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Here, we report the complete genome sequence of Paludicola sp. strain MB14-C6, which was isolated from the lake waters of Donghu, situated at Wuhan City, Hubei Province, China. The genome of strain MB14-C6 was chosen for further species delineation and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

Here, we report the complete genome sequence of Sedimentibacter sp. strain MB35-C1, which was isolated from sewage sludge at the Wastewater Treatment Plant of Sanming Steel Co. Ltd. in Fujian, China. The resulting genome of strain MB35-C1 is a single contig of 3,621,605 bp., Competing Interests: The authors declare no conflict of interest.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4  kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15  keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1  MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Here, we report the complete genome sequence of Aminobacterium sp. strain MB27-C1, which was isolated from sewage sludge collected at the wastewater treatment plant of Sanming Steel Co. Ltd. in Fujian, China. The resulting genome of strain MB27-C1 is a single contig of 2,427,830 bp with 41.58% GC content., Competing Interests: The authors declare no conflict of interest.

We report the complete genome sequence of Anaerotignum sp. strain MB30-C6, which was isolated from the dehydrated sludge collected at the wastewater treatment plant of Sanming Steel Co. Ltd. in Fujian, China. The resulting genome of strain MB30-C6 is a single contig of 3,104,838 bp with 39.49% GC content., Competing Interests: The authors declare no conflict of interest.

To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.

Human gene editing technology is a hot spot and focus in the development of biotechnology, but it has also caused controversies over technical risks, genetic biosecurity, ethical dignity of human society and the legality of application, causing people to worry about the application of this technology. Gene editing for reproductive purposes is generally prohibited internationally, and countries have established legal regulatory systems to regulate the application of gene editing technology according to their own conditions. China shall establish a security risk access system for gene editing technology, ensure national biosecurity, establish and improve the system of ethical norms for scientific research, improve the construction of legislative standardization, and provide legal guarantees for the research and application of gene editing technology.

Here, we present the complete genome sequence of Kineothrix sp. MB12-C1 (= BCRC 81406), isolated from the feces of black soldier fly ( Hermetia illucens ) larvae. The genome of strain MB12-C1 was chosen for further species classification and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

The regeneration of periodontal, periapical, and pulpal tissues is a complex process requiring the direct involvement of cells derived from pluripotent stem cells in the periodontal ligament and dental pulp. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are spatially distinct with the potential to differentiate into similar functional and phenotypic cells. We aimed to identify the cell heterogeneity of DPSCs and PDLSCs and explore the differentiation potentials of their specialized organ-specific functions using single-cell transcriptomic analysis. Our results revealed 7 distinct clusters, with cluster 3 showing the highest potential for differentiation. Clusters 0 to 2 displayed features similar to fibroblasts. The trajectory route of the cell state transition from cluster 3 to clusters 0, 1, and 2 indicated the distinct nature of cell differentiation. PDLSCs had a higher proportion of cells (78.6%) at the G1 phase, while DPSCs had a higher proportion of cells at the S and G2/M phases (36.1%), mirroring the lower cell proliferation capacity of PDLSCs than DPSCs. Our study suggested the heterogeneity of stemness across PDLSCs and DPSCs, the similarities of these 2 stem cell compartments to be potentially integrated for regenerative strategies, and the distinct features between them potentially particularized for organ-specific functions of the dental pulp and periodontal ligament for a targeted regenerative dental tissue repair and other regeneration therapies., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Vital pulp therapy and root canal therapy (RCT) are the dominant treatment for irreversible pulpitis. While the success rate of these procedures is favorable, they have some limitations. For instance, RCT leads to removing significant dentin in the coronal third of the tooth that increases root-fracture risk, which forces tooth removal. The ideal therapeutic goal is dental pulp regeneration, which is not achievable with RCT. Specialized proresolving mediators (SPMs) are well known for inflammatory resolution. The resolution of inflammation and tissue restoration or regeneration is a dynamic and continuous process. SPMs not only have potent immune-modulating functions but also effectively promote tissue homeostasis and regeneration. Resolvins have been shown to promote dental pulp regeneration. The purpose of this study was to explore further the cellular target of Resolvin E1 (RvE1) therapy in dental pulp regeneration and the impact of RvE1 in infected pulps. We investigated the actions of RvE1 on experimentally exposed pulps with or without microbial infection in an Axin2 Cre-Dox ; Ai14 genetically defined mouse model. Our results showed RvE1 promoted Axin2-tdTomato + cell expansion and odontoblastic differentiation after direct pulp capping in the mouse, which we used to mimic reversible pulpitis cases in the clinic. In cultured mouse dental pulp stem cells (mDPSCs), RvE1 facilitated Axin2-tdTomato + cell proliferation and odontoblastic differentiation and also rescued impaired functions after lipopolysaccharide stimulation. In infected pulps exposed to the oral environment for 24 h, RvE1 suppressed inflammatory infiltration, reduced bacterial invasion in root canals, and prevented the development of apical periodontitis, while its proregenerative impact was limited. Collectively, topical treatment with RvE1 facilitated dental pulp regenerative properties by promoting Axin2-expressing cell proliferation and differentiation. It also modulated the resolution of inflammation, reduced infection severity, and prevented apical periodontitis, presenting RvE1 as a novel therapeutic for treating endodontic diseases., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.E. Van Dyke is an inventor of several granted and pending licensed and unlicensed patents (8636986, 9968577, 10434080, 2958560) awarded to the Forsyth Institute subject to consulting fees and royalty payments. All other authors declare that they have no competing interests. This work was partially fulfilled by Dr. Yu-Chiao Wu’s DMSc program requirement at Harvard School of Dental Medicine.

Here, we report the complete genome sequence of Proteiniborus sp. MB09-C3 (= BCRC 81405), isolated from the feces of black soldier fly ( Hermetia illucens ) larvae. The genome of strain MB09-C3 was selected for further species delineation and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

Introduction: Metabolic syndrome (MS) is strongly associated with cardiovascular diseases and diabetes but can be prevented with regular physical activity. This study aimed to assess the impact of a physical fitness training programme on MS among military personnel., Methods: This retrospective observational study included volunteer army soldiers who underwent annual health examinations between 2011 and 2014. In 2011, the reformed physical fitness training programme and physical fitness test were introduced to the participants. MS evaluation and physical fitness performances were evaluated before and after implementing the training programme using a mixed-effects model and generalised estimating equation, adjusted for sex, age and smoking., Results: From 2011 to 2014, 1720 soldiers underwent the annual health examination. In 2011, before the fitness programme, 246 soldiers (14.3%) had MS. After implementation, decreases in blood pressure and fasting glucose levels were observed and maintained for 3 years. Running performance was negatively correlated to triglycerides (ß=-11.37; p<0.001) and waist circumference (ß=-0.42; p<0.001) and positively correlated to high-density lipoprotein cholesterol levels (ß=2.14; p<0.001). The severity of MS was reduced following introduction of the physical fitness programme., Conclusions: MS and its components improved after introducing the reformed fitness programme, with running performance proving to be most relevant to MS. Clinicians should encourage increased physical activity to prevent MS among military personnel., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Braille system is widely used worldwide for communication by visually impaired people. However, there are still some visually impaired people who are unable to learn Braille system due to various factors, such as the age (too young or too old), brain damage, etc. A wearable and low-cost Braille recognition system may substantially help these people recognize Braille or assist them in Braille learning. In this work, we fabricated polydimethylsiloxane (PDMS)-based flexible pressure sensors to construct an electronic skin (E-skin) for the application of Braille recognition. The E-skin mimics human touch sensing function for collecting Braille information. Braille recognition is realized with a neural network based on memristors. We utilize a binary neural network algorithm with only two bias layers and three fully connected layers. Such neural network design remarkably reduces the calculation burden and, thus, the system cost. Experiments show that the system can achieve a recognition accuracy of up to 91.25%. This work demonstrates the possibility of realizing a wearable and low-cost Braille recognition system and a Braille learning-assistance system., (© 2023. The Author(s).)

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46}  cm^{2} (90% C.L.) at DM mass of 10  MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14  MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4  kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m&#95;{χ} larger than 80  MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m&#95;{χ} larger than 90  MeV/c^{2} with heavy mediators and m&#95;{χ} larger than 100  MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Objective: To investigate the clinicopathological features, surgical methods and prognosis of primary appendiceal neoplasms. Methods: A descriptive case series study was performed. Clinical data of patients diagnosed with primary appendiceal neoplasms in Peking University First Hospital from 2006 to 2017 were retrospectively analyzed. Patients who underwent surgery and were confirmed as appendiceal neoplasms by postoperative pathology were included. Cases of cecal tumor invading the appendix and other organ tumors implanting in the appendix and cases of recurrent appendix tumors were excluded Pathological classification was based on the 4th edition of the WHO classification of digestive tract tumors (2010 edition), and the efficacy of operation methods of low grade appendiceal mucinous neoplasm (LAMN) were analyzed. Results: A total of 115 patients were enrolled, including 52 males and 63 females with a median age of 59 (51, 71) years. Clinical symptoms usually manifested as dormant pain in the right lower quadrant, migrating right lower abdominal pain, fever and bloating. Twenty-four cases were accidentally discovered during surgery, and 21 cases were found by physical examination. The preoperative diagnosis rate of CT and ultrasound was 40.2% (43/107) and 25.5% (24/94) respectively. The postoperative pathological types contained 83 cases of LAMN, 12 cases of mucinous adenocarcinoma, 9 cases of appendiceal neuroendocrine neoplasms (aNEN), 2 cases of mucinous adenocarcinoma with signet ring cells, 3 cases of serrated adenoma, 2 cases of goblet cell carcinoid, 2 cases of lymphoma, 1 case of leiomyoma and 1 case of schwannomas. All the patients underwent surgical resection, including 41 cases of appendectomy, 21 cases of partial cecectomy, 48 cases of right hemicolectomy, and 5 cases of combined organ resection due to appendiceal tumor infiltration or dissemination. Eighteen cases were diagnosed with pseudomyxoma peritonei (PMP) during operation. A total of 98 patients were enrolled for follow-up. The median follow-up time was 58 (5-172) months. The 5-year disease-free survival (DFS) rate was 84.5% and 5-year overall survival (OS) was 88.2%. Multivariate analysis revealed that high-grade malignancy tumors (HR=25.881, 95% CI: 2.827-236.935, P =0.004) and PMP formation (HR=42.166, 95% CI: 3.470-512.439, P =0.003) were independent risk factors for prognosis. Patients undergoing right hemicolectomy presented longer operation time, more blood loss and higher morbidity of complication as compared to those undergoing appendectomy and partial cecectomy (all P <0.05), while no significant differences in 5-year DFS ( P =0.627) and 5-year OS ( P =0.718) were found. Conclusions: Primary appendiceal neoplasms usually have no typical features, accompanied with low preoperative diagnosis rate. The common pathological types are LAMN, mucinous adenocarcinoma and aNEN. Appendectomy or partial cecectomy for LAMN may achieve satisfactory prognosis. High-grade malignancy tumors and PMP formation are independent risk factors for prognosis.

Objective: Most patients with asymptomatic colorectal diverticulosis are easily overlooked. However, some of diverticulosis become diverticulitis, bleeding and even perforation, which cause extensive harm to patients. The purpose of this study is to analyze the incidence, clinical features, diagnosis and treatment of colorectal diverticulosis in order to improve the clinical understanding of diverticulosis and its related complications. Methods: A descriptive cohort study was carried out. Clinical data of 554 patients with colorectal diverticulosis confirmed by CT, colonoscopy, digestive tract radiography or operation in Peking University First Hospital from January 2009 to June 2019 were retrospectively analyzed. Patients with malignant tumors, autoimmune diseases, long term use of immunosuppressive drugs, chronic liver diseases and renal diseases, and mental disorders were excluded. The analysis parameters included gender, onset age, clinical symptoms, location of diverticulitis, treatment and prognosis. According to the criteria established by the World Society of Emergency Surgery (WSES), acute diverticulitis was divided into 5 stages based on the extension of the infectious process. Stage 0 was simple diverticulitis and stage 1-4 was complicated diverticulitis. Results: Among the 554 patients with colorectal diverticulosis, 358 (64.6%) were males, the median onset age was 63 years; 191 patients (34.5%) had various digestive symptoms, of whom 113 (20.4%) had chronic constipation and abdominal distension, 78 (14.1%) had chronic diarrhea and abdominal pain; the other 363 patients had no obvious abdominal symptoms. Four hundred and six patients were found by colonoscopy and 465 patients were found by CT. Twenty-five patients were diagnosed by lower gastrointestinal tract radiography and 3 were confirmed during operation. There were 339 patients with multiple diverticula (61.2%) and 215 patients with single diverticulum (38.8%). 76.5% (424/554) of diverticula were located in colon, 37.0% (205/554) in ascending colon, 21.3% (118/554) in multiple sites, and 2.2% (12/554) in rectum. The median diameter of diverticulum was 7 mm, and 78 cases (14.1%) was ≥30 mm. Forty-nine patients (8.8%) developed acute diverticulitis, including 13 patients with simple diverticulitis and 36 patients with complicated diverticulitis. Among 36 patients with complicated diverticulitis, 29 (80.6%) were males, 27 (75.0%) had recurrent abdominal pain and fever before onset; diverticula of 25 cases were located in sigmoid colon; 11 cases in ascending colon. Nine cases developed sigmoid colon perforation and 8 cases developed vesicocolonic fistula, and these 17 patients underwent surgical treatment. The other 19 cases with complicated diverticulitis developed gastrointestinal bleeding, of whom 18 cases were male, 11 cases were located in ascending colon; 13 cases were healed after conservative treatment, 4 cases received endoscopic hemostatic intervention, and 2 cases underwent surgery. Conclusions: Colorectal diverticulosis is more common in male patients, and CT and colonoscopy are main diagnostic methods. The symptoms of complicated colonic diverticulitis are related to the location of diverticulum. In addition to symptomatic treatment, surgical procedures are the most important treatments.

Background: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors., Methods: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction., Results: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS&#95;00516490, TCONS&#95;00336559, TCONS&#95;00311568, TCONS&#95;00321917, TCONS&#95;00336522, TCONS&#95;00282483, and TCONS&#95;00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers., Conclusions: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers., (© 2021. Italian Society of Endocrinology (SIE).)

Objective: The surgical indications, resection extent and management principle of lateral lymph node dissection (LLND) in lower rectal cancer have been controversial between Eastern and Western countries. This study aims to provide a theoretical basis for the rational implementation of LLND by reviewing the changes of LLND strategy over the past 30 years in a single-center, and analyzing prognostic factors for the survival outcomes of patients with lateral lymph node metastasis (LLNM). Methods: A retrospective observational study was performed. Clinical data of 289 patients with rectal cancer who received LLND at the Department of General Surgery of Peking University First Hospital from 1990 to 2019 were collected. Patients were divided into three groups based on decades. There were 89 cases in 1990-1999 group, 92 cases in the 2000-2009 group, and 108 cases in the 2010-2019 group. Data analyzed: (1) patient baseline data; (2) surgery and postoperative recovery; (3) lateral lymph node dissection; (4) postoperative survival and prognosis of patients with positive lateral lymph nodes. The surgical methods and pathological results of LLND were compared between groups, and the prognostic risk factors of patients with LLNM were analyzed. Results: A total of 289 patients underwent radical resection with LLND' accounting for 6.3% of the 4542 patients with rectal cancer during the same period in our hospital. Except decade-by-decade increase in tumors with distance from anal verge ≤ 7 cm, the proportion of ulcerated tumors, and the proportion of neoadjuvant radiochemotherapy, the differences in other baseline data were not statistically significant among 3 decade groups (all P >0.05). The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2490), χ(2)=40.159, P <0.001]. The proportion of laparoscopic surgery and unilateral LLND increased, while the mean operative time, intraoperative blood loss, surgical complications above grade III and postoperative hospital stay decreased decade by decade. These 289 patients completed a total of 483 lateral dissections, including 95 cases of the unilateral dissection and 194 cases of the bilateral dissection. The proportion of LLND in the 3 groups decreased decade by decade [9.9% (89/898) vs. 8.0% (92/1154) vs. 4.3% (108/2510), P <0.001]. The median number of dissected lymph nodes in the internal iliac artery and obturator regions increased (2 vs. 3 vs. 3, P <0.001), but those in the common iliac and external iliac regions decreased significantly (4 vs. 3 vs. 2, P =0.014). A total of 71 patients with LLNM were identified. The rate of LLNM in the 2010-2019 group was significantly higher than that in the previous two groups [37.0% (40/108) vs. 16.9% (15/89) vs. 17.4% (16/92), P =0.001]. The patients with LLNM showed a poorer overall survival (OS) and disease-free survival (DFS) compared with negative lateral lymph nodes ( P <0.001). There were statistically significant differences in 5-year OS rate (30.9% vs. 27.2% vs. 0, P =0.028) and 5-year DFS rate (28.3% vs. 16.0% vs. 0, P =0.038) among patients with only internal iliac lymph node metastasis, patients with only obturator lymph node metastasis, and patients with external iliac or common iliac lymph node metastasis. Multivariate analysis of prognostic factors showed that external iliac or common iliac lymph node metastasis was an independent risk factor for OS (HR=1.649, 95%CI: 1.087-2.501) and DFS (HR=1.714, 95%CI: 1.173-2.504) in patients with LLNM (all P <0.05) . The OS and DFS were not significant different in patients with LLNM among 3 decade groups. Conclusions: In the past decade, the proportion of LLND in rectal cancer has decreased significantly. However, LLNM rate has been significantly increased due to preoperative imaging assessments focusing on suspicious LLNM without compromising the survival. Internal iliac artery and obturator lymph nodes can be regarded as regional lymph nodes with a satisfactory prognosis after LLND. For suspected external iliac or common iliac lymph node metastasis, the significance of LLND remains to be further evaluated.

Objective: To investigate the clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma (FH-RCC)., Methods: Immunohistochemical (IHC) staining was used to detect the expression of fumarate hydratase (FH) in tumor tissues of 109 different types of renal cell carcinoma (RCC) patients aged 60 years and younger from the Department of Urology of Peking University First Hospital from January 2013 to December 2019. The clinicopathological data and prognosis of FH-RCC were collected and analyzed., Results: There were eleven patients with FH-negative expression. Seven were males and four females. The age of onset ranged 16-53 years (mean age: 36.7 years), and four female patients all had a history of uterine leiomyoma. Only one first-degree relative of one patient had renal cancer, and none of the patients had a history or family history of cutaneous leiomyomas. The diameter of the tumor was 2.1-12.0 cm (mean: 8.83 cm). Renal sinus or perirenal fat invasion was seen in nine cases, tumor thrombus in renal vein or inferior vena cava in six cases, lymph node metastasis in seven cases, adrenal gland invasion in four cases and splenic capsule invasion in one case. The cases were initially diagnosed as type Ⅱ papillary RCC (7/49, 14.3%), collecting duct carcinoma (2/9, 22.2%) and unclassified RCC (2/51, 3.9%). Tumor histopathology mostly showed a mixture of different structures, such as papillary, tubular cystic, solid, and so on. The most common histological structures were papillary (9/11, 81.8%) and tubular (8/11, 72.7%). Three cases had sarcomatoid areas. At least focal eosinophilic nucleolus (WHO/grades Ⅲ-Ⅳ) and perinuclear halo could be seen in all cases. Immunohistochemical (IHC) stains of most tumors were negative for CA9, CD10 and CK7. The results of fluorescence in situ hybridization (FISH) showed that there was no translocation or amplification of TFE3 gene in two cases with TFE3 IHC expression. All the patients were followed up for 11-82 months. Mean survival was 24 months. Five cases died of distant metastasis 9-31 months after operation (mean: 19 months), and five of the six patients alive had became metastatic., Conclusion: Morphologically, FH-RCC overlaps with many types cell RCC. A mixture of papillary and tubular cystic arrangement is the most common growth pattern of FH-RCC. At least focally large and obvious eosinophilic nucleoli are an important histological feature of this tumor. The negative expression of FH can help to confirm the diagnosis. Young female RCC patients with uterine leiomyomas should be suspected of FH-RCC. Some FH-RCC cases lack clinical evidence. The suspicion raised by pathologists based on histological characteristics is often the key step to further genetic testing and the final diagnosis of the tumor.

Aim: To compare the performance and reading time of different readers using automatic artificial intelligence (AI)-powered computer-aided detection (CAD) to detect lung nodules in different reading modes., Materials and Methods: One hundred and fifty multidetector computed tomography (CT) datasets containing 340 nodules ≤10 mm in diameter were collected retrospectively. A CAD with vessel-suppressed function was used to interpret the images. Three junior and three senior readers were assigned to read (1) CT images without CAD, (2) second-read using CAD in which CAD was applied only after initial unassisted assessment, and (3) a concurrent read with CAD in which CAD was applied at the start of assessment. Diagnostic performances and reading times were compared using analysis of variance., Results: For all readers, the mean sensitivity improved from 64% (95% confidence interval [CI]: 62%, 66%) for the without-CAD mode to 82% (95% CI: 80%, 84%) for the second-reading mode and to 80% (95% CI: 79%, 82%) for the concurrent-reading mode (p<0.001). There was no significant difference between the two modes in terms of the mean sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for both junior and senior readers and all readers (p>0.05). The reading time of all readers was significantly shorter for the concurrent-reading mode (124 ± 25 seconds) compared to without CAD (156 ± 34 seconds; p<0.001) and the second-reading mode (197 ± 46 seconds; p<0.001)., Conclusion: In CAD for lung nodules at CT, the second-reading mode and concurrent-reading mode may improve detection performance for all readers in both screening and clinical routine practice. Concurrent use of CAD is more efficient for both junior and senior readers., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the correlation between clinicopathological features and lymph node metastasis, and to evaluate the feasibility and efficacy of endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) by comparing with surgery treatment., Methods: The clinicopathological data of 320 patients with EGC who were treated in Peking University First Hospital between January 2010 and December 2017 were retrospectively reviewed, in which there were 198 cases of surgical procedure and 122 cases of ESD. Characteristics of lymph node metastasis in EGC were analyzed, and lymph node metastasis of EGC with ESD absolute and expanded indications were summarized. The long-term efficacy of ESD and surgical treatment of EGC were compared to evaluate the rationality of absolute and expanded indications of ESD., Results: Lymph node metastasis was detected in 22 (11.1%) of 198 patients. Univariate analysis showed a positive relationship between tumor size ( χ 2 =5.525, P =0.019), depth of invasion( χ 2 =8.235, P =0.004), histological type ( χ 2 =6.323, P =0.012), lymphovascular invasion ( χ 2 =12.273, P < 0.001) and lymph node metastasis in EGC. Multivariate analysis revealed that depth of invasion( Wald =7.575, P =0.006) and histological type ( Wald =6.317, P =0.012) were independent relative factors of lymph node metastasis in EGC. The lymph node metastasis rates of the patients with absolute and expanded ESD indications were both 0%. The 5-year survival rates of the patients who met ESD absolute indication receiving surgery treatment and ESD were 97.6% and 97.9% respectively, and the difference between the two groups was not statistically significant( χ 2 =0.014, P =0.907).The 5-year survival rates of the patients who met ESD expanded indication receiving surgery treatment and ESD were 96.5% and 91.7% respectively, the difference between the two groups was not statistically significant( χ 2 =1.061, P =0.303)., Conclusion: Lymph node metastasis in EGC is mainly correlated with depth of invasion and histological type. Our data indicate that ESD procedure for EGC is comparable to surgery in terms of long-term efficacy in both absolute and expanded indications. However, some studies of a large sample size are still needed for more confirmation.

The prognostic impact of circumferential resection margin (CRM) in surgically resected esophageal squamous cell carcinoma (ESCC) has been controversial. This investigation assessed the prognostic impact of CRM in surgically resected pathologic T3 ESCC patients with or without neoadjuvant chemoradiotherapy (nCRT). We reviewed consecutive p/yp T3 ESCC patients undergoing esophagectomy from two medical centers between January 2009 and December 2016. The cohort was divided into two groups: upfront esophagectomy (upfront surgery) and nCRT followed by esophagectomy (nCRT + surgery). CRM status was assessed and divided into CRM > 1 mm, 0 < CRM < 1 mm, and tumor at CRM. A total of 217 p/yp T3 ESCC patients undergoing esophagectomy (138 patients in the upfront surgery group and 79 in the nCRT + surgery group) were enrolled. In the upfront surgery group, patients with 0 < CRM < 1 mm showed equivalent overall survival to those with CRM > 1 mm (log-rank P = 0.817) and significantly outlived those with tumor at CRM (log-rank P < 0.001). However, in the nCRT + surgery group, CRM > 1 mm failed to show survival superiority to CRM between 0 and 1 mm or involved by cancer (log-rank P = 0.390). In conclusion, a negative CRM, even though being <1 mm, is adequate for pT3 ESCC patients undergoing upfront esophagectomy. In contrast, the CRM status is less prognostic in ypT3 ESCC patients undergoing nCRT followed by esophagectomy., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC). Methods: A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ(2) test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results: A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n =28), posterior pelvic exenteration ( n =32), and total pelvic exenteration ( n =51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P <0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P <0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P =0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P <0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P =0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P <0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P =0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P =0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P =0.013) were independent factors affecting the prognosis. Conclusions: The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m&#95;{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m&#95;{χ}<6  GeV/c^{2} among WIMP AM measurements to date.

We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (m&#95;{χ}) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in m&#95;{χ} are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σ&#95;{χN}^{SI} at 90% confidence level are derived as 2×10^{-32}∼7×10^{-35}  cm^{2} for TI analysis at m&#95;{χ}∼50-180  MeV/c^{2}, and 3×10^{-32}∼9×10^{-38}  cm^{2} for AM analysis at m&#95;{χ}∼75  MeV/c^{2}-3.0  GeV/c^{2}.

Objective: Papillary thyroid carcinoma (PTC) is an endocrine malignancy, the morbidity of which has kept rising in recent years. MicroRNA (miRNA/miR) is emerging as a key regulator in carcinogenesis, including PTC. The current study concentrates on the biological roles and mechanisms of miR-26a in the PTC progression., Patients and Methods: 51 pairs of PTC tissue samples and matched adjacent thyroid tissues were collected from PTC patients who received surgical excisions at The People's Hospital of Linqing between July 2015 and June 2018 with informed consent. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect expressions of miR-26a and rho-associated coiled-coil-containing protein kinase 1 (ROCK1) mRNA in PTC tissues and cells. Functional assays, including (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) MTT assays and transwell assays were performed to determine the roles of miR-26a in the PTC progression. Western blot was used to detect expression levels of the related proteins., Results: Findings demonstrated prominently down-regulated miR-26a in PTC tissues and cells. Down-regulated miR-26a indicated malignant clinicopathologic characteristics and shorter overall survival rate of PTC patients. MTT assay and transwell assay indicated that miR-26a up-regulation significantly repressed PTC cell viability, invasion, and metastasis. Western blot analysis revealed that miR-26a exerted its anti-PTC effects via phosphatidylinositol 3-kinase/protein kinase B pathway (PI3K/AKT) and epithelial-to-mesenchymal transition (EMT). ROCK1 was a target of miR-26a in PTC cells and ROCK1 was mediated by miR-26a, as a regulatory mechanism in PTC., Conclusions: Taken together, these findings demonstrated the anti-tumor functions of miR-26a in PTC, providing novel strategies for PTC diagnosis and therapy.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

Computed Tomography (CT) is a powerful method for non-destructive testing (NDT) and metrology awakes with expanding application fields. To improve the spatial resolution of high energy CT, a micro-spot gamma-ray source based on bremsstrahlung from a laser wakefield accelerator was developed. A high energy CT using the source was performed, which shows that the resolution of reconstruction can reach 100 μm at 10% contrast. Our proof-of-principle demonstration indicates that laser driven micro-spot gamma-ray sources provide a prospective way to increase the spatial resolution and toward to high energy micro CT. Due to the advantage in spatial resolution, laser based high energy CT represents a large potential for many NDT applications.

Background and Objective: The response to nonsurgical periodontal treatment varied among patients. This study assessed the potential of salivary biomarkers for predicting the sensitivity and monitoring the response to nonsurgical periodontal therapy., Material and Methods: This study recruited 34 participants with severe chronic periodontitis (the test group) and 20 participants without periodontal destruction in any teeth (the control group) from September 6, 2013 to August 25, 2017. Participants in the test group received nonsurgical periodontal therapy and were further divided into 2 subgroups of 17 low responders and 17 high responders, based on probing depth reduction. Clinical periodontal parameters were recorded, and saliva samples were harvested before and after nonsurgical periodontal therapy. Salivary biomarkers, including interleukin (IL)-1beta (IL-1β), IL-1 receptor antagonist (IL-1ra), IL-6, IL-8, platelet-derived growth factor-BB, vascular endothelial growth factor, MMP-8, MMP-9, C-reactive protein, and lactoferrin were analyzed., Results: Compared with participants in the control group, participants in the test group had significantly greater periodontal pocket depth, clinical attachment level, and salivary IL-1β and MMP-8 levels, and all of these parameters were significantly reduced after nonsurgical periodontal therapy. The pretreatment levels of IL-1β, MMP-8, and lactoferrin were significantly higher in participants of the high-responder subgroup than participants of the low-responder subgroup.Based on the analysis from a dichotomous table, MMP-8 and lactoferrin showed odds ratios of 5.76, with 71% sensitivity and 71% specificity, and statistical significance (P = .02) for discriminating between the high- and low-responder subgroups., Conclusion: Salivary IL-1β and MMP-8 might be useful for diagnosing periodontitis and monitoring the recovery of periodontitis following nonsurgical periodontal therapy. MMP-8 and lactoferrin showed potential for predicting the sensitivity to the treatment., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36}  cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m&#95;{χ}) of 5  GeV/c^{2} are achieved. The lower reach of m&#95;{χ} is extended to 2  GeV/c^{2}.

Natural deep eutectic solvents (NADESs) are efficient in extracting natural products. However, traditional organic solvents are toxic in the extraction of anthraquinones from Rheum palmatum L. To solve this problem, we applied natural deep eutectic solvent ultrasound-assisted extraction in this study for the extraction of total anthraquinones from R. palmatum L. Principal component analysis revealed that the selected NADES which consisted of lactic acid, glucose and water (LGH), was highly efficient in extracting anthraquinones from R. palmatum L. The ratio of lactic acid/glucose and the addition of water in LGH were investigated via a single-factor experiment. With a lactic acid/glucose ratio of 5 : 1 (mol/mol), and 10% of water (v/v), LGH had a high extraction yield to anthraquinones. Optimized by response surface methodology (RSM), the optimized extraction conditions of extraction time, extraction temperature and solvent-to-solid ratio of 1.5 h, 82 °C and 26 mL g -1 , respectively. Under optimum conditions, the extraction yields of aloe-emodin, rhein, emodin, chrysophanol, physcion and total anthraquinones were 2.60 ± 0.01, 5.78 ± 0.02, 2.21 ± 0.02, 5.87 ± 0.02, 8.81 ± 0.01 and 25.27 ± 0.07 mg g -1 , respectively. The enrichment and separation of five anthraquinones in LGH extraction solution were efficiently achieved using DM130 macroporous resin, with purities of 90.98%, 96.67%, 92.37%, 95.80% and 91.61% as indicated by HPLC, and recovery yields of 84.08%, 79.51%, 84.96%, 81.83% and 78.35%, respectively. LGH was environmentally friendly and highly efficient in extracting anthraquinones from R. palmatum L., and NADESs showed potential for the extraction of effective components from natural products., Competing Interests: Authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

We used ethylenediaminetetraacetic acid dianhydride (EDTAD) to modify oxalate decarboxylase (OXDC) to improve its adsorption on calcium oxalate stones. The modified sites were identified by Ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and the adsorption mechanism of the EDTAD-modified OXDC on calcium oxalate (CaOx) was investigated. We investigated adsorption time, initial enzyme concentration, temperature and solution pH on the adsorption process. Data were analyzed using kinetics, thermodynamics and isotherm adsorption models. UPLC-MS showed that EDTAD was attached to OXDC covalently and suggested that the chemical modification occurred at both the free amino of the side chain and the α-NH 2 of the peptide. The adsorption capacity of the EDTAD-OXDC on calcium oxalate was 53.37% greater than that of OXDC at the initial enzyme concentration of 5 mg/ml, pH = 7.0, at 37° C. The modified enzyme (EDTAD-OXDC) demonstrated improved oxalate degradation activity at pH 4.5-6.0. Kinetic data fitting analysis suggested a pseudo second order kinetic model. Estimates of the thermodynamic parameters including ΔG 0 , ΔH 0 and ΔS 0 of the adsorption process showed it to be feasible, spontaneous and endothermic. Isotherm data fitting analysis indicated that the adsorption process is reduced to monolayer adsorption at a low enzyme concentration and to multilayer adsorption at a high enzyme concentration. It may be possible to apply OXDC to degradation of calcium oxalate stones.

Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load. The Shapiro-Wilk test and the Levene test were used to evaluate data normality and homogeneity of variances, and the t-test or the non-parametric Mann-Whitney U test was selected based on data type and was used for the comparison of means between groups. The Hardy-Weinberg equilibrium was used to determine the genotype of SNPs, and the dominant model, recessive model, and additive model were used for analysis. Results: Mothers with an AA/AG genotype of rs3130542 in the HLA-C gene had a significantly higher probability of HBV DNA load ≥10(3) IU/ml at the time of delivery ( P < 0.05) and a significantly higher risk of failure in the prevention of mother-to-child transmission, no matter whether they started to take telbivudine at week 24 or 28 of pregnancy. The association between the genotype of rs4821116 in the UBE2L3 gene and the reduction in viral load in pregnant women needed to be confirmed by studies with a larger sample size. Conclusion: Pregnant women with a high viral load and an AA/AG genotype of rs3130542 in the HLA-C gene tend to have poor response to antiviral therapy during pregnancy, and early antiviral intervention is recommended for such patients.

Electrons can be efficiently injected into a plasma wave by colliding two counterpropagating laser pulses in a laser wakefield acceleration. However, the generation of a high-quality electron beam with a large charge is difficult in the traditional on-axis colliding scheme due to the growth of the electron beam duration coming from the increase of the beam charge. To solve this problem, we propose an off-axis colliding scheme, in which the collision point is away from the axis of the driver pulse. We show that the electrons injected from the off-axis region are highly concentered on the tail of the bubble even for a large trapped charge, thus feeling almost the same accelerating field. As a result, quasimonoenergetic electron beams with a large charge can be produced. The validity of this scheme is confirmed by both the particle-in-cell simulations and the Hamiltonian model. Furthermore, it is shown that a Laguerre-Gauss (LG) laser can be adopted as the injection pulse to realize the off-axis colliding injection in three dimensions symmetrically, which may be useful in simplifying the technical layout of the real experiment setup.

Background: Patterns of recurrence after surgery with postoperative chemoradiotherapy (S-CCRT) or surgery alone in patients with oesophageal squamous cell carcinoma (SCC) may differ. This might influence the nature and timing of subsequent management strategies., Methods: Patients with SCC who had undergone R0 resection were included. Propensity score matching was used to select matched groups. Survival and recurrence were compared by Kaplan-Meier analysis. Univariable and multivariable Cox regression analyses were used to identify prognostic factors for overall and disease-free survival., Results: A total of 1390 patients were included, of whom 1000 had surgery alone and 390 underwent S-CCRT. Propensity score matching yielded 213 well balanced pairs. The 3-year overall survival rate and median survival time in the S-CCRT group were 0·50 and 36·5 (95 per cent c.i. 25·1 to 52·6) months respectively, compared with 0·38 and 22·8 (18·2 to 29·0) months in the surgery-alone group (P = 0·006). The 3-year disease-free survival rate and median disease-free survival time in the S-CCRT group were 0·46 and 30·6 (22·2 to 39·3) months respectively, compared with 0·36 and 17·6 (11·3 to 23·9) months in the surgery-alone group (P = 0·006). The 2-year freedom from locoregional recurrence rate was 0·87 and 0·77 in the S-CCRT and surgery-alone groups respectively (P = 0·003). In multivariable analysis, independent prognostic factors for disease-free survival included age over 56 years, pT3-4 category, pN category, poor differentiation, tumour length exceeding 4·0 cm, and receiving postoperative chemoradiotherapy (hazard ratio 0·62, 95 per cent c.i. 0·47 to 0·81; P < 0·001)., Conclusion: Oesophagectomy with postoperative chemoradiotherapy was associated with longer survival and lower recurrence rates, especially at a locoregional level, compared with surgery alone., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective: To investigate expression changes and role of Gα11 protein in the processes of muscularization of non-muscular pulmonary arterioles and effect of sildenafil intervention in rats with pulmonary arterial hypertension (PAH)., Methods: Thirty SD rats were randomly divided into three groups, including normal control group, monocrotaline (MCT) group and sildenafil group; PAH model was prepared with 50 mg/kg MCT treatment for 4 weeks in the MCT group, and these rats were treated by 25 mg/kg sildenafil for 2 weeks after PAH formation in the sildenafil group, and the normal control group were treated with the equal amounts of physiological saline instead of monocrotaline; pulmonary artery pressure was measured with jugular vein catheterization; hematoxylin and eosin (HE) staining method was used to detect the pulmonary arteriolar morphology and vascular tissue parameters; expression of the target Gα11 protein, vascular smooth muscle marker osteopontin (OPN) and proliferation marker proliferating cell nuclear antigen (PCNA) was detected by Western blot., Results: Pulmonary artery mean pressure (mPAP), non-muscular pulmonary arterioles wall thickness index (TI) and area index (AI) of the MCT group were higher than those of the normal control group[(27.43±3.97) vs (11.93±1.52) mmHg (1 mmHg=0.133 kPa), 0.49±0.07 vs 0.31±0.09 and 0.74±0.05 vs 0.45±0.10](all P<0.05), and meanwhile the expression levels of Gα11 and the related proteins including OPN and PCNA were significantly enhanced. mPAP, TI and AI[(18.59±1.44) mmHg, 0.39±0.09 and 0.56±0.04]of the sildenafil group were all lower than those of the MCT group (all P<0.05), and furthermore, expressions of Gα11, OPN and PCNA also reduced in line with these changes., Conclusion: Gα11 protein plays a role in the development of PAH and pulmonary non-muscular arteriole muscularization, and sildenafil effectively suppresses PAH and pulmonary vascular remodeling by inhibiting Gα11 expression.

This study confirmed that the infection of nervous necrosis virus (NNV), belonging to the betanodavirus, can induce the expression of endogenous Mx in grouper fin-3 (GF-3), grouper brain (cGB), and barramundi brain (cBB) cells, but not in grouper fin-1 (GF-1) cells. In a co-sedimentation assay, RdRp appeared in the mitochondrial pellet of GF-1 cells without endogenous Mx expression. However, in GF-3, cGB, and cBB cells, RdRp was detected in the nuclear pellet accompanied by endogenous Mx. By immunostaining, RdRp was found to colocalize with not only endogenous Mx but also lysosomes and monodansylcadaverine (MDC)-labeled autophagic vacuoles. In GF-1 cells, the RdRp level continuously increased during 24-72 h post infection (hpi). When endogenous Mx expressed during 24-72 hpi in virus-infected GF-3, cGB, and cBB cells, the RdRp level peaked at 24 hpi but decreased at 48-72 hpi. The degradation of RdRp could be suppressed by treatment with 3-methyladenine (3MA), NH4Cl, and Mx-specific siRNA respectively. After poly I:C transfection, the endogenous Mx level peaked at 3 days post transfection (dpt) and then spontaneously decreased at 5-7 dpt. The poly I:C-indued Mx also colocalized with MDC-labeled autophagic vacuoles at 3 dpt, and its degradation could be inhibited by 3MA or NH4Cl treatments. Therefore, the anti-NNV mechanism of endogenous grouper and barramundi Mx is suggested to sequester RdRp for degradation through autophagy and lysosomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In the tumor microenvironment, chemokine system has a critical role in tumorigenesis and metastasis. The acquisition of stem-like properties by cancer cells is involved in metastasis and drug resistance, which are pivotal problems that result in poor outcomes in patients with lung cancer. Patients with advanced lung cancer present high plasma levels of transforming growth factor-β1 (TGFβ1), which correlate with poor prognostic features. Therefore, TGFβ1 may be important in the tumor microenvironment, where chemokines are widely expressed. However, the role of chemokines in TGFβ1-induced tumor progression still remains unclear. In our study, TGFβ1 upregulated CXC chemokine receptor expression, migration, invasion, epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was the most upregulated chemokine receptor induced by TGFβ1. CXCR7 knockdown resulted in reduction of migration, invasion and EMT induced by TGFβ1, whereas CXCR4 knockdown did not reverse TGFβ1-promoted EMT. CXCR7 silencing significantly decreased cancer sphere-forming capacity, stem-like properties, chemoresistance and TGFβ1-induced CSC tumor initiation in vivo. In clinical samples, high TGFβ1 and CXCR7 expression was significantly associated with the late stages of lung adenocarcinoma. Moreover, TGFβ1 and CXCR7 coexpression was positively correlated with the CSC marker, CD44, which is associated with lymph node metastasis. Besides, patients with high expression of both CXCR7 and TGFβ1 presented a significantly worse survival rate. These results suggest that the TGFβ1-CXCR7 axis may be a prognostic marker and may provide novel targets for combinational therapies to be used in the treatment of advanced lung cancer in the future.

Unlabelled: About 1051 endophytic fungi were isolated from leaves, branches, barks and stems of Cephalotaxus hainanensis Li from four sites in Hainan, China. The fungi were identified as 21 genera by morphology and ITS sequences. One dominant species was Phomopsis quercella in Hainan Tropical Botanical Garden and Bawangling Nature Reserve, with relative frequency of 42·06 and 34·88% respectively. Another dominant species was Colletotrichum boninense in Wuzhishan and Jianfengling Nature Reserves, with relative frequency of 36·84 and 46·97% respectively. Among the selected 21 endophytic fungi, 17 strains (80·95%) had activity against at least one pathogenic bacteria, and 14 strains (66·67%) exhibited activity against at least one fungal pathogens. Neonectria macroconidialis showed strong inhibition against Staphylococcus aureus (inhibition zone being 20 mm), Bacillus subtilis (14 mm) and Streptococcus agalactiae (28 mm). Xylaria sp. showed strong inhibition against Escherichia coli (20 mm), Rhizoctonia solani (20 mm) and Sclerotinia sclerotiorum (17 mm). Verticillium bulbillosum showed great activity against Strep. agalactiae (32 mm) and Fusarium oxysporum (22 mm). These endophytic fungi showed potentials in medicine development., Significance and Impact of the Study: Endophytic fungi from medicinal plants are an important source of novel and viable drugs. Cephalotaxus hainanensis Li is well known for leukaemia treatment and its endophytic fungi were isolated to investigate the diversity and antimicrobial activity. It was found that Ce. hainanensis Li had rich endophytic fungi, and some fungi showed strong antimicrobial activity against certain pathogens. These fungi can be used in medicine development., (© 2015 The Society for Applied Microbiology.)

A novel water-stable open poly-nuclear Cu(I)-based metal-organic framework, [NC2H8]4Cu5(BTT)3·xG (G = guest of DMA and H2O) (1), featuring a giant multi-prismatic nanoscale cage and high CO2/N2 and CO2/H2 sorption selectivities, was successfully assembled by using the nitrogen-rich ligand of 1,3,5-tris(2H-tetrazol-5-yl)benzene (H3BTT) to bridge two types of Cu3 and Cu2 clusters.

Background: Although exercise has been addressed as an adjuvant treatment for anxiety, depression and cancer-related symptoms, limited studies have evaluated the effectiveness of exercise in patients with lung cancer., Methods: We recruited 116 patients from a medical centre in northern Taiwan, and randomly assigned them to either a walking-exercise group (n=58) or a usual-care group (n=58). We conducted a 12-week exercise programme that comprised home-based, moderate-intensity walking for 40 min per day, 3 days per week, and weekly exercise counselling. The outcome measures included the Hospital Anxiety and Depression Scale and the Taiwanese version of the MD Anderson Symptom Inventory., Results: We analysed the effects of the exercise programme on anxiety, depression and cancer-related symptoms by using a generalised estimating equation method. The exercise group patients exhibited significant improvements in their anxiety levels over time (P=0.009 and 0.006 in the third and sixth months, respectively) and depression (P=0.00006 and 0.004 in the third and sixth months, respectively) than did the usual-care group patients., Conclusions: The home-based walking exercise programme is a feasible and effective intervention method for managing anxiety and depression in lung cancer survivors and can be considered as an essential component of lung cancer rehabilitation.

Setting: Taiwan., Objective: To determine factors associated with tuberculosis (TB) reported after death., Design: A retrospective cohort study was conducted of TB patients newly registered between 2006 and 2008. The national TB database was linked with the Vital Registry System and National Health Insurance database for analysis., Results: A total of 1409 (4.0%) TB cases were reported after death. Age ⩾75 years (OR 1.70), chest X-ray (CXR) unknown or not performed (OR 2.41), positive sputum bacteriology (OR 1.74), and comorbidities such as cancer (OR 1.21), chronic liver disease (OR 1.21) and chronic kidney disease (OR 2.58) were associated with the reporting of TB cases after death. More than 30% of TB deaths in elderly persons with chronic kidney disease were TB cases that were reported after death. Abnormal CXR and comorbidities such as chronic obstructive pulmonary disease, stroke and diabetes mellitus were less likely to be associated with the reporting of TB cases after death., Conclusions: Elderly patients with cancer, chronic liver disease or chronic kidney disease require more attention to prevent delayed diagnosis and early mortality from TB. Elderly patients with chronic kidney disease are at highest risk.

Statin and antiplatelet drugs are widely used for prevention of ischaemic stroke and other cardiovascular diseases in high-risk patients. We report a rare case of a 49-year old man with a history of myocardial infarction and hyperlipidaemia who suffered an acute occlusion of his innominate artery (IA) accompanied by subclavian steal syndrome and cerebral infarction, on day seven after abrupt cessation of aspirin and statin, as confirmed by magnetic resonance and computed tomographic angiography of head and neck, and colour-coded Duplex ultrasonography (CCDU). Aspirin and atorvastatin were immediately re-started on admission. Spontaneous recanalization of IA was shown on repeat CCDU and digital subtraction angiography on day 10 after stroke onset. This case serves as a reminder that abrupt discontinuation of both aspirin and statin in patients with previous history of cardiovascular disease may increase the risk of ischaemic stroke.

Hypoxia inducible factor 2α (HIF-2α) is critical for primordial germ cell (PGC) survival as knockout of HIF-2α (HIF-2α(-/-)) decreases both expression of Oct-4 and PGC number in genital ridge. Hypoxia is known to stabilize HIF-2α protein from proteasomal degradation. However, little is known about the hypoxia-associated endocrinal signaling in HIF-2α expression. The current work demonstrates a role for an endocrine insulin-like growth factor-I receptor (IGF-IR)-PI3K/Akt-mTOR-HIF-2α regulatory loop in the proliferation and Oct-4 maintenance of PGC-like alkaline phosphatase positive mouse germline stem cells (AP(+)GSCs). We found that hypoxia greatly increased the cell proliferation and the levels of nuclear Oct-4/HIF-2α protein of AP(+)GSCs. The hypoxic-AP(+)GSCs presented stronger stemness ability for germ cell differentiation than normoxic, with expressions of c-KIT (differentiation germ cell marker), VASA (differentiation germ cell marker) and SCP3 (meiotic marker) using a renal capsule transplantation assay. Meanwhile, hypoxia significantly increased the expression levels of secreted-IGF-I and IGF-IR. The IGF-I dose dependently increased the HIF-2α expression levels in AP(+)GSCs; and, the inhibition of IGF-IR by RNA interference (shIGF-IR) or LY294002 (PI3K inhibitor)/Rapamycin (mTOR inhibitor) effectively suppressed the IGF-I- and/or hypoxia-induced HIF-2α and Oct-4 expression, suggesting that the IGF-IR and its downstream Akt/mTOR signaling are involved in the IGF-I/hypoxia effects. Additionally, knockdown of HIF-2α dramatically suppressed Oct-4 and IGF-IR protein levels in AP(+)GSC cells. In conclusion, the present study demonstrates a regulatory loop of IGF-IR-PI3K/Akt-mTOR-HIF-2α in proliferation and Oct-4 maintenance of PGC-like AP(+)GSCs under hypoxia. This finding provides insights into the niche endocrinology underlying early germ cell development., (© The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

4β-Hydroxywithanolide E is a bioactive withanolide extracted from Physalis peruviana. 4β-Hydroxywithanolide E caused reactive oxygen species production and cell apoptosis in human breast cancer MCF-7 cells. We further found that 4β-hydroxywithanolide E induced DNA damage and regulated the DNA damage signaling in MCF-7 cells. The DNA damage sensors and repair proteins act promptly to remove DNA lesions by 4β-hydroxywithanolide E. The ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway is involved in 4β-hydroxywithanolide E-induced apoptosis of MCF-7 cells. Non-homologous end joining pathway, but not homologous recombination, is the major route of protection of MCF-7 cells against 4β-hydroxywithanolide E-induced DNA damage. 4β-Hydroxywithanolide E had no significant impact on the base excision repair pathway. In this study, we examined the 4β-hydroxywithanolide E-induced DNA damage as a research tool in project investigating the DNA repair signaling in breast cancer cells. We also suggest that 4β-hydroxywithanolide E assert its anti-tumor activity in carcinogenic progression and develop into a dietary chemopreventive agent., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study comprises two trials that investigated the effects of feeding time and time-restricted feeding on the fattening traits and plasma metabolite levels of White Roman geese. In Trial I, 24 geese aged 8 weeks of each sex were allowed free access to a fattening diet for 1 h either in the morning (morning-feeding group) or afternoon (afternoon-feeding group). At 12 weeks of age, blood samples were collected hourly for 4 h, beginning 1 h after feeding to determine the plasma levels of glucose, triacylglycerols and uric acid. The results showed a lower (P<0.05) daily feed intake (DFI) and daily gain (DG) and higher (P<0.05) feed efficiency (FE) for the morning-feeding group compared with those of the afternoon-feeding group. In addition, the postprandial plasma levels of glucose, triacylglycerols and uric acid did not differ (P>0.05) between groups. In Trial II, 12 geese aged 8 weeks of each sex were randomly assigned to either the ad libitum feeding group (control group) or time-restricted feeding group (restricted group). The geese in the control group were fed a fattening diet ad libitum, whereas those in the restricted group were allowed access to the diet for 2 h every morning. All geese were killed at 13 weeks of age and their carcass traits were evaluated. The results showed a lower DFI and DG and higher FE for the restricted group compared with those of the control group (P<0.05). In addition, the restricted group exhibited lower visceral and abdominal fat and higher empty digestive tract and liver weights than those of the control group (P<0.05). The results showed that time-restricted feeding in the morning resulted in superior DG and FE compared with feeding in the afternoon. Moreover, time-restricted feeding implemented in the morning during the fattening period reduced DFI and increased FE in geese compared with ad libitum feeding.