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To evaluate the Vaccine Effectiveness (VE) of the Influenza Vaccine (InfV) during pregnancy in Gansu province. A retrospective cohort of pregnant women vaccinated with InfV was constructed using the electronic case system and immunization planning system of Gansu province. Outcome information of Influenza-Like Illness (ILI) in pregnant women after vaccination with InfV during the influenza epidemic seasons from 2019 to 2021 was collected. The log-binomial model was used to estimate the adjusted Risk Ratio ( RR ), VE, and their Confidence Intervals ( CI ). The incidence rates of the InfV vaccination group and the non-vaccination group during pregnancy in Gansu province were 4.70% (54/1,150) and 6.91% (16,990/245,754), respectively. The adjusted RR was 0.78 (95% CI 0.43-0.75), and the adjusted VE was 22.20 (95% CI 0.79-40.30). Vaccination with InfV during pregnancy in Gansu province from 2019 to 2021 has a protective effect against ILI in pregnant women, and there is no difference in vaccination at different stages of pregnancy.

The detrimental impact of noise on sensing performance in quantum metrology has been widely recognized by researchers in the field. However, there are no explicit fundamental laws of physics stating that noise invariably weakens quantum metrology. We reveal that phase-covariant noise either degrades or remains neutral to sensing precision, whereas non-phase-covariant noise can potentially enhance parameter estimation, surpassing even the ultimate precision limit achievable in the absence of noise. This implies that a non-Hermitian quantum sensor may outperform its Hermitian counterpart in terms of sensing performance. To illustrate and validate our theory, we present several paradigmatic examples of magnetic field metrology.

Background: Hepatitis B, often leading to Hepatocellular carcinoma (HCC), poses a major global health challenge. While Tenofovir (TDF) and Entecavir (ETV) are potent treatments, their comparative effectiveness in improving recurrence-free survival (RFS) and overall survival (OS) rates in HBV-related HCC is not well-established. Methods: We conducted an individual patient data meta-analysis using survival data from randomized trials and high-quality propensity score-matched studies to compare the impact of Tenofovir (TDF) and Entecavir (ETV) on RFS and OS in HBV-related HCC patients. Data from six databases and gray literature up to 30 August 2023, were analyzed, utilizing Kaplan-Meier curves, stratified Cox models, and shared frailty models for survival rate assessment and to address between-study heterogeneity. The study employed restricted mean survival time analysis to evaluate differences in RFS and OS between TDF-treated and ETV-treated patients. Additionally, landmark analyses compared early (<2 years) and late (≥2 years) tumor recurrence in these cohorts. Results: This study incorporated seven research articles, covering 4,602 patients with HBV-related HCC (2,082 on TDF and 2,520 on ETV). Within the overall cohort, TDF recipients demonstrated significantly higher RFS ( p = 0.042) and OS ( p < 0.001) than those on ETV. The stratified Cox model revealed significantly improved OS for the TDF group compared to the ETV group (hazard ratio, 0.756; 95% confidence interval, 0.639-0.896; p = 0.001), a result corroborated by the shared frailty model. Over a follow-up period of 1-8 years, no significant difference was noted in the mean time to death between the TDF and ETV groups. The rates of early recurrence did not significantly differ between the groups ( p = 0.735). However, TDF treatment was significantly associated with a reduced risk of late recurrence compared to ETV ( p < 0.001). In the HCC resection subgroup, the disparities in OS, early, and late recurrence rates between the two treatments paralleled those seen in the overall cohort. Conclusion: Compared to ETV, TDF may enhance OS and reduce late tumor recurrence risk in HBV-related HCC patients receiving curative treatment. However, there was no statistically significant distinction in the timing of tumor recurrence and mortality between patients administered TDF and those prescribed ETV. Systematic Review Registration: http://www.crd.york.ac.uk/prospero/., 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 © 2024 Peng, Wang, Wang, Li, Lin and He.)

Ecological security pattern is an important spatial way to maintain ecological processes and ensure the stability of ecosystem functions. As the implementation of landscape planning and decision-making, it is critically needed to consider the consistency of differentiated methods and their spatial outputs in the construction of ecological security patterns and the matching and applicability of research objects. From the perspective of integration, we combined the regional topography and landscape characteristics, integrated the morphological spatial pattern analysis and the importance evaluation results of ecosystem services to identify the ecological source, and constructed the ecological security pattern of the Ansai District of Yan'an City, the main implementation area of the Grain-for-Green Project on the Loess Plateau. The results showed that the structural and functional construction methods had low consistency in the identification of spatial protection priority. The integration-oriented method could complement each other and achieve the dual goals of structural connectivity and functional improvement. There were 202 ecological sources in the study area, with a total area of 391.58 km 2 , accounting for 13.3% of the total area of the study area. There were 110 ecological corridors in the study area, with a total length of 599 km, which were mainly distributed around the river channel, showing a distribution pattern of 'short and narrow dense in the north and south, long and wide in the middle'. The structure-function integration method provides new insights for ecological restoration planning of land space and promotes the research of landscape pattern, process and service.

We theoretically investigate continuous variable entanglement and macroscopic quantum coherence in the hybrid L-G rotational cavity optomechanical system containing two YIG spheres. In this system, a single L-G cavity mode and both magnon modes (which are due to the collective excitation of spins in two YIG spheres) are coupled through the magnetic dipole interaction whereas the L-G cavity mode can also exchange orbital angular momentum (OAM) with the rotating mirror (RM). We study in detail the effects of various physical parameters like cavity and both magnon detunings, environment temperature, optorotational and magnon coupling strengths on the bipartite entanglement and the macroscopic quantum coherence as well. We also explore parameter regimes to achieve maximum values for both of these quantum correlations. We also observed that the parameters regime for achieving maximum bipartite entanglement is completely different from macroscopic quantum coherence. So, our present study shall provide a method to control various nonclassical quantum correlations of macroscopic objects in the hybrid L-G rotational cavity optomechanical system and have potential applications in quantum sensing, quantum meteorology, and quantum information science., (© 2024. The Author(s).)

Objective: The objective was to present our experience on managing mycotic infrarenal abdominal aortic aneurysm (MIAAA) through a retrospective cohort study., Methods: Data of patients with MIAAA managed in our center from July 2016 to October 2022 were retrospectively analyzed. The diagnosis of MIAAA was made based on: (1) preoperative clinical signs of infection; (2) elevated serologic infection parameters; (3) para-aneurysmal infection features on enhanced computed tomography; and (4) positive blood or tissue cultures. All the patients received standard antibiotic therapy. Surgical management including endovascular aneurysm repair (EVAR), initial EVAR followed by open re-operation, and initial open surgical repair (OSR) were conducted according to disease seriosity, physical condition, and patient's will. Infection index and clinical outcome were evaluated during the follow-up time., Results: A total of 23 patients (21 men; averaged=66.3 years, range=49-79 years) were included, with a mean follow-up time of 19.9 months (range=1-75 months). Bacteria culture from blood or tissue specimen was positive in 15 patients ( Salmonella , n=8; Escherichia coli , n=3; methicillin-sensitive Staphylococcus aureus [MSSA], n=1; Klebsiella pneumoniae , n=1; Staphylococcus epidermidis , n=1; Mycobacterium tuberculosis , n=1). Seven patients received OSR as the initial surgical intervention, whereas 14 patients chose EVAR instead. The 2 conservatively managed patients (refused surgery) died within 30 days. The 7 patients who received initial OSR survived till now. Among the 14 patients who underwent initial EVAR, infection deteriorated without exception (14/14, 100%). Three of these patients refused re-operation and died within 6 months. Eleven patients received secondary surgical intervention (10 cases of aneurysm and endograft resection, thorough debridement, subclavian to bi-femoral artery bypass, or in situ aorta reconstruction; 1 case of laparoscopic debridement) and 7 survived the follow-up time. The overall mortality rate was 39.1% (9/23). The mortality rates differed greatly following different intervention methods (merely antibiotic management, 100%; initial open operation, 0%; initial EVAR without secondary operation, 100%; initial EVAR plus secondary operation, 36.4%)., Conclusions: Open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely EVAR is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary OSR., Clinical Impact: The management of mycotic or primary-infected aortic aneurysm is challenging; treatment remains controversial. Our center has reviewed our experience over the past 6 years and found that open surgical repair is still the first choice for hemodynamically stable and low-risk patients. Merely endovascular aneurysm repair (EVAR) is related with disastrous results, which should be reserved as a temporary alternative for patients with ruptured aneurysms, hemodynamic instability or high surgical risk, and followed by timely secondary open surgical repair., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare.

A scheme is proposed to achieve significantly enhanced quantum estimation of optorotational-coupling (ORC) strength by coupling a driven auxiliary cavity to a Laguerre-Gaussian (L-G) rotational cavity, where the ORC originates from the exchange of orbital angular momentum between a L-G light and rotational mirror. The results indicate that, by appropriately designing the auxiliary-cavity mechanism, the estimation error of the ORC parameter is significantly reduced, and revealing the estimation precision has a much stronger thermal noise and dissipation robustness in comparison with the unassisted case. Our study paves the way toward achieving high-precision quantum sensors.

Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO 2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO 2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO 2 nanosheets to Mn 2+ , resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans -cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL -1 . In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.

We theoretically propose a scheme to generate distant bipartite entanglement between various subsystems in coupled magnomechanical systems where both the microwave cavities are coupled through single photon hopping coupling strength Γ. Each cavity contains a magnon mode and phonon mode and this gives six excitation modes in our model Hamiltonian which are cavity-1 photons, cavity-2 photons, magnon and phonon in cavity-1, and magnon and phonon in cavity-2. We found that significant bipartite entanglement exists between indirectly coupled subsystems in coupled microwave cavities for an appropriate set of parameters regime. Moreover, we also obtain suitable cavity and magnon detuning parameters for a significant distant bipartite entanglement in different bipartitions. In addition, it can be seen that a single photon hopping parameter significantly affects both the degree as well as the transfer of quantum entanglement between various bipartitions. Hence, our present study related to coupled microwave cavity magnomechanical configuration will open new perspectives in coherent control of various quantum correlations including quantum state transfer among macroscopic quantum systems., (© 2023. The Author(s).)

The roles of cyclin-dependent kinase 6 (CDK6) in various cancers, including small cell lung carcinoma (SCLC), remain unclear. Here, 111,54 multi-center samples were investigated to determine the expression, clinical significance, and underlying mechanisms of CDK6 in 34 cancers. The area under the curve (AUC), Cox regression analysis, and the Kaplan-Meier curves were used to explore the clinical value of CDK6 in cancers. Gene set enrichment analysis and correlation analysis were performed to detect potential CDK6 mechanisms. CDK6 expression was essential in 24 cancer cell types. Abnormal CDK6 expression was observed in 14 cancer types (e.g., downregulated in breast invasive carcinoma; p < 0.05). CDK6 allowed six cancers to be distinguished from their controls (AUC > 0.750). CDK6 expression was a prognosis marker for 13 cancers (e.g., adrenocortical carcinoma; p < 0.05). CDK6 was correlated with several immune-related signaling pathways and the infiltration levels of certain immune cells (e.g., CD8 + T cells; p < 0.05). Downregulated CDK6 mRNA and protein levels were observed in SCLC (p < 0.05, SMD = - 0.90). CDK6 allowed the identification of SCLC status (AUC = 0.91) and predicted a favorable prognosis for SCLC patients (p < 0.05). CDK6 may be a novel biomarker for the prediction and prognosis of several cancers, including SCLC., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Paeonol (PAE) is a natural phenolic monomer isolated from the root bark of Paeonia suffruticosa that has been widely used in the clinical treatment of some inflammatory-related diseases and cardiovascular diseases. Much preclinical evidence has demonstrated that PAE not only exhibits a broad spectrum of anticancer effects by inhibiting cell proliferation, invasion and migration and inducing cell apoptosis and cycle arrest through multiple molecular pathways, but also shows excellent performance in improving cancer drug sensitivity, reversing chemoresistance and reducing the toxic side effects of anticancer drugs. However, studies indicate that PAE has the characteristics of poor stability, low bioavailability and short half-life, which makes the effective dose of PAE in many cancers usually high and greatly limits its clinical translation. Fortunately, nanomaterials and derivatives are being developed to ameliorate PAE's shortcomings. This review aims to systematically cover the anticancer advances of PAE in pharmacology, pharmacokinetics, nano delivery systems and derivatives, to provide researchers with the latest and comprehensive information, and to point out the limitations of current studies and areas that need to be strengthened in future studies. We believe this work will be beneficial for further exploration and repurposing of this natural compound as a new clinical anticancer drug., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association., Materials and Methods: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode., Results: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05)., Conclusion: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases., (© 2023. The Japanese Society Bone and Mineral Research.)

Phaeocystis is a globally distributed Prymnesiophyte genus and usually forms massive harmful colony blooms, which impact marine ecosystem, mariculture, human health, and even threaten coastal nuclear power plant safety. However, the mechanisms behind the colony formation from the solitary cells remain poorly understood. Here, we investigated metabolic processes of both solitary and non-flagellated colonial cells of Phaeocystis globosa at different colony bloom stages in the subtropical Beibu Gulf using a metaproteomic approach. Temperature was significantly correlated with Phaeocystis colony bloom formation, and the flagellated motile solitary cells with abundant flagellum-associated proteins, such as tubulin and dynein, were the exclusive cellular morphotype at the solitary cell stage featured with temperatures ≥21 °C. When the temperature decreased to <21 °C, tiny colonies appeared and the flagellum-associated proteins were down-regulated in both solitary and non-flagellated colonial cells, while proteins involved in biosynthesis, chain polymerization and aggregation of glycosaminoglycan (GAG), a key constituent of gelatinous matrix, were up-regulated, indicating the central role of active GAG biosynthesis during the colony formation. Furthermore, light utilization, carbon fixation, nitrogen assimilation, and amino acid and protein synthesis were also enhanced to provide sufficient energy and substrates for GAG biosynthesis. This study highlighted that temperature induced re-allocation of energy and substances toward GAG biosynthesis is essential for colony bloom formation of P. globosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Although the morphological changes of sella turcica have been drawing increasing attention, the acquirement of linear parameters of sella turcica relies on manual measurement. Manual measurement is laborious, time-consuming, and may introduce subjective bias. This paper aims to develop and evaluate a deep learning-based model for automatic segmentation and measurement of sella turcica in cephalometric radiographs., Methods: 1129 images were used to develop a deep learning-based segmentation network for automatic sella turcica segmentation. Besides, 50 images were used to test the generalization ability of the model. The performance of the segmented network was evaluated by the dice coefficient. Images in the test datasets were segmented by the trained segmentation network, and the segmentation results were saved in binary images. Then the extremum points and corner points were detected by calling the function in the OpenCV library to obtain the coordinates of the four landmarks of the sella turcica. Finally, the length, diameter, and depth of the sella turcica can be obtained by calculating the distance between the two points and the distance from the point to the straight line. Meanwhile, images were measured manually using Digimizer. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to analyze the consistency between automatic and manual measurements to evaluate the reliability of the proposed methodology., Results: The dice coefficient of the segmentation network is 92.84%. For the measurement of sella turcica, there is excellent agreement between the automatic measurement and the manual measurement. In Test1, the ICCs of length, diameter and depth are 0.954, 0.953, and 0.912, respectively. In Test2, ICCs of length, diameter and depth are 0.906, 0.921, and 0.915, respectively. In addition, Bland-Altman plots showed the excellent reliability of the automated measurement method, with the majority measurements differences falling within ± 1.96 SDs intervals around the mean difference and no bias was apparent., Conclusions: Our experimental results indicated that the proposed methodology could complete the automatic segmentation of the sella turcica efficiently, and reliably predict the length, diameter, and depth of the sella turcica. Moreover, the proposed method has generalization ability according to its excellent performance on Test2., (© 2023. The Author(s).)

Background: At present, studies on MircoRNA-22-3p (miR-22-3p) in lung adenocarcinoma use a single method, lack multi-center validation and multi-method validation, and there is no big data concept to predict and validate target genes., Objective: To investigate the expression, potential targets and clinicopathological significance of miR-22-3p in lung adenocarcinoma (LUAD) tissues., Methods: LUAD formalin-fixed paraffin-embedded (FFPE) tumors and adjacent normal lung tissues were collected for real-time quantitative polymerase chain reaction (RT-qPCR). Collect miR-22-3p in LUAD and non-cancer lung tissue from high-throughput datasets, standardized mean difference (SMD) and area under the curve (AUC) of the comprehensive receiver operating curve (summary receiver operating characteristic cure, sROC curve) were calculated. Cell function experiments on A549 cells transfected with LV-hsa-miR-22-3p. Target genes were predicted by the miRwalk2.0 website and the resulting target genes were subjected to Gene Ontology (GO) pathway enrichment analysis and constructed to protein-protein interaction network. Finally, the protein expression level of the key gene TP53 was validated by searching The Human Protein Atlas (THPA) database to incorporate TP53 immunohistochemical results in LUAD., Results: RT-qPCR result from 41 pairs of LUAD and adjacent lung tissues showed that miR-22-3p was downregulated in LUAD (AUC = 0.6597, p= 0.0128). Globally, a total of 838 LUADs and 494 non-cancerous lung tissues were included, and were finally combined into 14 platforms. Compared with noncancerous tissue, miR-22-3p expression level was significantly reduced in LUAD tissue (SMD =-0.32, AUC = 0.72l); cell function experiments showed that miR-22-3p has inhibitory effects on cell proliferation, migration and invasion, and has promotion effect on apoptosis. Moreover, target genes prediction, GO pathway enrichment analysis and PPI network exhibited TP53 as a key gene of target gene of miR-22-3p; at last, a total of 114 high-throughput datasets were included, including 3897 LUADs and 2993 non-cancerous lung tissues, and were finally combined into 37 platforms. Compared with noncancerous tissue, TP53 expression level was significantly increased in LUAD (SMD = 0.39, p< 0.01) and it was verified by the protein expression data from THPA., Conclusion: Overexpression of miR-22-3p may inhibit LUAD cell proliferation, migration and invasion through TP53, and promote cell apoptosis.

Purpose: To use statistical process control for intensity-modulated radiation therapy (IMRT) quality assurance (QA) and improve tolerance limits and action limits., Methods: An electronic portal imaging device (EPID) was selected to verify IMRT QA. The I-chart and the exponentially weighted moving averages (EWMA) chart were used to analyze the corresponding results., Results: Twenty samples were used to enable the sampling requirements for building the control limits to be met. The I-chart showed that isolated data points beyond the control limits were mainly derived from complex plans. The EWMA made predictions of systematic errors earlier than the I-chart. Systematic errors primarily originated from the dose calibration on the EPID, and recalibrating the EPID could eliminate such errors., Conclusion: Statistical process control is an effective tool to detect controllable and can be used in IMRT QA. After calibrating the EPID, the tolerance and action limits all improved and satisfied the requirements/recommended values of the AAPM TG-218 report., (Copyright © 2021. Published by Elsevier Masson SAS.)

Since there are no corresponding specification limits for some new daily quality assurance (QA) items in the TG-142, it is a compromise that the specification limits used in the monthly or annual QA procedures are used for the daily QA procedure in work. But there is no basis for whether this is feasible. The purpose of this article is to analyze QA results using SPC to determine the tolerance limits at our institution, and to present the usefulness of the analysis method using SPC. The data of three groups daily QA processes performed with Daily QA3 in three years were analyzed using statistical process control (SPC). For calculating capability indices (Cp, Cpk, Cpm and Cpmk) of processes, the appropriate number of calculation points was analyzed firstly. Then, in calculating the capability indices for output, limits ±3% of the daily QA in the TG-142 were used as the specification limit, while for flatness and symmetry, an annual QA limits of ±1% was used. For putting forward measures to solve the problem, customized tolerance and action limits were established for each process. And the process control charts calculated using data measured by the five therapists and a medical physicist were compared. At least six to eight weeks of control daily check data points (i.e. 30-40 points) should be used for calculating the individuals and moving range (I-MR) control chart to ensure the stability of control lines. Process capability indices of output were all ≥1, some were up to 3-4. While for symmetry, some processes failed to meet the requirements that capability indices were < 1. For different processes of the same daily QA items, the calculated customized limits were quite different. The range of upper control line (UCL) and lower control line (LCL) was smaller for output and the CL was closer to the target value of 0 for flatness and symmetry in the I-MR control chart calculated using data measured by one staff. For different quality control processes without management by the SPC method at our institution, calculated tolerance and action limits of the same measurement item were quite different. And in most measurement items, the specification limits used in the monthly or annual QA procedures in the TG-142 are not suitable to the daily QA procedure. So the analysis method using SPC is useful and necessary., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose: This study was carried out to investigate brain functional connectome and its potential relationships with the disease severity and emotion function in patients with essential tremor with and without depressive symptoms by using resting-state functional magnetic resonance imaging and graph theory approaches., Methods: In this study 33 essential tremor patients with depression, 45 essential tremor patients without depression and 79 age and gender-matched healthy controls were recruited to undergo a 3.0‑T imaging scan. The whole brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions, and the topologic properties were analyzed by using graph theory approaches and network-based statistic approaches. Nonparametric permutation test was also used for group comparisons of topological metrics. Correlation analyses between topographic features and the clinical characteristics were performed., Results: The functional connectome in both essential tremor patients with and without depression showed abnormalities at the global level (decrease in clustering coefficient, global efficiency, and local efficiency but increase in characteristic path length) and at the nodal level (decrease nodal centralities in the cerebellum, motor cortex, prefrontal-limbic regions, default mode network) (p < 0.05, false discovery rate corrected). Moreover, essential tremor patients with depression showed higher node efficiency in superior frontal gyrus and posterior cingulate gyrus compared to essential tremor without depression., Conclusion: Our results may provide insights into the underlying pathophysiology of essential tremor patients with and without depression and aid the development of some potential biomarkers of the depressive symptoms in patients with essential tremor., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: PINK1 mutations are the second most common cause of recessive, early-onset Parkinson's disease (EOPD), of which 15% are cases of juvenile PD. PD is a progressive neurological disease that primarily affects middle-aged and older people. Thus PD patients experiencing pregnancy is uncommon, especially in patients with juvenile PD caused by PINK1 mutations. We are first to report a woman from a Chinese family diagnosed with sporadic juvenile PD and treated with levodopa/benserazide throughout pregnancy., Methods: Whole exome sequencing was performed on this patient, and pedigree verification was performed on her parents. This patient received levodopa/benserazide treatment with regular outpatient follow-up exams., Results: Whole exome sequencing and Sanger sequencing identified a heterozygous nonsense mutation (c.1474C > T, p.R492X) and a splicing mutation (c.1488 + 1G > A) that were in exon 7 of the PINK1 gene, co-segregating with the PD phenotype and exhibiting an autosomal recessive pattern. With regular outpatient follow-up exams, this patient delivered a healthy boy without complications. Her PD symptoms were stable with the levodopa/benserazide treatment throughout her pregnancy except in the postpartum period., Conclusion: Our findings further demonstrated the safety of levodopa with dopa-decarboxylase treatment in PINK1-associated juvenile PD during pregnancy.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 is challenging the dental community to an unprecedented degree. Knowledge of the increased risk of infection in dental settings has been disseminated to the public and guidelines have been formulated to assist dental attendance decision-making. However, dental attendance behaviors incompatible with treatment need is not uncommon in clinical settings. Important gaps remain in the knowledge about how psychological factors are affecting dental attendance behaviors during the COVID-19 epidemic. In this cross-sectional study, a questionnaire survey was performed during February and March 2020. A total of 342 and 294 dental patients who attended and avoided dental visits, respectively, were included. The participants were classified into four groups based on dental attendance behavior and emergent/urgent dental treatment need. Bivariate analysis was performed to investigate factors associated with dental attendance. Multivariable logistic regression based on principal component scores was performed to identify major psychological constructs associated with unnecessary dental avoidance and attendance. Among all the factors explored, inability to wear masks during dental treatment ( P < 0.001; effect size: 0.32) was most closely associated with the overall pattern of dental attendance among participants. Multivariable regression suggested that unnecessary dental avoidance was associated with perceived risk of infection in general and in dental settings (odds ratio [95% CI]: 0.62 [0.53, 0.72]; p < 0.001), perceived impact of COVID-19 and dental problems on general health (0.79 [0.65, 0.97]; 0.021), and personal traits such as trust and anxiety (0.77 [0.61, 0.98]; 0.038). Unnecessary dental attendance was associated with optimism toward the epidemic (1.68 [1.42, 2.01]; <0.001) and trust (1.39 [1.13, 1.74]; 0.002). Multidisciplinary efforts involving dental and medical professionals as well as psychologists are warranted to promote more widespread adoption, among the general public, of dental attendance behaviors compatible with dental treatment need during the COVID-19 epidemic., 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. The reviewer MZ declared a shared affiliation with several of the authors, PF, SW, and XL, to the handling editor at time of review., (Copyright © 2021 Wen, Fang, Peng, Wu, Liu and Dong.)

Background: IGF-1 may be an important factor in bone remodeling, but its mechanism of action on osteoclasts during orthodontic tooth movement is complex and unclear., Methodology: The closed-coil spring was placed between the left maxillary first molar and upper incisors with a force of 50 g to establish an orthodontic movement model. Eighty SD rats were randomized to receive phosphate buffer saline or 400 ng rhIGF-1 in the lateral buccal mucosa of the left maxillary first molar every two days. Tissue sections were stained for tartrate-resistant acidic phosphatase (TRAP), the number of TRAP-positive cells was estimated and tooth movement measured., Results: The rhIGF-1 group exhibited evidential bone resorption and lacuna appeared on the alveolar bone compared to the control group. Moreover, the number of osteoclasts in compression side of the periodontal ligament in the rhIGF-1 group peaked at day 4 (11.37±0.95 compared to 5.28±0.47 in the control group) after the orthodontic force was applied and was significantly higher than that of the control group (p<0.01). Furthermore, the distance of tooth movement in the rhIGF-1 group was significantly larger than that of the control group from day 4 to day 14 (p<0.01), suggesting that rhIGF-1 accelerated orthodontic tooth movement., Conclusion: Our study has showed that rhIGF-1 could stimulate the formation of osteoclasts in the periodontal ligament, and accelerate bone remodeling and orthodontic tooth movement.

Objectives: Essential tremor with resting tremor (rET) often exhibits severer clinical features and more extensive functional impairment than essential tremor without resting tremor (ETwr). However, the pathophysiology of rET is still unclear. This study aims to use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the alterations of brain activity between the drug-naïve patients of rET and ETwr., Methods: We recruited 19 patients with rET, 31 patients with ETwr and 25 healthy controls (HCs) to undergo a 3.0-T rs-fMRI examination. The differences of regional brain spontaneous activity between the rET, ETwr and HCs, as well as between total ET (rET + ETwr) and HCs were measured by amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF). The relationships between the altered brain measurements and the clinical scores were analyzed., Results: Compared with HCs, both ET subgroups showed significantly decreased ALFF or fALFF values in the basal ganglia, inferior orbitofrontal gyrus and insula. The rET group specifically showed decreased ALFF values in the hippocampus and motor cortices, while the ETwr group specifically evidenced increased ALFF and fALFF values in the cerebellum., Discussion: Regional spontaneous activity in rET and ETwr share common changes and have differences, which may suggest that the functional activities in the limbic system and cerebellum are different between the two subtypes. Improved insights into rET and ETwr subtypes and the different brain spontaneous activity will be valuable for improving our understanding of the pathophysiology of the disease.

Background: Craniopharyngioma represents a troublesome tumor of the intracranial sellar region. There are currently no available well-characterized craniopharyngioma cell lines. This lack of reliable, immortal cell lines is a major reason for the slow progress in fundamental research related to craniopharyngioma., Methods: We describe the development of an immortal papillary craniopharyngioma (PCP) cell line by transfecting primary PCP cells with the pLenti-simian virus 40 large T antigen(SV40LT)., Results: Three clones have been cultured for more than 14 months so far, while non-transfected cells ceased proliferation within three months of isolation. The established immortal PCP cell lines were identified to have BRAF V600E mutations, while no mutations in tumor suppressor genes were found in primary cells or immortal cells. Immortal cells had higher proliferation rates and formed tumors when implanted in the bran of nude mice. BRAF inhibition in immortal PCP cells altered cell morphology, inhibited cell proliferation and promoted apoptosis., Conclusion: We successfully developed PCP cell lines by SV40LT-mediated immortalization. These cell lines represent a powerful tool for fundamental and therapeutical studies on craniopharyngioma.

Objective: The thalamus is a key node for sleep-wake pathway gate switching during acute sleep deprivation (ASD), and studies have shown that it plays a certain role in emotion changes. However, there are no studies on the association between the thalamus and emotion changes in ASD. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore whether changes in the functional connections between the thalamus and other brain regions are related to emotion changes and further explored the function of the thalamus under total ASD conditions. Method: Thirty healthy, right-handed adult men underwent emotional assessment according to the Profile of Mood States Scale and R-fMRI scans before and after ASD. The correlations between changes in functional connectivity between the thalamus and other brain regions and emotion changes were then studied. Results: Positive emotions and psychomotor performance were reduced, and negative emotions were increased following ASD. The functional connections between the left thalamus and left middle temporal gyrus, left inferior frontal gyrus, right thalamus, right inferior temporal gyrus, left middle temporal pole gyrus, right calcarine, left cuneus, left rectus and left medial superior frontal gyrus were significantly altered. Decreased functional connectivity between left thalamus and left inferior frontal gyrus related to emotion changes following ASD. Conclusion: This study finds that functional changes in the thalamus are associated with emotion changes during ASD, suggesting that the left thalamus probably plays an essential role in emotion changes under ASD conditions., 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 Li, Cao, Zhang, Chen, Gao, Peng, Shao and Zhang.)

The clinical pictures of essential tremor (ET) with resting tremor (rET) and tremor-dominant Parkinson's disease (tPD) are often quite mimic at the early stage, current approaches to the diagnosis and treatment therefore remain challenging. The regional homogeneity (ReHo) method under resting-state functional magnetic resonance imaging (rs-fMRI) would help exhibit the patterns in neural activity, which further contribute to differentiate these disorders and explore the relationship between symptoms and regional functional abnormalities. Sixty-eight Chinese participants were recruited, including 19 rET patients, 24 tPD patients and 25 age- and gender-matched healthy controls (HCs). All participants underwent clinical assessment and rs-fMRI with a ReHo method to investigate the alterations of neural activity, and the correlation between them. Differences were compared by two-sample t-test (corrected with AlphaSim, p < 0.05). Compared with HCs, patients' groups both displayed decreased ReHo in the default mode network (DMN), bilateral putamen and bilateral cerebellum. While tPD patients specifically exihibited decreased ReHo in the bilateral supplementary motor area (SMA) and precentral gyrus (M1). The correlation analysis revealed that ReHo in the bilateral putamen, right SMA and left cerebellum&#95;crus I were negatively correlated with the UPDRS-III score, respectively, in tPD group. Our results indicated the rET patients may share part of the pathophysiological mechanism of tPD patients. In addition, we found disorder-specific involvement of the SMA and M1 in tPD. Such a distinction may lend itself to use as a potential biomarker for differentiating between these two diseases.

Nasopharyngeal carcinoma (NPC) has a distinctive geographical distribution in China, especially southern China. There are several risk factors for NPC, such as Epstein-Barr virus, genetics, and environmental exposures. Although the incidence of eye metastasis (EM) is lower than metastasis in other body parts, it often indicates poor prognosis.We assessed several serum biomarkers for their ability to predict EM in NPC. Patients with NPC were selected (n = 963), and were separated into two groups, EM and no eye metastasis. Ten factors were analyzed in both groups including triglyceride (TG), high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, alpha fetoprotein, carbohydrate antigen-199, cancer antigen-153, apolipoproteins AI, apolipoprotein B, and cytokeratin fragment 19 (CYFRA21-1). Independent t tests, binary logistic regression, and receiver operating characteristic curves were used to assess the data.The EM group had significantly higher CYFRA21-1 and lower TG compared with the no eye metastasis group. Areas under the curve for CYFRA21-1, TG and CYFRA21-1/TG were 0.966, 0.771, and 0.976, respectively. The corresponding cut-off values were 12.12 ng/ml, 0.41 mmol/L, and 13.5. The sensitivity and specificity of CYFRA21-1/TG were 100% and 92.2%, respectively.The increased ratio of CYFRA21-1 to TG can be an accurate method to detect EM in patients with NPC.

Objective: Some patients with paediatric craniopharyngiomas (PCs) showed normal growth despite growth hormone deficiency, which is known as growth without GH (GWGH); however, its mechanism remains unclear. We aimed to develop a novel clinical score to predict the probability of GWGH in PCs., Methods: A total of 708 PC patients were prospectively enrolled from six hospitals, among which 431 patients were finally included. Data from four of the six hospitals (n = 325) were used to develop the innovative clinical score (ICS), which was further validated using the data from the other two hospitals (n = 106). To establish and validate the ICS, sequential logistic regression was used to analyse the clinical characteristics including tumour growth pattern and tumour size and so on. Furthermore, C-statistic was employed to calibrate the discriminatory ability of the established clinical score, while a calibration plot was adopted for further assessment., Results: The overall incidence of GWGH was 16.9% (73/431). The ICS ranged from 2 to 23, with an optimism-corrected C-statistic of 0.820, Furthermore, the optimism-corrected C-statistic of external validation was 0.835, indicating good discriminatory power and robustness of the clinical score. Additionally, no apparent overestimation or underestimation was observed in the calibration plots, which showed excellent calibration power of the clinical score., Conclusions: Based on tumour growth patterns and PC patients' clinical characteristics, individualized surgical strategies were promising to achieve long-term effective management of PC patients. The ICS is valuable for the evaluation of probability of developing postoperative GWGH., Clinical Trial Registration: ClinicalTrials.gov ID: NCT00949156.

Background: Many studies confirm that anatomical resection was associated with favorable oncologic outcomes for patients with HCC who had preserved as much of the remnant liver tissue as possible. 1,2 In recent years, laparoscopic liver resection has been widely extended from minor resection to complex hepatectomy, 3 However, surgery on tumors located in the posterosuperior segment remains a demanding procedure regardless of the extent of resection. 4 Laparoscopic anatomical segment VII resection has one of the highest difficulty scores based on the tumor location due to poor accessibility, hard to exposure, and difficulty in obtaining sufficient surgical margins. 5,6 Here, we report a totally laparoscopic anatomical VII resection using the Glissonian approach with indocyanine green dye fluorescence., Methods: A 74-year-old man with a body mass index of 31.9 kg/m 2 suffered from HBV-related cirrhosis was admitted to our institution. The preoperative Gd-EOB-DTPA MRI showed a 2.7-cm HCC located in segment VIII. The preoperative AFP is 3431 ng/ml. A true anatomical segmentectomy was performed by using selective occlusion of segment VII Glissonian pedicle, which was identified from the liver hilum. Indocyanine green (ICG) dye demarcation was used as a guidance during parenchymal transection., Results: The operative time was 270 min with an estimated blood loss of 200 mL. The postoperative course was uneventful. Drainage tube was pulled out on the fourth day. The pathology confirmed the diagnosis of hepatocellular carcinoma and the surgical margin was negative. The patient was discharged on the 8th day after operation., Conclusions: Totally laparoscopic anatomical segment VII resection is a technically challenging operation. Advanced laparoscopic skills are necessary to complete such a difficult procedure safely. Glissonian approach and ICG fluorescence imaging guide parenchyma resection could be help.

Adamantinomatous craniopharyngioma (ACP) is a benign epithelial tumor of the sellar region. Whether primary human cell cultures can be used as a stable research model has yet to be determined. The characteristics of three cultured craniopharyngioma primary cell (CPC) lines were identified using immunofluorescence. The culture duration for each CPC line was 10, 20 and 30 days. Cell lines and paired parental tumor tissues were subsequently analyzed using transcriptome sequencing (RNA-Seq). Transcriptomic differences between ACP tissues and CPC lines were compared. CPCs maintained the original epithelial lineage markers, including pan-cytokeratin and epithelial cell adhesion molecule. However, the Pearson's correlation coefficient of transcriptomes between each pair of CPC lines and ACP tissues decreased from 0.657 (cultured for 10 days) to 0.61 (cultured for 20 days) and further to 0.547 (cultured for 30 days). The number of differentially expressed genes between ACP tissues and CPCs was increased from 1,247 (cultured for 10 days) to 1,643 (cultured for 20 days) and then to 1,949 (cultured for 30 days). The results of Gene Set Enrichment Analysis demonstrated that the diversity of gene sets increased with longer culture time. Significant differences in the majority of signature gene sets were not observed between ACP tissues and CPCs, with the exception of keratinization phenotype [normalized enrichment score (NES)=-2.02, false discovery rate (FDR)=0.0038] and epithelial cell phenotype (NES=-1.82, FDR=0.032). Cell proliferation (NES=1.78, FDR=0.028) and mitosis (NES=1.93, FDR=0.012) were enhanced in CPCs. Therefore, primary human cell cultures can be used as a suitable research platform for ACP, however further experiments are required., (Copyright: © Zhang et al.)

Objectives: To determine the feasibility of a personalized music intervention with mechanically ventilated patients in the PICU., Design: Pilot study with a quasi-experimental design., Setting: Tertiary children's hospital in China with a 40-bed PICU., Patients: Children, 1 month to 7 years, with mechanical ventilation were recruited and assigned to music group (n = 25) and control group (n = 25)., Interventions: Children in the music group received their own favorite music and listened for 60 minutes three times a day. The control group receive routine care without music., Measurements and Main Results: Primary outcome measure was comfort measured with the COMFORT Behavior scale 5 minutes before and after the music. Secondary outcome measures were physiologic variables; heart rate, respiration, blood pressure, oxygen saturation. Mechanical ventilation time, length of stay, and sedation medication were also collected. Qualitative analysis revealed that nurses had a positive attitude in delivering the interventions and identified improvements for the main trial. Children in the music group had lower COMFORT Behavior scores (15.7 vs 17.6; p = 0.011). Children in the music group had better physiologic outcomes; heart rate (140 vs 144; p = 0.039), respiration rate (40 vs 43; p = 0.036), systolic blood pressure (93 vs 95 mm Hg; p = 0.031), oxygen saturation (96% vs 95%; p < 0.001), diastolic blood pressure was not significantly (52 vs 53 mm Hg; p = 0.11). Children in the music group had a shorter ventilation time (148.7 vs 187.6; p = 0.044) and a shorter length of stay, but not significant (11.2 vs 13.8; p = 0.071). Children in the control group had higher total amount of on-demand midazolam (29 vs 33 mg; p = 0.040)., Conclusions: Our pilot study indicates that personalized music intervention is feasible and might improve the comfort of children with mechanical ventilation. Further studies are needed to provide conclusive evidence in confirming the effectiveness of music interventions comforting critically ill children in PICUs.

We theoretically investigate the entanglement between two macroscopic rotating mirrors in a Laguerre-Gaussian (L-G) cavity, in which they exchange orbital angular momentum with a same L-G cavity mode, and we examine the influence of various factors such as angular frequencies of two mirrors, effective detuning, temperature and orbital angular momentum of L-G cavity mode on the entanglement. The results show that in some range of mirrors' angular frequencies the entanglement will appear and has strong robustness. And we also study the range of effective detuning and the minimum orbital angular momentum of the L-G cavity mode required to generate entanglement.

Objective: Nuclear β-catenin, a hallmark of active canonical Wnt signaling, can be histologically detected in a subset of cells and cell clusters in up to 94% of adamantinomatous craniopharyngioma (ACP) samples. However, it is unclear whether nuclear β-catenin-containing cells within human ACPs possess the characteristics of tumor stem cells, and it is unknown what role these cells have in ACP., Methods: Primary ACP cells were cultured from 12 human ACP samples. Adamantinomatous CP stem cell-like cells (CSLCs) showing CD44 positivity were isolated from the cultured primary ACP cells by performing magnetic-activated cell sorting. The tumor sphere formation, cell cycle distribution, stemness marker expression, and multidifferentiation potential of the CD44- cells and the CSLCs were analyzed., Results: Compared with the CD44- cells, the cultured human CSLCs formed tumor spheres and expressed CD44 and CD133; moreover, these cells demonstrated nuclear translocation of β-catenin. In addition, the CSLCs demonstrated osteogenic and adipogenic differentiation capacities compared with the CD44- cells. The CSLCs also displayed the capacity for tumor initiation in human-mouse xenografts., Conclusions: These results indicate that CSLCs play an important role in ACP development, calcification, and cystic degeneration.

Large-scale meta-analyses of genome-wide association studies have identified that polymorphisms ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 to be the risk loci for Parkinson's disease (PD) in a Caucasian population. However, the role of these three polymorphisms in a Han Chinese population from mainland China still remains to be clarified. We conducted a large sample study to examine genetic associations of rs6430538, rs199347 and rs14235 with PD in a Han Chinese population of 989 sporadic PD patients and 1058 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. In addition, we conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, no significant differences were found in genotype and allele frequency distribution between PD patients and controls for the three loci, even after being stratified by age at onset. Moreover, we demonstrated that minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our study is the first to demonstrate that ACMSD/TMEM163 rs6430538, GPNMB rs199347 and BCKDK /STX1B rs14235 do not confer a significant risk for sporadic PD in mainland China. Therefore, more replication studies in additional Chinese population and other cohorts and functional studies are warranted to further clarify the role of the three loci in PD susceptibility., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A dynamic guest-binding study of BODIPY-derivative 3 (3 = 1,3,5,7,8-pentamethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) with two Cp*Rh III -based organometallic cages [Cp* 6 Rh 6 (μ-CA) 3 (tpt) 2 ](OTf) 6 1 (H 2 CA = chloranilic acid, tpt = 2,4,6-tripyridyl-1,3,5-triazine) and [Cp* 6 Rh 6 (μ-DHNA) 3 (tpt) 2 ](OTf) 6 2 (H 2 DHNA = 6,11-dihydroxynaphthacene-5,12-dione) have been demonstrated. While guest 3 displays a strong green fluorescence emission, the host-guest complexes 3⊂1 and 3⊂2 exhibit almost no emission. However, fluorescence emission can be again 'turned on' by adding coronene (4) or pyrene (5) into the solution of 3⊂1 and 3⊂2. Guests 4 and 5 show stronger binding affinities toward the organometallic cages 1 and 2 due to the strong electrostatic interactions between the electron-rich guest and electron-deficient tpt resulting in the displacement of 3 by 4 or 5, which eventually helps the fluorescence enhancement. Further guest-binding studies using a Job's plot experiment illustrate the formation of discrete 1 : 1 host-guest complexes which are also supported by 1 H NMR spectroscopy and ESI mass spectrometry. The anion-exchange study with sodium chloride reveals that the chloride ion can effectively disassemble the host frameworks of 1 and 2 releasing the fluorescent guest 3 which can be again encapsulated into the cavity of reassembled cages promoted by the addition of silver triflate.

Alginate oligosaccharides (AOS) showed various biological activities. Traditional protocol for producing AOS was a multiple-step and high-pollution procedure. In this study, a rapid and efficient AOS producing method was developed directly from Laminaria japonica. Natural sun-dried L. japonica with a feed ratio of 1:7 (w/v) was pretreated using cellulase with a dry weight of 3%, for releasing the fermentable sugars (8.5 g/L glucose and 15.2 g/L mannitol). Then, the engineered yeast Yarrowia lipolytica strain with alginate lyase activity was grown using an algae-based medium. After fermentation for 72 h, glucose and mannitol were completely consumed, and 71.8 mM AOS was extracted from the fermentation supernatant. The degree of polymerization (DP) was ranging from 2 to 3. The recovery yield of AOS was about 91.7%. The purity of the extracted AOS was 92.6%. Overall, our work provided new insights for the development of green biotechnologies for oligosaccharide production from seaweed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to investigate the difference of efficacy between conventional moxibustion (CM) and smoke-free moxibustion (SM) for patients with osteoarthritis of the knee (KOA)., Methods: This is a multicentre, randomized, single blinded, parallel-group clinical trial. Patients with KOA were randomly allocated to CM group (69) and SM group (69) in 7 hospitals of China. Moxibustion treatment in 12 sessions over 4 weeks was administrated at 3 acupuncture points (EX-LE4, ST35, and ST36). Patients completed standard questionnaires at baseline and after 2 weeks, 4 weeks, 8 weeks, and 12 weeks. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. The secondary outcomes include Visual Analogue Scale (VAS) and Patient Global Assessment score (PGA)., Results: Analyses showed that the WOMAC score improved in pain (95% CI,-0.1[-1.2 to 0.9], p=0.76), stiffness (95% CI,-0.1 [-0.5 to 0.3], p=0.71), and function (95% CI, 2.2 [-1.3 to 5.8], p=0.22) compared between the two groups at 4 weeks, as well as the VAS score (95% CI,0.1 [-0.3 to 0.6], p=0.60). Similar results presented at 8 and 12 weeks. No statistically significant difference was observed between CM and SM groups for outcome measurements., Conclusions: It suggested that smoke generated during moxibustion treatment does not affect the efficacy of moxibustion in the treatment of KOA, which should be taken into account to be removed for the sake of reducing environmental pollution or moxa smoke exposure of acupuncturists or patients. This trial is registered with Clinical Trials.gov, NCT02772055.

Secreted frizzled‑related protein 1 (sFRP1) is an inhibitor of canonical Wnt signaling; however, previous studies have determined a tumor‑promoting function of sFRP1 in a number of different cancer types. A previous study demonstrated that sFRP1 overexpression was associated with an aggressive phenotype and the activation of transforming growth factor β (TGFβ) signaling. sFRP1 overexpression and sFRP1 knockdown cell models were established. Immunoblotting was conducted to examine the protein levels of the associated molecules. Immunofluorescence staining followed by confocal microscopy was performed to visualize the cytoskeleton alterations and subcellular localization of key proteins. sFRP1 overexpression restored glycogen synthase kinase 3β (GSK3β) activity, which activated Rac family small GTPase 1 (Rac1). GSK3β and Rac1 mediated the effect of sFRP1 on the positive regulation of cell growth and migration/invasion. Inhibition of GSK3β or Rac1 abolished the regulation of sFRP1 on TGFβ/SMAD family member 3 (Smad3) signaling and the aggressive phenotype; however, GSK3β or Rac1 overexpression increased cell migration/invasion and restrained Smad3 activity by preventing its nuclear translocation and limiting its transcriptional activity. The present study demonstrated a tumor‑promoting function of sFRP1‑overexpression by selectively activating TGFβ signaling in gastric cancer cells. GSK3β and Rac1 serve an important function in mediating the sFRP1‑induced malignant alterations and signaling changes.

The Pacific white shrimp ( Litopenaeus vannamei ), one of the most widely cultured shrimp species in the world, often suffers from cold stress. To understand the molecular mechanism of cold tolerance in Pacific white shrimp, we conducted a proteomic analysis on two contrasting shrimp cultivars, namely, cold-tolerant Guihai2 (GH2) and cold-sensitive Guihai1 (GH1), under normal temperature (28°C), under cold stress (16°C), and during recovery to 28°C. In total, 3,349 proteins were identified, among which 2,736 proteins were quantified. Based on gene ontology annotations, differentially expressed proteins largely belonged to biological processes, cellular components, and molecular functions. KEGG pathway annotations indicated that the main changes were observed in the lysosome, ribosomes, and oxidative phosphorylation. Subcellular localization analysis showed a significant increase in proteins present in cytosol, extracellular regions, and mitochondria. Combining enrichment-based clustering analysis and qRT-PCR analysis, we found that glutathione S-transferase, zinc proteinase, m7GpppX diphosphatase, AP2 transcription complex, and zinc-finger transcription factors played a major role in the cold stress response in Pacific white shrimp. Moreover, structure proteins, including different types of lectin and DAPPUDRAFT, were indispensable for cold stress tolerance of the Pacific white shrimp. Results indicate the molecular mechanisms of the Pacific white shrimp in response to cold stress and provide new insight into breeding new cultivars with increased cold tolerance.

The aim of this study was to clarify pathological and anatomical relationships between adamantinomatous craniopharyngiomas (ACP) and their surrounding structures. We previously established a QST classification scheme based on the apparent anatomic origin of the tumors. According to this classification, 13 type Q tumors, 6 type S tumors, and 42 type T ACPs were analyzed. Type Q tumors, which are most likely to involve the pituitary gland, did not invade the area of contact with the adenohypophysis. Instead, tumor invasion was observed in areas where the tumor contacted the neurohypophysis. Type S tumors primarily involved the pituitary stalk; the arachnoid remained present between these tumors and normal structures. Type T tumors were located beneath the basal arachnoid membrane and outside the pia mater. The pia mater was disrupted and finger-like invasions were found in the neural layer of the third ventricle floor along the invasive front. Tumors were never observed to break through the ependymal layer of the third ventricle. The QST classification has important implications for understanding the growth pattern of tumors and can be used to guide surgical procedures.

Background: Due to higher technical requirements, laparoscopic major hepatectomy (LMH) for primary hepatolithiasis have been limited to a few institutions. This retrospective study was performed to evaluate the therapeutic safety, and perioperative and long-term outcomes of LMH versus open major hepatectomy (OMH) for hepatolithiasis., Methods: From January 2012 to December 2016, 61 patients with hepatolithiasis who underwent major hepatectomy were enrolled, including 29 LMH and 32 OMH. The perioperative outcomes and postoperative complications, as well as long-term outcomes, including the stone clearance and recurrence rate, were evaluated., Results: There was no difference of surgical procedures between the two groups. The mean operation time was (262 ± 83) min in the LMH group and (214 ± 66) min in the OMH group (p = 0.05). There is no difference of intra-operative bleeding (310 ± 233) ml versus (421 ± 359) ml (p = 0.05). In the LMH group, there were shorter time to postoperative oral intake ((1.1 ± 0.6) days versus (3.1 ± 1.8) days, p = 0.01) and shorter hospital stay [(7.2 ± 2.3) days versus (11.8 ± 5.5) days, p = 0.03] than the open group. The LMH group had comparable stone clearance rate with the OMH group during the initial surgery (82.8% vs. 84.4%, p = 0.86)., Conclusions: LMH could be an effective and safe treatment for selected patients with hepatolithiasis, with an advantage over OMH in the field of less intra-operative blood loss, less intra-operative transfusion, less overall complications, and faster postoperative recovery.

In this Letter, a compact spectrometer based on upconversion and downconversion luminescence for operation in the infrared, visible, and ultraviolet bands is presented. The proposed spectrometer has three components that are used for dispersion, frequency conversion, and detection. The conversion component converts the incident signal beam into a spectral window appropriate for the detection component. The detection component images the speckle pattern generated by scattering or diffraction in the random structure of the dispersion component. With the two-dimensional intensity data captured from both the speckle pattern and a calibration measurement process, one can reconstruct the spectra of the signal beam by solving a matrix equation. A smoothing simulated annealing algorithm has been implemented to improve the accuracy of the spectral reconstruction. We have analyzed possible sources of error in the algorithm and the corresponding limits of operation. The reported broadband, compact, high-resolution, luminescence-based spectrometer is well suited for portable spectroscopy applications.

Background: Conventional moxibustion is a representative non-drug intervention in traditional Chinese medicine, and it has been reported to produce encouraging results and benefits in relieving symptoms and improving the quality of life for patients with knee osteoarthritis (KOA) in previous clinical trials and systematic reviews. Given that increasing concerns on the safety of generated smoke from conventional moxibustion have received much attention, smoke-free moxibustion is regarded as a potential alternative. However, whether smoke-free moxibustion would display a similar efficacy to that of conventional moxibustion still remains unclear. Therefore, this randomized controlled trial attempts to investigate the difference of efficacy between conventional moxibustion and smoke-free moxibustion in patients with KOA., Methods/design: This is a multicenter, randomized, single-blinded, parallel-group clinical trial. A total of 138 eligible participants with KOA will be randomly allocated to two groups (conventional moxibustion group and smoke-free moxibustion group) in seven hospitals in China. Participants will receive 12 sessions of moxibustion treatment at three acupoints (EX-LE4, ST35, and ST36) over a period of 4 weeks (3 sessions per week). A smoke-removing device is placed at the top of the moxibustion device for the smoke-free moxibustion group (n = 69), while the conventional moxibustion group (n = 69) is treated with traditional moxibustion. The primary outcome measure will be the change of the global scale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) from the baseline to 4 weeks. Secondary outcomes include the visual analog scale VASand Patient Global Assessment scores. Follow-up measurements will be performed on the 8th and 12th weeks after random allocation., Discussion: This study will contribute to providing a solid foundation for the selection of moxibustion in clinical application as well as future research in moxibustion therapy., Trial Registration: ClinicalTrials.gov, NCT02772055 . Registered on 12 May 2016.

Introduction: Knee osteoarthritis is a common form of arthritis in elderly patients that is characterised by pain and functional limitation. Moxibustion has been employed to relieve chronic pain as an alternative therapy for knee osteoarthritis. However, the evidence of its efficacy is equivocal due to the low methodological quality in most clinical studies. Therefore, we are performing a double-blinded, double-placebo, randomised controlled trial to evaluate the efficacy of moxibustion in participants with knee osteoarthritis., Methods and Analysis: This is a multicentre, double-blinded, double-placebo, randomised controlled clinical trial. 144 eligible participants with knee osteoarthritis will be randomly assigned to two different groups in a 1:1 ratio. Participants in the moxibustion group will undergo active moxibustion plus placebo gel, whereas participants in the control group will receive diclofenac sodium gel plus placebo moxibustion. Each participant will receive 12 sessions of active/placebo moxibustion at three acupoints (ST35, ST36 and EX-LE4) as well as 2 months of follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee will be applied three times per day for 4 weeks. The primary outcome measure will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score change at the end of the intervention period from baseline. The secondary outcome measures include changes of other subscales (pain, stiffness and function) of WOMAC, visual analogue scale and patient globalassessment. The safety of moxibustion and diclofenac sodium gel will be assessed at every visit., Ethics and Dissemination: This trial has been approved by the Sichuan Regional Ethics Review Committee (permission number: 2015KL-014). The results of this study are expected to provide clinical evidence on the efficacy of moxibustion for pain relief and physical function improvement in patients with knee osteoarthritis. The findings will be submitted for publication in peer-reviewed medical journals and presented at relevant academic conferences., Trial Registration Number: NCT02769572., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Enumeration of circulating tumor cells (CTCs) is a promising tool in the management of metastatic breast cancer (MBC). This study investigated the capturing efficiency and prognostic value of our previously reported peptide-based nanomagnetic CTC isolation system (Pep@MNPs). We counted CTCs in blood samples taken at baseline (n = 102) and later at patients' first clinical evaluation after starting firstline chemotherapy (n = 72) in a cohort of women treated for MBC. Their median follow-up was 16.3 months (range: 9.0-31.0 months). The CTC detection rate was 69.6 % for the baseline samples. Patients with ≤2 CTC/2 ml at baseline had longer median progression-free survival (PFS) than did those with >2 CTC/2 ml (17.0 months vs. 8.0 months; P = 0.002). Patients with ≤2 CTC/2 ml both at baseline and first clinical evaluation had longest PFS (18.2 months) among all patient groups (P = 0.004). Particularly, among patients with stable disease (SD; per imaging evaluation) our assay could identify those with longer PFS (P < 0.001). Patients with >2 CTC/2 ml at baseline were also significantly more likely to suffer liver metastasis (P = 0.010). This study confirmed the prognostic value of Pep@MNPs assays for MBC patients who undergo firstline chemotherapy, and offered extra stratification regarding PFS for patients with SD, and a possible indicator for patients at risk for liver metastasis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01-1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73-1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89-1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53-3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

Whether a mixed type of craniopharyngioma (CP) exists and whether papillary craniopharyngioma (pCP) is on a histopathological continuum with Rathke's cleft cyst (RCC) remain controversial. Herein, we examined the expression and localization of β-catenin, BRAF p.V600E (V600E), and triggering receptor expressed on myeloid cells-1 (TREM-1) in 58 samples including 20 pCPs, 26 adamantinomatous craniopharyngiomas (aCP), and 12 RCCs. Five aCPs were diagnosed with mixed type CPs and the remaining 21 cases were pure aCPs. Four of the 12 RCCs presented with significant squamous epithelium (SE). V600E immunoreactivity was observed in all pCPs in the cytoplasm, but not in the nuclei. aCPs and RCCs, including mixed type CP, did not express V600E. Nuclear β-catenin translocation was detected exclusively in aCPs. TREM-1 was expressed in pCPs. Additionally, TREM-1 expression was detected in the SE of 5 "mixed type" CPs, while it was absent in pure aCPs. TREM-1 was expressed in 4 RCCs with SE, but not in the remaining 8 RCCs. TREM-1 mRNA levels were compared in cultured pCP and aCP cells. TREM-1 mRNA level was significantly (p < 0.001; up to 4.045 fold) higher in pCPs than in aCPs. Western blotting revealed a significantly (p < 0.001; up to 7.19 fold) lower level of TREM-1 expression in aCP cells compared to that in pCP cells. Our findings further supported that RCC and pCP may represent two ends of a morphological spectrum. A variant showing overlapping histological features of aCP and pCP should not be considered as a mixed type., Competing Interests: The authors declare that they have no conflicts of interest.

OBJECT Craniopharyngiomas are associated with a high rate of recurrence. The surgical management of recurrent lesions has been among the most challenging neurosurgical procedures because of the craniopharyngioma's complex topographical relationship with surrounding structures. The aim of this study was to define the determinative role of the site of origin on the growth pattern and clinical features of recurrent craniopharyngiomas. METHODS The authors performed a retrospective analysis of 52 patients who had undergone uniform treatment by a single surgeon. For each patient, data concerning symptoms and signs, imaging features, hypothalamic-pituitary function, and recurrence-free survival rate were collected. RESULTS For children, delayed puberty was more frequent in the group with Type I (infradiaphragmatic) craniopharyngioma than in the group with Type TS (tuberoinfundibular and suprasellar extraventricular) lesions (p < 0.05). For adults, blindness was more frequent in the Type I group than in the Type TS group (p < 0.05). Nausea or vomiting, delayed puberty, and growth retardation were more frequent in children than in adults (p < 0.05). Overall clinical outcome was good in 48.07% of the patients and poor in 51.92%. Patients with Type TS recurrent tumors had significantly worse functional outcomes and hypothalamic function than patients with the Type I recurrent tumors but better pituitary function especially in children. CONCLUSIONS The origin of recurrent craniopharyngiomas significantly affected the symptoms, signs, functional outcomes, and hypothalamic-pituitary functions of patients undergoing repeated surgery. Differences in tumor growth patterns and site of origin should be considered when one is comparing outcomes and survival across treatment paradigms in patients with recurrent craniopharyngiomas.

Observational studies showed that tooth loss is associated with gastric cancer, but the findings are inconsistent. In this study, a meta-analysis was conducted to evaluate the relationship between tooth loss and gastric cancer. Relevant studies were screened in PubMed and Embase databases, and nine observational studies were considered eligible for the analysis. The combined relative risks for the highest versus the lowest categories of tooth loss were 1.86 (95% CI: 1.08-3.21) and 1.31 (95% CI: 1.12-1.53) in case control and cohort studies, respectively. However, unstable results were observed in the stratified and sensitivity analysis. The current evidence, based solely on four case-control studies and five cohort studies, suggested that tooth loss is a potential marker of gastric cancer. However, we can not concluded at this time that tooth loss may be a risk factor for gastric cancer due to significant heterogeneity among studies and mixed results between case-control studies and cohort studies. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of gastric cancer.

Heavy metal pollution in marine fish has become an important worldwide concern, not only because of the threat to fish in general, but also due to human health risks associated with fish consumption. To investigate the occurrence of heavy metals in marine fish species from the South China Sea, 14 fish species were collected along the coastline of Hainan China during the spring of 2012 and examined for species- and tissue-specific accumulation. The median concentrations of Cd, Cr, Cu, Zn, Pb and As in muscle tissue of the examined fish species were not detectable (ND), 2.02, 0.24, 2.64, 0.025, and 1.13 mg kg(-1) wet weight, respectively. Levels of Cu, Zn, Cd and Cr were found to be higher in the liver and gills than in muscle, while Pb was preferentially accumulated in the gills. Differing from other heavy metals, As did not exhibit tissue-specific accumulation. Inter-species differences of heavy metal accumulation were attributed to the different habitat and diet characteristics of marine fish. Human dietary exposure assessment suggested that the amounts of both Cr and As in marine wild fish collected from the sites around Hainan, China were not compliant with the safety standard of less than 79.2 g d(-1) for wild marine fish set by the Joint FAO/WHO Expert Committee on Food Additives. Further research to identify the explicit sources of Cr and As in marine fish from South China Sea should be established.

Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3) and isoconiochaetone C (4), along with three known remisporine B (1), coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6) were isolated from a mutant from the diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. The structures of 2-4 including the absolute configurations were determined by spectroscopic methods, especially by NMR analysis and electronic circular dichroism (ECD) experiments in conjunction with calculations. The absolute configuration of the known remisporine B (1) was determined for the first time. Compounds 2 and 3 have a rare feature that has only been reported in one example so far. The compounds 1-6 were evaluated for their cytotoxicity against several human cancer cell lines. The present work explored the great potential of our previous DES mutagenesis strategy for activating silent fungal pathways, which has accelerated the discovery of new bioactive compounds.