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Background: Malalignment is a common event during the intramedullary nailing (IMN) of distal tibia fractures (DTFs). Although it is reported that the semi-extended IMN techniques such as suprapatellar (SP) and parapatellar (PP) approaches may be superior in preventing malalignment, the application of these techniques is concerning owing to the intra-articular involvement. We thus developed an extra-articular semi-extended infrapatellar (SEIP) approach which utilizes the infrapatellar (IP) space while maintaining the knee in a semi-extended position. However, there are no studies on the safety and efficacy of SEIP in treating DTFs. Therefore, in this study, the SEIP technique was examined, particularly in terms of the potential alignment improvement of DTFs, and this technique was compared with the traditional hyperflexed infrapatellar (HFIP) procedure., Materials and Methods: This randomized clinical trial (RCT) compared IMN malalignment while correcting extraarticular and nondisplaced intra-articular DTFs between April 2018 and June 2021 using the HFIP and SEIP techniques at a level I trauma center in China. The study participants were clinically and radiographically examined for at least 12 months of follow-ups. Intraoperative fluoroscopy time, operation time, blood loss, hospitalization duration, functional ankle score, and complications were assessed as well., Results: Among the 88 recruited participants, 45 (51%) underwent traditional HFIP IMN and 43 (49%) underwent SEIP IMN. Malalignment occurred in 9 patients (20.0%) from the HFIP cohort and in 2 patients (4.7%) from the SEIP cohort (P value = 0.030). In addition, the SEIP IMN technique significantly reduced the intraoperative fluoroscopy time, operation time, and improved the postoperative ankle function compared to the HFIP IMN technique. However, the intraoperative blood loss, hospitalization duration, infection, delay union, and nonunion remained the same between the two cohorts., Conclusions: In summary, we demonstrated that the SEIP IMN provides markedly enhanced alignment of extraarticular and nondisplaced intra-articular DTFs compared to the traditional HFIP IMN procedure. The described technique represents an effective option for IMN of DTFs., Level of Evidence: Level 2. Trial registration The Chinese Clinical Trial Registry, ChiCTR2100043673. Registered 26 February 2021, retrospectively registered, http://www.chictr.org.cn/showprojen.aspx?proj=122263., (© 2022. The Author(s).)

How to accurately detect and efficiently sweep Cr(VI) from contaminated water has come into focus. Zirconium-based metal-organic frameworks (MOFs) play vital roles in water environmental chemistry due to excellent hydrolysis-resistant stability. However, as photochemical probes and photocatalysts, poor performances in detection sensitivity, selectivity, and photosensitiveness limit sole Zr-MOFs' applications. So, it is urgent to quest valid strategies to break through the dilemmas. Embedding luminous dyes into MOFs has been considered one of the most feasible avenues. Herein, a dual-emissive RhB@Zr-MOF with orange-yellow fluorescence has been assembled by in situ-encapsulating rhodamine B (RhB) into a zirconium-biquinoline-based MOF. Actually, within RhB@Zr-MOF, the aggregation fluorescence quenching (ACQ) effect of RhB molecules was effectively avoided. Notably, RhB@Zr-MOF exhibits a rapid fluorescence quenching response toward Cr(VI) ions with high selectivity, sensitivity, and anti-interference abilities. More interestingly, unlike the most widely reported fluorescence resonance energy transfer (FRET) between MOFs and encapsulated guest modules, photoinduced electron transfer from RhB to Zr-MOF has been confirmed by modeling the ground state and excited states of RhB@Zr-MOF using density functional theory (DFT) and time-dependent DFT (TD-DFT). The effective electron transfer makes RhB@Zr-MOF more sensitive in probing Cr 2 O 7 2- and CrO 4 2- ions with ultralow detection limit (DL) values of 6.27 and 5.26 ppb, respectively. Prominently, the detection sensitivity based on DL values has been increased about 6 and 9 times, respectively, compared with pristine Zr-MOF. Moreover, rather negative CB and positive VB potentials make RhB@Zr-MOF have excellent photochemical scavenging ability toward Cr(VI) and MO.

Thalictrum is a phylogenetically and economically important genus in the family Ranunculaceae, but is also regarded as one of the most challengingly difficult in plants for resolving the taxonomical and phylogenetical relationships of constituent taxa within this genus. Here, we sequenced the complete plastid genomes of two Thalictrum species using Illumina sequencing technology via de novo assembly. The two Thalictrum plastomes exhibited circular and typical quadripartite structure that was rather conserved in overall structure and the synteny of gene order. By updating the previously reported plastome annotation of other nine Thalictrum species, we found that the expansion or contraction of the inverted repeat region affect the boundary of the single-copy regions in Thalictrum plastome. We identified eight highly variable noncoding regions- infA-rps8 , ccsA-ndhD , trnS UGA -psbZ , trnH GUG -psbA , rpl16-rps3 , ndhG-ndhI , ndhD-psaC , and ndhJ-ndhK -that can be further used for molecular identification, phylogenetic, and phylogeographic in different species. Selective pressure and codon usage bias of all the plastid coding genes were also analyzed for the 11 species. Phylogenetic relationships showed Thalictrum is monophyly and divided into two major clades based on 11 Thalictrum plastomes. The availability of these plastomes offers valuable genetic information for accurate identification of species and taxonomy, phylogenetic resolution, and evolutionary studies of Thalictrum , and should assist with exploration and utilization of Thalictrum plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiang, Mao, Peng, Erst, Yang, He and Wu.)

Chloroplasts are critical to plant survival and adaptive evolution. The comparison of chloroplast genomes could provide insight into the adaptive evolution of closely related species. To identify potential adaptive evolution in the chloroplast genomes of four montane Zingiberaceae taxa ( Cautleya , Roscoea , Rhynchanthus , and Pommereschea ) that inhabit distinct habitats in the mountains of Yunnan, China, the nucleotide sequences of 13 complete chloroplast genomes, including five newly sequenced species, were characterized and compared. The five newly sequenced chloroplast genomes (162,878-163,831 bp) possessed typical quadripartite structures, which included a large single copy (LSC) region, a small single copy (SSC) region, and a pair of inverted repeat regions (IRa and IRb), and even though the structure was highly conserved among the 13 taxa, one of the rps19 genes was absent in Cautleya , possibly due to expansion of the LSC region. Positive selection of rpoA and ycf2 suggests that these montane species have experienced adaptive evolution to habitats with different sunlight intensities and that adaptation related to the chloroplast genome has played an important role in the evolution of Zingiberaceae taxa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Fu, Wu, Li, Zhao and Li.)

Objective: To investigate the association between magnetic resonance imaging (MRI) classification and symptom relief after uterine artery embolization (UAE) in patients with adenomyosis., Methods: Totally, 73 patients with symptomatic adenomyosis who underwent UAE were retrospectively analyzed. Preoperative MRI classification was defined as: type I, high signal on both T2-weighted images (T2WI) and T1-weighted images (T1WI); type III, high signal only on T2WI, and type II, high signal on neither T1WI nor T2WI. Dysmenorrhea was measured with the visual-analog scales and the degree of menorrhagia was measured according to the number of sanitary pads used in one menstrual cycle. Dysmenorrhea and menorrhagia were measured before UAE and 12 months after UAE., Results: The number of the type I, II, III cases was 23, 37, and 13, respectively. The baseline characteristics of the three groups exhibited no significant difference. The alleviation rates of dysmenorrhea among type I, II, III cases were 73.9%, 89.2%, and 84.6%, respectively (P=0.455). The alleviation rates of menorrhagia for type I, II, III were 69.6%, 78.4%, and 92.3%, respectively (P=0.714)., Conclusion: Pre-procedure MRI classification and symptom relief after UAE exhibited no significant association. UAE has a favorable mid-term control on dysmenorrhea and menorrhagia among patients with adenomyosis. Preoperative MRI classification might not indicate symptom relief. More research is needed before changing clinical practice., (© 2021. Huazhong University of Science and Technology.)

Background: Since December 2019, there have been many new cases of coronavirus pneumonia in Wuhan, Hubei Province, which has gradually spread throughout the country., Aim: To explore our hospital's innovative management system to ensure the efficient operation of fever clinics during the epidemic, since controlling the spread of disease is an important way to prevent and control the epidemic., Methods: In total, 200 outpatients with fever at our hospital between November 2019 and July 2020 were selected and allocated into two groups., Results: The fever clinic in our hospital operated smoothly, and infection with the novel coronavirus disease (COVID-19) has not been reported in our hospital. Additionally, we did not have any cases of missed diagnosis. The awareness regarding COVID-19 infection sources, transmission routes, early symptoms, and preventive measures was significantly higher in our fever clinic than in those of the pre-management group., Conclusion: "An integrated system, three separate responsibilities" ensured the efficient functioning of our fever outpatient clinic and early screening of COVID-19 cases, which effectively curbed the transmission of COVID-19 and hence prevented COVID-19 pneumonia epidemic in our hospital, ultimately achieving the maximum effect of epidemic prevention and control., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: Asymmetrical cortical vein sign (ACVS) shown on susceptibility-weighted imaging (SWI) can reflect regional hypoperfusion. We investigated if ACVS could predict the cerebral collateral circulation (CC) as assessed by digital subtraction angiography (DSA) in acute ischemic stroke patients with ipsilateral severe stenosis/occlusion of the anterior circulation. Methods: Clinical data and imaging data of 62 acute ischemic stroke patients with ipsilateral severe stenosis or occlusion of the anterior circulation confirmed by DSA were collected retrospectively. Participants underwent magnetic resonance imaging, including an SWI sequence. ACVS was defined as more and/or larger venous signals in the cerebral cortex of one side of SWI than that in the contralateral side. ACVS was measured using the Alberta Stroke Program Early Computed Tomography score based on SWI. The grading of the cerebral CC was judged using DSA. Results: Of the 62 patients, 30 patients (48.4%) had moderate-to-severe ACVS. According to DSA assessment, 19 patients (30.6%) had a good CC (grade 3-4), and 43 (69.4%) patients had a poor-to-moderate CC (grade 0-2). Among the 30 patients with moderate-to-severe ACVS, only three (10%) patients had a good CC, and 27 (90%) patients had a poor-to-moderate CC; among the 32 patients with none or mild ACVS, 16 (50%) of them had a good CC, and the other 50% had a moderate-to-severe CC. We constructed two logistic regression models with ACVS grading and none or mild ACVS entered into the models, respectively, together with age and large-artery occlusion. In model 1, no ACVS (compared with severe ACVS; OR = 40.329, 95%CI = 2.817-577.422, P = 0.006), mild ACVS (compared with severe ACVS; OR = 17.186, 1.735-170.224, 0.015) and large-artery occlusion (OR = 45.645, 4.603-452.592, 0.001) correlated with a good CC. In model 2, none or mild ACVS (OR = 36.848, 95%CI = 5.516-246.171, P < 0.001) was significantly associated with a good CC as judged by DSA, adjusted by age and large-artery occlusion. Conclusions: Cortical venous changes in SWI may be a useful indicator for the cerebral CC as confirmed by DSA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhan, Chen, Li, Luo, Wu, Liu, Xiao, Hu and Xie.)

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI). Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL. Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke. Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhong, Qu, Xiao, Chen, Liu, Wu, Qiu and Liang.)

Trapa bispinosa Roxb. is an annual aquatic herb with great significance of medicinal, edible and economic value. Here, we reported the complete chloroplast genome sequence of Trapa bispinosa and conducted preliminary investigation of its phylogenetic relationship with other related species. As the result showed, the whole chloroplast genome size was 155,556 bp consisting of four adjoining regions, i.e., a large/small single copy (LSC, 88,506 bp/SSC, 18,274 bp) region and two inverted repeat (IRs, 24,388 bp) regions. Among 112 identified unique genes were 78 protein coding genes, 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes. Trapa spp. were precisely clustered as a monophyly, and simultaneously, the closest relation between Trapa bispinosa and Trapa natans were strongly supported in the maximum likelihood analysis., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Lagerstroemia villosa is a kind of ornamental tree with surprising potential for applying in the landscape. We characterized the complete chloroplast genome of this scarce species and analyzed its phylogeny within Lythraceae. The result showed that the genome possessed a typical quadripartite structure, in more detail, a lager single-copy region (LSC, 88,702bp), a small single-copy region (SSC, 18,255bp), and a pair of inverted repeat regions (IRa and IRb, 26,906 bp). 78 protein-coding genes, four ribosomal RNA (rRNA) genes, and 30 transfer RNA (tRNA) genes were detected. Phylogenetic analysis based on maximum likelihood (ML) supported the closest relationship between L. villosa and Lagerstroemia limii plus Lagerstroemia subcostata ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The Japanese rhinoceros beetle Trypoxylus dichotomus is one of the largest beetle species in the world and is commonly used in traditional Chinese medicine. Ten subspecies of T. dichotomus and a related Trypoxylus species ( T. kanamorii ) have been described throughout Asia, but their taxonomic delimitations remain problematic. To clarify issues such as taxonomy, and the degree of genetic differentiation of Trypoxylus populations, we investigated the genetic structure, genetic variability, and phylogeography of 53 specimens of Trypoxylus species from 44 locations in five Asian countries (China, Japan, Korea, Thailand, and Myanmar). Using specific-locus amplified fragment sequencing (SLAF-seq) techniques, we developed 330,799 SLAFs over 114.16M reads, in turn yielding 46,939 high-resolution single nucleotide polymorphisms (SNPs) for genotyping. Phylogenetic analysis of SNPs indicated the presence of three distinct genetic groups, suggesting that the various subspecies could be treated as three groups of populations. PCA and ADMIXTURE analysis also identified three genetic clusters (North, South, West), which corresponded to their locations, suggesting that geographic factors were important in maintaining within population homogeneity and between population divergence. Analyses of SNP data confirmed the monophyly of certain subspecies on islands, while other subspecies (e.g., T. d. septentrionalis ) were found to be polyphyletic and nested in more than one lineage. AMOVA demonstrated high level of differentiation among populations/groups. Also, pairwise F ST values revealed high differentiation, particularly between South and West, as well as between North and South. Despite the differentiation, measurable gene flow was inferred between genetic clusters but at varying rates and directions. Our study demonstrated that SLAF-seq derived markers outperformed 16S and COII sequences and provided improved resolution of the genetic differentiation of rhinoceros beetle populations from a large part of the species' range., Competing Interests: All authors declare that they have no competing interests., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Introduction: Very few studies have investigated the specific relationship between neutrophil-to-lymphocyte ratio (NLR) and the short-term outcomes of patients suffering from mild acute ischemic stroke (AIS) and receiving intravenous thrombolysis (IVT). This study aimed to investigate whether a high NLR is associated with a poor short-term outcome in patients with mild AIS after IVT., Methods: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT. Mild AIS was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 7 on admission. The NLR was based on a blood test performed prior to IVT and was classified as 'high' when exceeding the 75th percentile. Follow-ups were performed at discharge and 3 months after onset. A poor outcome was defined as a modified Rankin scale (mRS) ≥3., Results: A total of 192 patients were included in this study. The median NLR was 3.0 (interquartile range [IQR]: 2.0-3.9). Fifty-one patients (26.6%) had a high NLR (≥3.9) on admission. Forty-one patients (21.4%) had a poor outcome at discharge, while 34 patients (17.7%) had a poor outcome at 3 months. Patients with a poor outcome at discharge, and at 3 months after onset, were more likely to have a high NLR at discharge (42.9% vs. 21.9%; p = .005) and at 3 months (44.1% vs. 22.8%; p = .011), compared with those with a better outcome. After adjustment for NIHSS score on admission, ipsilateral severe intracranial large artery occlusion, and atrial fibrillation, logistic regression analyses revealed that a high NLR was a significant predictor of poor outcome at discharge and at 3 months after onset., Conclusions: A high NLR on admission could be a useful marker for predicting poor short-term outcome in patients with mild AIS following IVT., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Pomegranate ( Punica granatum L.) is of great significance both as a fruit tree and an ornamental plant. Hereon, we sequenced and characterized the complete chloroplast genome of Punica granatum 'Nana' and performed phylogenetic analysis concerning related species. It turned out that the length of chloroplast genome sequence reached 158,639 bp and exhibited a four-conjoined structure, i.e., a large single copy region (LSC, 89,022 bp), a small single copy region (SSC, 18,685 bp) and twain inverted repeat regions (IRa and IRb, 25,466 bp). 112 unique genes were identified, consisting of 78 protein-coding genes, four ribosomal RNA (rRNA) genes and 30 transfer RNA (tRNA) genes. The result of phylogenetic analysis based on Neighbor-joining (NJ) method was consistent with that of Bayesian inference (BI), which strongly supported that Punica granatum 'Nana' was close to its original species Punica granatum and they together had a close relationship with Heimia myrtifolia within Lythraceae., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans., Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed., Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC&#95;004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC&#95;019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor., Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Nanotechnology has recently provided exciting platforms in the field of anticancer research with promising potentials for improving drug delivery efficacy and treatment outcomes. Nanoparticles (NPs) possess different advantages over the micro and bulk therapeutic agents, including their capability to carry high payloads of drugs, with prolonged half-life, reduced toxicity of the drugs, and increased targeting efficiency. The wide variety of nanovectors, coupled with different conjugation and encapsulation methods available for different theranostic agents provide promising opportunities to fine-tune the pharmacological properties of these agents for more effective cancer treatment methods. This review discusses applications of NPs-assisted chemotherapy in preclinical and clinical settings and recent advances in design and synthesis of different nanocarriers for chemotherapeutic agents. Moreover, physicochemical properties of different nanocarriers, their impacts on different tumor targeting strategies and effective parameters for efficient targeted drug delivery are discussed. Finally, the current approved NPs-assisted chemotherapeutic agents for clinical applications and under different phases of clinical trials are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Super enhancers (SEs) are composed of clusters of enhancers in close genomic proximity. They constitute a large family of regulatory elements that specify gene expression patterns and cell identity. SE regions consist of unusually strong enrichment of binding sites for transcriptional factors, cofactors, and enhancers associated with epigenetic modifications. SEs play important roles in regulating the aberrant gene expression in tumor cells. Via SEs, cancer cells activate the expression of various oncogenes, and promote cell proliferation, invasion and migration properties. Hence suppression of SEs activities could inhibit the growth and survival of cancer cells. In this review, we summarize the fundamental principles, functions and regulation of super enhancers and therapeutic potential in targeting SEs in cancer cells, thereby introducing and providing new conceptions for development of antineoplastic drugs.

Excessive activated T-cell proliferation was observed in vivo in one patient after an anti-CD19-chimeric antigen receptor (CAR) T-cell infusion. The patient, who had chemotherapy refractory and CD19 + diffuse large B-cell lymphoma (DLBCL), received an anti-CD19 CAR T-cell infusion following conditioning chemotherapy (fludarabine/cyclophosphamide). The lymphocyte count in the peripheral blood (PB) increased to 77 × 10 9 /L on day 13 post infusion, and the proportion of CD8 + actived T cells was 93.06% of the lymphocytes. Then, the patient suffered from fever and hypoxaemia. Significant increases in serum cytokine, lactate dehydrogenase, aspartate aminotransferase (AST), alanine transaminase (ALT), and glutamic-oxalacetic transaminase (γ-GT) levels were observed. A high-throughput sequencing analysis for T-cell receptors (TCRs) and whole-genome sequencing were used to explore the mechanisms underlying this excessive T-cell proliferation. TCR diversity was demonstrated, but no special gene mutation was found. The patient was found to be infected with the John Cunningham polyomavirus (JCV). It cannot be ruled out the bystander activation pathway induced by JCV infections related the excessive activated T-cell proliferation. Although the clinical and laboratory data do not fully explain the reason for excessive T-cell proliferation after the anti-CD19 CAR T-cell infusion, the risk of this type of toxicity should be emphasized. This study was registered at www.clinicaltrials.gov as NCT01864889.

Purpose: To investigate how necroptosis (ie, programmed necrosis) is involved in killing of non-small cell lung cancer (NSCLC) after ablative hypofractionated radiation therapy (HFRT)., Methods and Materials: Deoxyribonucleic acid damage, DNA repair, and the death form of NSCLC cells were assessed after radiation therapy. The overexpression and silencing of receptor-interacting protein kinases 3 (RIP3, a key protein involved activation of necroptosis)-stable NSCLC cell lines were successfully constructed. The form of cell death, the number and area of colonies, and the regulatory proteins of necroptosis were characterized after radiation therapy in vitro. Finally, NSCLC xenografts and patient specimens were used to examine involvement of necroptosis after ablative HFRT in vivo., Results: Radiation therapy induced expected DNA damage and repair of NSCLC cell lines, but ablative HFRT at ≥10 Gy per fraction preferentially stimulated necroptosis in NSCLC cells and xenografts with high RIP3 expression, as characterized by induction and activation of RIP3 and mixed-lineage kinase domain-like protein and release of immune-activating chemokine high-mobility group box 1. In contrast, RNA interference of RIP3 attenuated ablative HFRT-induced necroptosis and activation of its regulatory proteins. Among central early-stage NSCLC patients receiving stereotactic body radiation therapy, high expression of RIP3 was associated with improved local control and progression-free survival (all P < .05)., Conclusions: Ablative HFRT at ≥10 Gy per fraction enhances killing of NSCLC with high RIP3 expression via preferential stimulation of necroptosis. RIP3 may serve as a useful biomarker to predict favorable response to stereotactic body radiation therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Rationale: Metachronous sternal metastasis of thyroid carcinoma was a rare disease. There was no consensus in the treatment for bone metastasis after the initial thyroid carcinoma surgery., Patient Concerns: A 53-year-old female patient was hospitalized due to recurrent dull chest pains, with a history of radical right side thyroid carcinoma 4 years ago. On examination, there was an irregular mass on the lower left half of the sternum. Computerized tomography scan showed sternal bone destruction with a soft tissue mass., Diagnoses: Metachronous sternal metastasis of thyroid carcinoma., Interventions: Partial resection of the sternum and reconstruction with a titanium alloy mesh were performed., Outcomes: After a 3-year follow-up, the patient had no recurrence., Lessons: Surgical resection may be a sufficient treatment for metachronous sternal metastasis of thyroid carcinoma. Biosynthesis material mesh is preferred to be used.

The generation of layer-specific neurons and astrocytes by radial glial cells during development of the cerebral cortex follows a precise temporal sequence, which is regulated by intrinsic and extrinsic factors. The molecular mechanisms controlling the timely generation of layer-specific neurons and astrocytes remain not fully understood. In this study, we show that the adhesion molecule contactin-associated protein (Caspr), which is involved in the maintenance of the polarized domains of myelinated axons, is essential for the timing of generation of neurons and astrocytes in the developing mouse cerebral cortex. Caspr is expressed by radial glial cells, which are neural progenitor cells that generate both neurons and astrocytes. Absence of Caspr in neural progenitor cells delays the production cortical neurons and induces precocious formation of cortical astrocytes, without affecting the numbers of progenitor cells. At the molecular level, Caspr cooperates with the intracellular domain of Notch to repress transcription of the Notch effector Hes1. Suppression of Notch signaling via a Hes1 shRNA rescues the abnormal neurogenesis and astrogenesis in Caspr-deficient mice. These findings establish Caspr as a novel key regulator that controls the temporal specification of cell fate in radial glial cells of the developing cerebral cortex through Notch signaling., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background and Aim: The aim of this study is to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using CyberKnife in the treatment of patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery., Patients and Methods: Between October 1, 2006 and May 1, 2015, patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery were enrolled and treated with SBRT at our hospital. The primary end point was local control rate after SBRT. Secondary end points were overall survival, time to symptom alleviation, and toxicity, assessed using the Common Terminology Criteria for Adverse Events version 4.0., Results: Twenty-four patients with 24 lesions (17 abdominal lymph nodes and seven stumps) were treated with SBRT, of which five patients presented with abdominal lymph nodes and synchronous metastases in the liver and lung. The 6-, 12-, and 24-month actuarial local control rates were 95.2%, 83.8%, and 62.1%, respectively. For the entire cohort, the median overall survival from diagnosis and SBRT was 28.9 and 12.2 months, respectively. Symptom alleviation was observed in eleven of 14 patients (78.6%) within a median of 8 days (range, 1-14 days) after SBRT. Nine patients (37.5%) experienced Common Terminology Criteria for Adverse Events version 4.0 grade 1-2 acute toxicities; one patient experienced grade 3 acute toxicity due to thrombocytopenia., Conclusion: SBRT is a safe and effective treatment for patients with recurrent pancreatic adenocarcinoma at the abdominal lymph node or stump after surgery. Further studies are needed before SBRT can be recommended routinely.

Background and Aim: Limited-stage combined small cell esophageal carcinoma (LS-C-SCEC) is a rare, poorly understood, underdiagnosed disease, with components of both small cell esophageal cancer and non-small cell esophageal cancer. We investigated the optimal treatment strategy and prognostic factors in patients with LS-C-SCEC., Patients and Methods: LS-C-SCEC patients included in the analysis (from our hospital and the literature) were treated between January 1966 and December 2013. Patient treatment strategies included surgery (S), chemotherapy (CT), and radiation therapy (RT). The primary end point was overall survival (OS); the secondary end points included tumor complete response rates, patterns of failure, and toxicity. Kaplan-Meier curves were compared with the log-rank test. Univariate and multivariate analyses were used to determine prognosticators for OS., Results: A total of 72 patients were included in the analysis: 24 (33%) from our hospital and 48 (67%) from the literature. The median OS of all patients was 15.0 months. Patients who received CT had a significantly longer median OS than did those who did not (OS 22.8 months vs 10.0 months) (P=0.03). Patients treated with multimodality therapy (including RT+CT [18%], S+CT [40%], or S+RT+CT [17%]) vs monotherapy (typically, S [18%]) had significantly improved OS (15.5 months vs 9.3 months) (P=0.02) and complete response rates. On multivariate analysis, tumor location (upper third of the esophagus) and type of treatment (monotherapy) were the only factors predictive of poor OS., Conclusion: Multimodality therapy (including RT+CT, S+CT, or S+RT+CT) improves OS for patients with LS-C-SCEC compared with monotherapy (typically, S). Additional studies are necessary to personalize multimodal treatment approaches to individual patients.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease caused by a mutation in the adenomatous polyposis coli (APC) gene. Some studies have attempted to correlate mutations at codon 1309 with classic FAP (≥100 colorectal polyps). We report two Chinese FAP pedigrees with new frameshift mutations at codon 1309, in which affected individuals manifest phenotypic variations. Comprehensive physical examinations were performed for all living individuals and the medical data of deceased patients were collected. Screening of the APC and human mutY homolog (MUTYH) genes for germline mutations was conducted by direct polymerase chain reaction (PCR) sequencing. In two pedigrees, a heterozygous deletion in exon 16 of the APC gene was present in all FAP patients but absent in the unaffected individuals. There were no changes to the MUTYH gene. The first pedigree, with a new frameshift mutation at c.3926&#95;3930 del AAAAG (p. Glu1309Aspfs X4), exhibited obvious differences in the polyp number such that the proband manifested only three colorectal polyps, whereas another patients showed the symptoms of classic FAP. The second pedigree, also traced a new mutation at c.3922&#95;3925 del AAAG (p. Glu1309Argfs X11). Although all of the patients presented with classic polyposis, one of them exhibited a delayed onset of colorectal cancer in his 50s. Two novel mutations at codon 1309 in two Chinese families suffering from FAP could enrich the germline mutation spectrum of the APC gene. Families of individuals might manifest different phenotypes, even with an identical codon 1309 mutation, unlike in previous studies.

Effects of river (Yangtze River)-lake (Poyang Lake) relation on the distribution and potential ecological risk of Cu, Pb, Zn, Cr and Cd were investigated in surface sediment of Poyang Lake under different waterregimens. The results indicated: (1) the sediments of Poyang Lake were polluted by various concentrations of heavy metals mainly originated from particulates of Yangtze River, and Cu and Pb were the main pollution factors. The pollution level of determined heavy metals followed the order of Cu > Pb > Zn > Cr >Cd. The concentration ranges of Cu, Pb, Zn, Cr and Cd in the sediment of Poyang Lake were 13.1-108.1 mg.kg-1 , 37-119.1 mg.kg-1, 29.9-129.9 mgkg-1, 13.3-98.6 mgkg-1 and 0. 19-2.77 mg.kg-1 during the wet period, and 3.05-69.7 mg.kg-1, 27.5-105 mgkg-1, 18.8-95.4 mg.kg-1, 7.34-70 mg.kg- and 0.033-0.406 mg.kg-1 during the dry period respectively. The region with the highest heavy metal concentrations was located in water input area of the " Five River" and water output area of " Hukou" ; (2)The regions with high risk of heavy metals in sediment were mainly located in the area of the trail of "Five Rivers" during the wet period; while during the dry period, the area with high risk of heavy metals in sediment enlarged, which was not only limited in the area of the trail of "Five Rivers", but also enlarged northwards. The potential ecological risk of "Hukou" was relatively high, however, the potential ecological risk of the sediment in the whole lake during the dry period was lower than that during the wet period. (3) With the change of river-lake relation, water level rose, the maintaining time was shortened during the wet period, the dry season appeared ahead of schedule, the transformation course of Poyang Lake from "Lake morphology" to " River morphology" increased, and the typical river properties were enhanced, which resulted in the decreased potential ecological risk of heavy metals in sediment of the whole lake, however, the area of high risk-region was enlarged northwards.

Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

Background: Id3 plays a key role in the progression of breast cancer. Previously, four and a half LIM protein (FHL2) was identified as a repressor of Id family proteins by interacting with them. This study aimed to investigate the effects of FHL2 on the transcriptional regulation and oncogenic activities of Id3 in human breast cancer cells., Methods: Cell transfection was performed with SuperFect reagent. Stable transfectants that overexpressed Id3 were obtained by selection on G418. The level of Id3 protein was determined by Western blotting analysis. Dual luciferase assays were used to measure the effect of Id3 and FHL2 on E47-mediated transcriptional activity in MCF-7 human breast cancer cells. The MTT assay was used to measure cell proliferation. The transwell assay was used to measure the invasive capacity of MCF-7 cancer cells., Results: Id3 markedly repressed transcription mediated by the basic helix-loop-helix (bHLH) factor E47 in MCF-7 cells. This Id3-mediated repression was effectively antagonized by FHL2. Overexpression of Id3 markedly promoted the proliferation and invasive capacity of MCF-7 cells; however, these effects were significantly suppressed by the overexpression of FHL2., Conclusions: FHL2 can inhibit the proliferation and invasive growth of human breast cancer cells by repressing the functional activity of Id3. The functional roles of FHL2-Id3 signaling in the development of human breast cancer need further research.

Adenovirus remains a significant threat to public health. Recent studies showed that bats can harbor diverse adenoviruses. To further investigate the distribution and genetic diversity of bat adenoviruses in China, we collected throat and anal swab samples of 11 bat species from 6 provinces of China, including Beijing, Hunan, Jiangxi, Yunnan, Guizhou and Hainan. Nested PCR was used to identify potential bat adenoviruses from the samples, and positive results were cloned and sequenced for genetic diversity study. In addition, nucleotide sequence alignments based on corresponding amino acid sequence similarities were used for phylogenetic analyses. Our results showed that about 20% of bat species in China are positive to adenoviruses, and Myotis ricketti is likely to be the most important host of bat adenoviruses in all locations. Moreover, we identified two diverse sequences of bat adenoviruses from the same sample of Ia io in Guizhou province of China. In general, the average nucleotide and amino acid sequence similarities of the conserved region of DNA polymerases of bat adenoviruses are 66.6% and 74.7%, respectively. The differences between bat species and their residences environments may have driven the adaptive evolution of the viruses, leading to the genetic diversity of the bat adenoviruses.

Objective: Platelet-rich plasma (PRP) is becoming a new application in tissue engineering and a developing area for clinicians and researchers because it is a natural source of growth factors, many of which can accelerate and promote bone regeneration. However, few studies have reported the potentiality of using PRP as a scaffold in bone tissue engineering. The present study investigated the feasibility of using PRP as a scaffold to carry bone marrow stromal cells (BMSCs) to repair calvarial defects in a rabbit model., Study Design: The primary cultured BMSCs were divided into 2 groups. One group was induced with dexamethasone and the other was not induced. Full-thickness bone defects of 5-mm diameter (4 defects per calvarium) were created on the calvaria of 10 New Zealand white rabbits. PRP or whole blood was used, respectively to incorporate the induced or uninduced BMSCs. Then, the composites were activated and applied to repair the defects. The samples were harvested 8 weeks later and bone regeneration was assessed grossly and analyzed by radiographic or histologic examination., Results: Eight weeks after the implantation of the materials, substantial bone regeneration was observed at the calvarial defect restored with PRP incorporating the induced BMSCs. Less new bone formation was observed at the defect implanted with PRP incorporating the uninduced BMSCs. In contrast, no bone regeneration was detected at the defects implanted with the whole blood incorporating BMSCs, whether the BMSCs were induced or not., Conclusions: PRP can be used as a scaffold to carry in vitro expanded BMSCs to repair a rabbit's calvarial defect, but its inductive ability to BMSCs was limited., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An outbreak of hand foot and mouth disease occurred in Shang dong, China in 2009. Almost 20% of patient's swabs was positive for Coxsackie virus B5 (CVB5) identified by RT-PCR and sequencing. It was suggested that CVB5 may be another important pathogen for HFMD. Fifteen pairs of overlapping primers were designed and the genome sequence was sequenced. The genome of CVB5 was 7 399 nt in length, coding for 2 185aa. The genome displayed 80.6%-85.3% nucleotide sequence identity and 96.1%-96.9% amino acid sequence identity with another three CVB5 respectively. Phylogenetic analysis showed that different segment of genome underwent a distinct evolutionary and selective pressure. Simplot analysis displayed no evident recombination between genome of CVB5 and other HEV B viruses. The complete and characterized genome of CVB5/09 provides further insight into the genetics of CVB5 and other HEV B viruses, aiding in the surveillance and control of HFMD.

Objective: To discuss the clinical value of percutaneous transhepatic cholangial drainage (PTCD) combined with nasojejunal tube for bile reinfusion and enteral nutrition for patients with malignant obstructive jaundice., Methods: Forty patients with malignant obstructive jaundice were randomly divided into bile reinfusion group (n=20) and exclusive external drainage group (control group, n=20), and the clinical data concerning the hepatic function, visceral protein and postoperative complications of the patients were collected., Results: In both of the two groups, the levels of ALT, AST, and TB-2 reduced significantly after the operation as compared with the preperative levels (P<0.05), and no significant difference was found in the postoperative hepatic function between the two groups (P>0.05). The postoperative levels of the visceral proteins such as ALB, TRF and PRE increased significantly after the operation (P<0.05), and the changes in ALB and PRE were comparable between the two groups (P>0.05). TRF was significantly higher in bile reinfusion group than in the control group., Conclusion: PTCD combined with bile reinfusion and early enteral nutrition via the nasojejunal tube may facilitate the recovery of hepatic function and visceral proteins in patients with malignant obstructive jaundice.

Molecular cloning of major quantitative trait loci (QTLs) responsible for the reduction of rice grain shattering, a hallmark of cereal domestication, provided opportunities for in-depth investigation of domestication processes. Here, we studied nucleotide variation at the shattering loci, sh4 and qSH1, for cultivated rice, Oryza sativa ssp. indica and Oryza sativa ssp. japonica, and the wild progenitors, Oryza nivara andOryza rufipogon. The nonshattering sh4 allele was fixed in all rice cultivars, with levels of sequence polymorphism significantly reduced in both indica and japonica cultivars relative to the wild progenitors. The sh4 phylogeny together with the neutrality tests and coalescent simulations suggested that sh4 had a single origin and was fixed by artificial selection during the domestication of rice. Selection on qSH1 was not detected in indica and remained unclear in japonica. Selection on sh4 could be strong enough to have driven its fixation in a population of cultivated rice within a period of c. 100 yr. The slow fixation of the nonshattering phenotype observed at the archeological sites might be a result of relatively weak selection on mutations other than sh4 in early rice cultivation. The fixation of sh4 could have been achieved later through strong selection for the optimal phenotype.

Objective: To investigate the expression of haptoglobin in the lesions of condyloma acuminatum (CA) at the mRNA and protein level, and to explore its role in the pathogenesis of CA., Methods: The expressions of haptoglobin protein and mRNA in the skin tissues of 30 patients with CA and 20 normal controls were detected by immunohistochemistry(IHC), Western blot, and hybridization in situ., Results: The in situ hybridization study showed that haptoglobin mRNA was expressed in the epidermal cells in the lesions of CA. The distribution of haptoglobin mRNA expression in the lesions of CA was similar to that of the normal controls, and the expression of haptoglobin mRNA in CA was higher than that of the normal controls. There was a significant difference in the positive expression of haptoglobin mRNA between the CA group and the control group (P<0.05). The immunohistochemical study showed that haptoglobin protein was expressed in the whole layers of epidermal keratinocytes in the lesions of CA at a high level and stronger staining was seen in the stratum basale and stratum spinosum. Haptoglobin protein was expressed predominantly in the stratum basale in normal skin tissues, while weak staining was seen below the stratum spinosum.There was a significant difference in the mean gray value between the CA group and control group (P<0.05). Western blot showed that the haptoglobin expression in CA lesions significantly increased compared with the normal skins (P<0.05)., Conclusion: The expression of haptoglobin mRNA in the CA lesions obviously increases and the epidermal cells in the CA lesions are able to synthesize haptoglobin protein. Haptoglobin in the CA lesions may involve in the local immunity escape by preventing Langerhans cell functional maturation and inhibiting the immunocompetence of keratinocyte.

Somatic mutation in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene is associated with the sensitivity of non-smal cell lung cancer (NSCLC) to TK inhibitor Gefitinib. Mutational analysis for EGFR exons 19 and 21 was performed in 75 NSCLC and 10 breast cancer patients. All patients had not received treatment of Gefitinib. Somatic mutations in TK domain of EGFR were identified in 13 of the 75(13/75, 17.33%) patients, including 7 cases of in-frame deletion in exon 19 (7/75, 9.33%) and 6 cases of amino acid substitution (2573T>G, L858R) in exon 21 (6/75, 8%) . No other mutations were found in 10 breast cancer patients who stained positive for HER2 immunhistochemistry. Adenocarcinoma has a higher rate of mutations than several other types of NSCLC, the mutations occurring more fre-quently in female patients. EGFR mutation rate in Chinese NSCLC patients was higher than that in Caucasians. Our data indicated that Chinese adenocarcinoma patients could benefit from TK inhibitor Gefitinib.

According to the reported gene sequence of Rhizopus oryzae glucoamylases, the glucoamylase gene containing four introns was cloned from the total DNA of the natural Rhizopus arrhizu. Specific primers were designed to delete introns by overlapping PCR and a new cDNA sequence of Rhizopus arrhizu glucoamylase was obtained. The accession number in gene bank is DQ903853. This gene is successfully expressed in the Picha pastoris, producing a new protein with a high activity of glucoamylase.

Purpose: To evaluate the effect of using tissue engineered oral mucosa lamina proprias to repair buccal mucosal full-thickness defects in rats., Methods: Cultured oral mucosal fibroblasts(OMF) of Wistar rat were incorporated into chitosan-collagen to construct tissue engineered oral mucosa lamina proprias, then the OMFs were labeled with 5-BrdU. Full-thickness round mucosal defects were made with round knife (diameter of 0.8 cm) on the buccal mucosas of 21 Wistar rats(21-25 weeks old) which were divided in fibroblast-populated chitosan collagen lattices(FPCCL) group with FPCCLs transplantation and control group covered with gauges alone. All wounds were observed by macrograph or under optical microscopy and measured on 4th, 7th, 14th and/or 21st day postoperatively. The data were analyzed by SPSS11.5 software package for Student's t test., Results: There were no infection through the wound healing process. On the 7th day after grafting, the wounds of two groups were covered by yellow membrane, on the 14th, 21st day, the wounds of two groups were covered by new epidermis thoroughly, the color of new epidermis was similar to the normal one. On the 7th day, the wound diameter of control group was significantly smaller than that of FPCCL group (P<0.05). Under optical microscopy each mucosal wound in two groups was only partly keratinocyted with new granular tissue rich in inflammatory cells, fibroblasts, new vessels on the 7th day postoperatively. The wounds in two groups were keratinocyted thoroughly with rete ridges and horny layer on 14th and 21st day. OMFs with 5-BrdU appeared in the granular tissue and new lamina propria on 7th, 14th and 21st day postoperatively by immunohistochemical staining, OMFs together with granular tissue were joined in the repair of buccal mucosal defects without allergic reaction through the whole wound healing process., Conclusions: It is suggested that OMFs as the seed cells can join in the repair of buccal mucosa defects effectively; chitosan-collagen lattices have good histocompatibility; Limitation of contraction of recipient wounds will be closely related to FPCCLs; therefore, FPCCLs can repair buccal mucosal defects effectively.

Objective: To investigate the development method of hydrophobic coating porous plates for water sublimator and carry out an experimental study on hydrophobic coating porous plates., Method: Porous plates were coated with Teflon coating solution and a kind of special hydrophobic coating solution. Physical characteristic tests for hydrophobic coating porous plates were conducted. An upgrading breadboard of sublimator was redesigned. Effects of hydrophobic coating porous plates on heat rejection of water sublimator were studied., Result: Hydrophobic coating porous plate could evidently increase the water retention pressure, but also increase pressure drop of gas permeability in varying degrees. Heat rejection performance of two kinds of coating plates was different. Performance of coating plate with the special hydrophobic coating solution was better., Conclusion: Hydrophobic coating porous plate could improve performance of water sublimator by optimizing coating parameters and technics of Teflon coating solution and the special hydrophobic coating solution.