility of the foot, and this has led to many failures where the foot was believed flexible and an osteotomy was insufficient treatment. Skeletal correction, even if perfect, does not last unless the foot is balanced with appropriate tendon transfers., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this paper, an expression for the acoustic radiation force on a sphere located on the axis of a zero-order Mathieu beam propagating in an ideal fluid is obtained. The simulation results of different kinds of spherical particles, including rigid spheres, fluid spheres, and elastic spheres, are presented to illustrate the theory. Curves of the acoustic radiation force function versus ka are obtained for different half-cone angles β and ellipticity parameters q of the Mathieu beam. The simulation results reveal that β and q have a direct effect on the acoustic radiation force exerted on a spherical object in an ideal fluid. The acoustic radiation force has negative values for a fluid sphere in a zero-order Mathieu beam when the half-cone angle is β≥60°. The value of the half-cone angle β also affects the direction of the acoustic radiation force for an elastic sphere. When the half-cone angle is set as a constant, the greater the ellipticity parameter is, the slower the decrease in the value of the acoustic radiation force function for a spherical particle. The conclusions of this work may be helpful for the design of acoustic tweezers and may also extend the potential applications of acoustic manipulation technology.

Objective: To evaluate the usefulness and incremental diagnostic yield of chromosomal microarray analysis (CMA) compared with standard karyotyping in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT)., Methods: A prospective cohort study and systematic review of the literature were conducted. In the prospective cohort study, 123 fetuses with CAKUT, as detected by prenatal ultrasound at our center, were enrolled and evaluated using karyotyping and CMA. In the meta-analysis, articles in PubMed and ISI Web of Knowledge databases describing copy number variations (CNVs) in prenatal cases of CAKUT were included., Results: Among the 123 fetuses in our prospective cohort study, 13 fetuses were detected with chromosomal abnormalities or submicroscopic chromosomal abnormalities by both karyotyping and CMA. In the remaining 110 fetuses, four pathogenic CNVs in four fetuses were only detected by CMA, indicating an excess diagnostic yield of 3.6%. Six publications and our own study met the inclusion criteria for the meta-analysis. In total, 615 fetuses with CAKUT were included. The pooled data from all of the reviewed studies indicate that the incremental yield of CMA over karyotyping was 3.8%., Conclusion: The use of CMA provides a 3.8% incremental yield of detecting pathogenic CNVs in fetuses with CAKUT and normal karyotype., (© 2019 John Wiley & Sons, Ltd.)

Background: Cerebral microbleeds (CMBs) are considered to be risk factors for cognitive dysfunction. The specific pathology and clinical manifestations of CMBs are different based on their locations. We investigated the association between CMBs at different locations and cognitive dysfunction and explored the potential underlying pathways in a rural Han Chinese population., Methods: We used baseline data from 562 community-dwelling adults (55-65 years old) in the Taizhou Imaging Study between 2013 and 2015. All individuals underwent multimodal brain magnetic resonance imaging (MRI) and 444 subjects completed neuropsychological tests: the Mini-Mental Status Examination and the Montreal Cognitive Assessment. Multinomial logistic regression was used to estimate the association between CMBs and cognitive dysfunction. The volume of brain regions and white matter microstructure were analyzed using Freesurfer and tract-based spatial statistics, respectively., Results: CMBs were detected in 104 individuals (18.5%) in our study. Multinomial logistic regression found deep/mixed CMBs were associated with global cognitive dysfunction (OR 3.52; 95% CI 1.21 to 10.26), whereas lobar CMBs (OR 1.76; 95% CI 0.56 to 5.53) were not. Quantification of multimodal brain MRI showed that deep/mixed CMBs were accompanied by decreased thalamic volume and loss of fractional anisotropy of bilateral anterior thalamic radiations., Conclusion: Deep/mixed CMBs were associated with cognitive dysfunction in this Chinese cross-sectional study. Disruption of thalamocortical connectivity might be a potential pathway underlying this relationship., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The revised guidelines for the management of medullary thyroid carcinoma recommend that genetic counseling regarding reproductive options, including preimplantation genetic diagnosis (PGD), be considered for all RET mutation carriers of reproductive age to avoid the transmission of multiple endocrine neoplasia type 2 (MEN2). However, the high complexity and cost of PGD have hindered its widespread use. Thus, it is necessary to establish a simple and relatively inexpensive method to facilitate the PGD of MEN2., Patients and Methods: A customized Nimblegen EZ sequence capture array was designed to capture the targeted regions, including the RET gene, and 1 Mb range on each side of the RET gene. Targeted, capture-based next-generation sequencing of three members of one family with MEN2A (the couple and the paternal father) was conducted to identify the informative markers. The diagnosis of the embryos was achieved through haplotype analysis based on informative markers and causative mutation., Results: Based on the sequencing results, 173 informative markers were detected, which were sufficient for the subsequent use for PGD. Seven informative markers and the causative mutation (RET C634Y ) were selected and subjected to Sanger sequencing. Through haplotype analysis, four embryos without inheritance of the mutation haplotype of the RET gene were diagnosed as unaffected. One unaffected embryo was transferred, with one healthy baby born at 38 gestational weeks., Conclusions: Targeted, capture-based next-generation sequencing for identification of informative markers together with Sanger sequencing is an easy and efficient method for the PGD of monogenic diseases such as MEN2.

The mechanism of the reactions of ClF 3 O and n -decane had two stages. The first stage was the initial reaction between ClF 3 O and n -decane. The initial reactions were investigated using a density functional theory (DFT) method. The results showed that the critical part of the mechanism of the initial reaction was the roaming of the HF intermediate. A H atom on n -decane was abstracted by a F atom on ClF 3 O to produce HF. The formed HF roamed around and then broke to give ClFO, fluorinated decane and a new HF molecule. The initial reactions were considered to be barrier-less reactions and extremely exothermic. The average released energy of the initial reactions was 412.9 kJ mol -1 , which was great enough to cause thermal decomposition of n -decane. The second stage included the reaction between ClFO and n -decane and the thermal decomposition of n -decane. The secondary reactions involving ClFO were also studied using a DFT method. ClFO was less reactive than ClF 3 O. The average energy barrier of the reactions of ClFO and n -decane was 116.3 kJ mol -1 and the average released energy was 266.5 kJ mol -1 . Thermal decomposition of n -decane was evidenced by the emission spectra of the characteristic radical intermediates CH and C 2 , which were observed using an intensified charge-coupled device (ICCD) system. The main gaseous products of the thermal decomposition of n -decane, as identified using gas chromatography, were hydrogen, ethylene and acetylene. The experimental results showed that the thermal decomposition of n -decane was an important secondary reaction following the initial reactions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Chromosomal abnormalities such as aneuploidy have been shown to be responsible for causing spontaneous abortion. Genetic evaluation of abortions is currently underperformed. Screening for aneuploidy in the products of conception can help determine the etiology. We designed a high-throughput ligation-dependent probe amplification (HLPA) assay to examine aneuploidy of 24 chromosomes in miscarriage tissues and aimed to validate the performance of this technique., Methods: We carried out aneuploidy screening in 98 fetal tissue samples collected from female subjects with singleton pregnancies who experienced spontaneous abortion. The mean maternal age was 31.6 years (range: 24-43), and the mean gestational age was 10.2 weeks (range: 4.6-14.1). HLPA was performed in parallel with array comparative genomic hybridization, which is the gold standard for aneuploidy detection in clinical practices. The results from the two platforms were compared., Results: Forty-nine out of ninety-eight samples were found to be aneuploid. HLPA showed concordance with array comparative genomic hybridization in diagnosing aneuploidy., Conclusion: High-throughput ligation-dependent probe amplification is a rapid and accurate method for aneuploidy detection. It can be used as a cost-effective screening procedure in clinical spontaneous abortions. © 2016 John Wiley & Sons, Ltd., (© 2016 John Wiley & Sons, Ltd.)

Colorectal cancer (CRC) is one of most prevalent malignant diseases worldwide. Metastasis and chemo-resistance are the two prominent death-related factors of CRCs. Thus, it is urgent to understand the mechanism responsible for the chemo-resistant properties of CRC and develop new therapeutic methods. Here, we found that the expression of miR-659-3p was significantly reduced in cisplatin (CDDP)-resistant HT29 and LOVO colorectal cancer cells and in CDDP-resistant clinical colorectal cancer samples compared with respective CDDP-sensitive counterparts. Sphingosine kinase 1 (SPHK1) is a direct target of miR-659-3p in colorectal cancer cells, and it is negatively regulated by miR-659-3p. We found that anti-miR-659-3p could increase the IC50 of CDDP in parental HT29 and LOVO colorectal cancer cells; additionally, miR-659-3p mimics decreased the IC50 of CDDP in HT29/CDDP and LOVO/CDDP colorectal cancer cells. Furthermore, we showed that the miR-659-3p/SPHK1 pathway was involved in the regulation of chemotherapy responses of colorectal cancer cells in vivo. In all, our findings suggest a new mechanism involved in the regulation of the chemotherapy response of CRC and might provide new targets for CRC prevention and treatment.

There are widespread concerns about urban sprawl in China. In response, modeling and assessing urban expansion and subsequent land use and land cover (LULC) changes have become important approaches to support decisions about appropriate development and land resource use. Guangzhou, a major metropolitan city in South China, has experienced rapid urbanization and great economic growth in the past few decades. This study applied a series of Landsat images to assess the urban expansion and subsequent LULC changes over 35 years, from 1979 to 2013. From start to end, urban expansion increased by 1512.24 km(2) with an annual growth rate of 11.25 %. There were four stages of urban growth: low rates from 1979 to 1990, increased rates from 1990 to 2001, high rates from 2001 to 2009, and steady increased rates from 2009 to 2013. There were also three different urban growth types in these different stages: edge-expansion growth, infilling growth, and spontaneous growth. Other land cover, such as cropland, forest, and mosaics of cropland and natural vegetation, were severely impacted as a result. To analyze these changes, we used landscape metrics to characterize the changes in the spatial patterns across the Guangzhou landscape and the impacts of urban growth on other types of land cover. The significant changes in LULC and urban expansion were highly correlated with economic development, population growth, technical progress, policy elements, and other similar indexes.

Unlabelled: Fat hypertrophy, intravascular coagulation, and fat emboli are important risk factors of steroid-induced ischemic bone necrosis (SI-IBN) which may develop during the initial one year after commencing the use of steroids. This pathology is best studied by MRI, particularly for its staging. The cautious strategies such as low dose, oral route, short duration of steroid usage, use of steroid sparing agent, and alcohol avoidance should be followed as a traditional therapy. The objective of this review article was to recognize and evaluate various Treatment strategies for steroid-induced ischemic bone necrosis of femoral head., Literature Search: Various electronic databases including PubMed, Google and Cochrane library were comprehensively searched for articles on steroid-induced ischemic bone necrosis of femoral head and its treatment strategies. Ninety four articles were reviewed, examined and importantly appraised and the most appropriate 32 papers were used to write this review article., Conclusion: Bisphosphonates, alendronate, and hyperbaric oxygen (HBO) treatments have been reported to be effective against IBN. To recommend the regular use of bisphosphonate in IBN patients, more evidences with a larger number of patients are required to verify its therapeutic effectiveness. Core decompression, osteotomy, bone graft and tantalum rod are the surgical approaches for the management of IBN. Advance form of IBN (bone tissue collapse) is advised to be treated with arthroplasty which should be durable, particularly in young patients.

Background: Anterior cruciate ligament reconstruction (ACLR) has developed dramatically in the last century. Now, ACLR has become a reliable and productive procedure. Patients feel satisfied in >90% cases. The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin (ACBCP) used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro., Methods: The specimens were provided by the bone banks of the First Affiliated Hospital of People's Liberation Army of General Hospital from September 2011 to June 2012. Fresh deep frozen human allogenetic cortical bone was machined into cross-pins which is 4.0 mm in diameter and 75.0 mm in length. Biomechanical parameters compared with Rigidfix were collected while cross-pins were tested in double-shear test. The load-to-failure test and cycling test were carried out in a goat model to reconstruct anterior cruciate ligament with Achilles tendon autograft on the femoral side fixed by human 4.0 mm ACBCP and 3.3 mm Rigidfix served as control. Maximum failure load, yield load, and stiffness of fixation in single load-to-failure test were compared between the two groups. Cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 were also compared in between., Results: In double-shear test both maximum failed load and yield load of 4.0 mm human ACBCP were (1 236.998±201.940) N. Maximum failed load and yield load of Rigidfix were (807.929±110.511) N and (592.483±58.821) N. The differences of maximum failed load and yield load were significant between ACBCP and Rigidfix, P < 0.05. The shear strength of ACBCP and Rigidfix were (49.243±8.039) MPa and (34.637±3.439) MPa, respectively, P < 0.05. In the load-to-failure test ex vivo, yield load and maximum failed load of ACBCP fixation complexity ((867.104±132.856)N, (1 032.243±196.281) N) were higher than those of Rigidfix ((640.935±42.836) N, (800.568±64.890) N, P < 0.05). However, stiffness did not differ significantly between ACBCP group ((247.116±31.897)N/mm) and Rigidfix group ((220.413±51.332) N/mm, P > 0.05). In the cycling test, the cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 did not differ significantly between the ACBCP group and Rigidfix group, P > 0.05., Conclusions: Allogenetic cortical bone cross-pin possesses satisfactory biomechanical profile which is safe for ACLR and suitable for an aggressive rehabilitation program. Animal and clinical tests should be recommended before clinical use to secure the ACBCP could successfully substituted by host new bone in vivo.

Background: The time until weight-bearing after arthroscopic microfracture when treating osteochondral lesions of the talus (OLT) is very important to the clinical outcomes of the operation. However, there have been no consistent opinions regarding the optimal time to start weight-bearing postoperatively. Many opinions advocate that weight-bearing should begin not earlier than the sixth or eighth week postoperatively, whereas others point out that earlier weight-bearing could also obtain satisfactory outcomes. The purpose of our study was to evaluate the clinical outcomes of early weight-bearing after arthroscopic microfracture during the treatment of OLT., Methods: Fifty-eight ankles in 58 patients with a single OLT <2 cm(2) were retrospectively studied. All lesions were treated with arthroscopic debridement and microfracture under local anesthesia. After the operation, the patients were allowed to bear full weight under the protection of figure-8-shaped splints. The visual analog scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle--hindfoot scale were evaluated preoperatively and at six postoperative timepoints (1st day, 1st month, 3rd month, 6th month, 12th month, and 24th month). Patients were followed up for 24-52 months (mean (34.97 ± 7.33) months)., Results: All 58 patients achieved excellent recovery with significant relief of their symptoms. The VAS score decreased from 7.31 ± 1.0 preoperatively to 0.95 ± 0.76 at the 24th month follow-up (P = 0.000), whereas the AOFAS score improved from 53.53 ± 8.57 preoperatively to 87.62 ± 5.42 at the 24th month follow-up (P = 0.000)., Conclusion: The successful clinical outcomes of this study demonstrated that early weight-bearing after the treatment of OLT with arthroscopic microfracture can be allowed.

There is no effective treatment for chronic rejection (CR) that largely limits long-term survival of kidney transplants. Transforming growth factor (TGF)-β is a fibrogenic factor for tissue fibrosis. This study was to test the efficacy of an anti-TGF-β antibody in preventing the CR of renal allografts in a preclinical model. Male Lewis rats (RT1¹) were orthotopically transplanted with donor kidneys from male Fischer 344 (RT11v1) rats and were treated with either anti-TGF-β or a control antibody. The CR of renal allografts was assessed by semiquantitative histological analyses, and intragraft cytokines and fibrosis-related genes ware examined by PCR arrays. Compared with the control antibody, anti-TGF-β antibody treatment significantly reduced recipients' proteinuria (P = 0.0002), and CR in renal transplants, which was indicated by the fewer injured renal tubules, glomeruli, and interlobular arterioles or arteries, and by less mononuclear cell infiltration and interstitial fibrosis in the anti-TGF-β antibody-treated group (P < 0.05), but not significantly attenuate the ratios of different infiltrating leukocytes. These pathological changes were associated with downregulation of TGF-β1, TGF-β2, and proinflammatory cytokines, or with upregulation of anti-fibrotic HGF, BMP5, and BMP7. The therapeutic effect of the anti-TGF-β antibody was further confirmed by its prevention of graft dysfunction, indicated by lower levels of serum creatinine and blood urea nitrogen or higher creatinine clearance in anti-TGF-β antibody-treated recipients compared with those in control recipients (P < 0.05). In conclusion, the anti-TGF-β antibody (1D11) treatment significantly reduces CR of renal allografts in rats, suggesting the therapeutic potential of this antibody therapy for treating CR of kidney transplants in patients.

The multilineage commitment of mesenchymal stem cells (MSCs) is controlled via unknown mechanisms. In this study, we investigated the regulation of the differentiation of MSCs into chondrocytes via the Wnt signaling pathway. Overexpression of WNT3A in MSCs activated both the canonical and non-canonical Wnt pathways, which were responsible for different WNT3A-induced outcomes. WNT3A promoted MSC proliferation via the ß-catenin-mediated canonical Wnt pathway, and inhibited chondrogenesis of MSCs via the calcium/calmodulin-dependent kinase II (CaMKII)-mediated non-canonical Wnt pathway. Interestingly, blockade of the canonical Wnt pathway by Dickkopf-related protein 1 exerted a synergistic effect on the inhibition of chondrogenesis of MSCs, while blockade of the non-canonical Wnt pathway by KN93 also exerted a synergistic effect on MSCs proliferation. These results suggest that the WNT3A-activated canonical and non-canonical pathways counteract each other in the setting of MSCs. This study provides evidence for the delicate regulation of the Wnt signaling cascade during chondrogenesis of MSCs, and suggests that genetic manipulation of the Wnt pathway may offer a powerful vehicle for modulating MSC differentiation in stem-cell-based cartilage repair.

Both humoral and cellular immune responses are involved in renal allograft rejection. Interleukin (IL)-6 is a regulatory cytokine for both B and Foxp3 (forkhead box P3)-expressing regulatory T (Treg) cells. This study was designed to investigate the impact of donor IL-6 production on renal allograft survival. Donor kidneys from IL-6 knockout (KO) vs. wild-type (WT) C57BL/6 mice (H-2(b)) were orthotopically transplanted to nephrotomized BALB/c mice (H-2(d)). Alloantibodies and Treg cells were examined by fluorescence-activated cell sorting analysis. Graft survival was determined by the time to graft failure. Here, we showed that a deficiency in IL-6 expression in donor kidneys significantly prolonged renal allograft survival compared with WT controls. IL-6 protein was upregulated in renal tubules and endothelium of renal allografts following rejection, which correlated with an increase in serum IL-6 compared with that in those receiving KO grafts or naive controls. The absence of graft-producing IL-6 or lower levels of serum IL-6 in the recipients receiving IL-6 KO allografts was associated with decreased circulating anti-graft alloantibodies and increased the percentage of intragraft CD4(+)CD25(+)Foxp3(+) Treg cells compared with those with WT allografts. In conclusion, the lack of graft-producing IL-6 significantly prolongs renal allograft survival, which is associated with reduced alloantibody production and/or increased intragraft Treg cell population, implying that targeting donor IL-6 may effectively prevent both humoral and cellular rejection of kidney transplants.