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Objective: To investigate the clinical, radiological, and pathological features of anaplastic gangliogliomas (AGGs) and to determine whether these tumors represent a distinct entity. Methods: Consecutive 667 cases of ganglioglioma (GG) diagnosed at the Xuanwu Hospital, Capital Medical University, Beijing, China between January 2015 and July 2023 were screened. Among these cases, 9 pathologically confirmed AGG cases were identified. Their clinical, radiological, treatment, and outcome data were analyzed retrospectively. Most of the tumor samples were subject to next-generation sequencing, while a subset of them were subject to DNA methylation profiling. Results: Among the 9 patients, there were five males and four females, with a median age of 8 years. Epileptic seizures (5/9) were the most frequently presented symptom. Radiological examinations showed three types of radiological manifestations: four cases showed abnormal MRI signals with no significant mass effects and mild enhancement; two cases demonstrated a mixed solid-cystic density lesion with peritumoral edema, which showed significant heterogeneous enhancement and obvious mass effects, and one case displayed cystic cavity formation with nodules on MRI, which showed evident enhancements. All cases exhibited mutations that were predicted to activate the MAP kinase signaling pathway, including seven with BRAF p.V600E mutation and two with NF1 mutation. Five AGGs with mutations involving the MAP kinase signaling pathway also had concurrent mutations, including three with CDKN2A homozygous deletion, one with a TERT promoter mutation, one with a H3F3A mutation, and one with a PTEN mutation. Conclusions: AGG exhibits a distinct spectrum of pathology, genetic mutations and clinical behaviors, differing from GG. Given these characteristics suggest that AGG may be a distinct tumor type, further expansion of the case series is needed. Therefore, a comprehensive integration of clinical, histological, and molecular analyses is required to correctly diagnose AGG. It will also help guide treatments and prognostication.

Cancer is associated with the highest mortality rate globally. While life-saving screening and treatments exist, better awareness is needed. RNF187, an E3 ligase regulating biological processes, belongs to the RING domain-containing E3 ligase family. RNF187 may serve as an oncogene due to abnormal expression in tumors. However, its association with immune infiltration and prognosis across various cancers remains unclear. We searched several databases including TCGA, GTE x, CCLE, TIMER, and GSEA. R software was used to evaluate RNF187 differential expression, survival, pathology stage, DNA methylation, tumor mutational burden (TMB), microsatellite instability (MSI), gene co-expression analysis, mismatch repairs (MMRs), tumor microenvironment (TME), and immune cell infiltration. Clinicopathological data were collected, and immunohistochemistry was used to verify RNF187 expression in tumor tissues. RNF187 expression was up-regulated in various cancers compared to that in normal tissues and associated with poor patient outcomes. Dysregulation of RNF187 expression in multiple cancer types was strongly correlated with DNA methylation, MMR, MSI, and TMB. RNF187 could interact with different immune cells in cancers. Biomarkers associated with RNF187 may be helpful for prognosis and immunology in treating pan-cancer patients., (© 2024 John Wiley & Sons Ltd.)

Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising., Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort., Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%-62.84%] at 95.53% [95% CI: 94.62%-96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%-35.07%] at 99.37% [95% CI: 98.91%-99.64%] specificity for US) (P < 0.01, Fisher's exact test). PreCar Score plus US further achieved a higher sensitivity of 60.53% at 95.08% specificity for early/very early HCC screening., Interpretation: Our study developed and validated a cfDNA-based screening tool (PreCar Score) for HCC in cohorts at high risk. The combination of PreCar Score and US can serve as a promising and practical strategy for routine HCC care., Funding: A full list of funding bodies that contributed to this study can be found in Acknowledgments section., Competing Interests: Declaration of interests JB, QZZ, JZ, FMS, YW, and LW are employees of Berry Oncology Corporation. All the authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Modern Bai Jiu(liquor) was called Shao Jiu in ancient times.By consulting ancient books, it was found that there was a distillation and preparation process of Shao Jiu before the Ming Dynasty, but due to its high toxicity, the scope of application was limited, and there were few records of its medicinal use.However many records of its medicinal use was found in the Compendium of Materia Medica («»).By comparing the medical books that recorded Shao Jiu in previous dynasties, it is found that the Compendium of Materia Medica comprehensively records the relevant cognition and application of the medicinal use of Shao Jiu for the first time. The book lists in detail the causes of the toxicity of Shao Jiu and the methods to avoid it, comprehensively expounds its characteristics, efficacy and indications, lists a variety of ways to use it, skillfully uses Shao Jiu to treat syphilis sores, and proposes that high-concentration Shao Jiu can be used as a solvent for medical liquor.The record of Shao Jiu in the Compendium of Materia Medica had a profound impact on the medical liquor of later generations.The use of Shao Jiu in the Qing Dynasty continued to expand, and the types of medicinal liquor were also constantly enriched. The record of Shao Jiu in the Compendium of Materia Medica can also provide a reference for the medicinal use of modern liquor.

Inhibition of plasmid transfer, including transformation and conjugation, is essential to prevent the spread of plasmid-encoded antimicrobial resistance. Photosensitizers have been successfully used in the treatment of serious infectious diseases, however, the effects of photosensitizers on the plasmid transfer are still elusive. In this study, we determined the transformation and conjugation efficiency of plasmid pUC19 and pRP4, respectively, when exposed to a photosensitizer (Visible Light-activated Rose Bengal, VLRB). The results showed that the activation of VLRB resulted in up to a 580-fold decrease in the transformation frequency of pUC19 and a 10-fold decrease in the conjugation frequency of pRP4 compared with the non-VLRB control. The inhibition of pUC19 transformation by VLRB exhibited a dose-dependent manner and was attributed to the changes in the plasmid conformation. The inhibition of pRP4 conjugation was associated with the generation of extracellular free radicals, induced oxidative stress, suppression of the mating pair formation gene (trbBp) and DNA transfer and replication gene (trfAp), and enhanced expression of the global regulatory genes (korA, korB, and trbA). These findings highlight the potential of visible light-activated photosensitizer for mitigating the dissemination of plasmid-encoded antibiotic resistance genes., 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.)

Objective: To evaluate the immunogenicity and protective effect of a multicomponent recombinant protein vaccine EPRHP014 constructed independently and provide a scientific basis for developing new tuberculosis (TB) vaccine and effective prevention and control of TB. Methods: Three full-length Mycobacterium ( M. ) tuberculosis protein antigens (EsxH, Rv2628, and HspX) and two epitope-predicted and optimized epitope-dominant protein antigens (nPPE18 and nPstS1) were selected, from which five protein antigens were used to construct a protein antigen composition EPRHP014, including a fusion expression multi-component protein antigen (EPRHP014f) and a multi-component mixed protein antigen (EPRHP014m) formed with the five single protein using clone, purification, and purification respectively. Multicomponent protein vaccines EPRHP014f and EPRHP014m were prepared with aluminum adjuvant, and the BCG vaccine was used as a control. ELISA detected the titer of serum-specific antibodies, the secretion of various cytokines was detected by ELISpot and Luminex, and immune protection was observed by the M. tuberculosis growth inhibition test in vitro. The results were statistically analyzed by t -test or rank sum test, and P <0.05 was considered a statistically significant difference. Results: Mice Immunized with EPRHP014m and EPRHP014f could produce highly effective IgG antibodies and their subtypes IgG1 and IgG2a, and the antibody titers were similar to those of mice immunized with BCG, with no statistical significance ( P >0.05). The number of spot-forming cells (SFC) secreting IFN-γ and IL-4 induced by EPRHP014f group was significantly higher than those by EPRHP014m group and BCG group ( P <0.05), but there was no significant difference in the number of SFC for IFN-γ and IL-4 induced between EPRHP014m group and BCG group ( P >0.05). The secretion levels of GM-CSF and IL-12p70 induced by the EPRHP014m group were higher than those of the BCG group ( P <0.05), but there was no significant difference in the levels of IL-6 and IL-10 induced between EPRHP014m group and BCG group ( P >0.05). There was no significant difference in the secretions of IL-6, IL-10, IL-12, and GM-CSF between the EPRHP014f and BCG groups ( P >0.05). EPRHP014m group, EPRHP014f group, and BCG group had obvious antibacterial effects in vitro, and the difference was insignificant ( P >0.05). Conclusion: Both EPRHP014f and EPRHP014m can induce strong humoral and cellular immune responses in mice after immunization, and have a strong ability to inhibit the growth of M. tuberculosis in vitro, indicating that the antigen composition EPRHP014 has good potential in the development and application of TB vaccine.

Background: Neurofilament light chain (NfL) is a novel biomarker for the assessment of neurological function after cardiac arrest (CA). Although meta-analysis has confirmed its predictive value, it has not conducted a more detailed analysis of its research. We conducted a meta-analysis to evaluate the relationship between serum NfL level and neurological prognosis in patients with spontaneous circulation recovery after CA, and subgroup analysis was conducted according to sample collection time, time to assess neurological function, study design, whether TTM was received, the method of specimen determination, and the presence of neurological disease in patients. To analyze the influence of these factors on the predictive value of serum NfL., Methods: Published Cochrane reviews and an updated, extended search of MEDLINE, Cochrane Library, Embase, Scopus, ClinicalKey, CINAHL, and Web of Science for relevant studies until March 2022 were assessed through inclusion and exclusion criteria. The standard mean difference and 95% confidence interval were calculated using the random-effects model or fixed-effects model to assess the association between one variable factor NfL level and the outcome of CA patients. Subgroup analysis according to sample collection time was performed. The prognosis analysis and publication bias were also assessed using Egger's and Begg's tests., Results: Among 1209 related articles for screening, 6 studies (1360 patients) met the inclusion criteria and were selected for meta-analysis. The level of serum NfL in the good prognosis group (CPC1-2, CPC: cerebral performance category score) was significantly lower than that in the poor prognosis group (CPC3-5)SMD(standardized mean difference) = 0.553, 95%CI(confidence interval) = 0.418-0.687, I2 = 65.5% P<0.05). And this relationship also exists at each sampling time point (NfL specimens were collected on admission: SMD:0.48,95%CI:0.24-0.73; Samples were collected 24 hours after CA: SMD:0.60,95%CI:0.32-0.88;Specimens were obtained 48 hours after CA: SMD:0.51, 95%CI:0.18-0.85;Specimens were obtained 72 hours after CA: SMD:0.59, 95%CI:0.38-0.81)., Conclusion: NfL may play a potential neuroprognostication role in postcardiac arrest patients with spontaneous circulation, regardless of when the sample was collected after CA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sixteen patients with recurrent high-grade glioma who were treated by domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the Neurosurgery Department of Xuanwu Hospital of Capital Medical University from 1st January 2021 to 31st December 2021 were prospectively included, with 11 males and 5 females, and aged 27-74 (50±16) years. The duration of surgery, the rate of ablation after surgery, and perioperative complications were assessed. The patients were followed up every 3 months to assess survival and progression. A total of 5 WHO grade Ⅲ patients and 11 WHO grade Ⅳ patients were included. The operation time was 144 (109, 176) min, 28 targeted lesions were detected, and the ablation rate [ M ( Q 1 , Q 3 )] was 91.0% (87.4%, 93.3%). After surgery, 2 patients (2/16) had decreased limb muscle strength, and no perioperative death or other serious complications occurred. The median time to a complete response was 12 (5, 14) months in WHO Grade Ⅲ patients, and one died 12 months after surgery, while the median time to a complete response was 3 (1, 8) months in 11 WHO Grade Ⅳ patients, with a total of 8 deaths at the last follow-up. Therefore, domestic MRgLITT has certain efficacy and safety in the treatment of recurrent high-grade glioma, providing a new option for patients with recurrent glioma.

Background: The incidence, risk factors, and pathogenesis of early neurological deterioration (END) in posterior circulation stroke are still unclear. In this study, we aimed to determine the risk factors and prognosis of END in patients with acute posterior circulation cerebral infarction., Methods: Acute posterior circulation ischemic stroke patients who had completed neuroimaging within 72 h of onset were selected from a prospective registry study Demographic characteristics, physiological data, medical history, laboratory data, in-hospital evaluation, neurological severity and TOAST classification, treatment, and the modified Rankin Scale (mRS) score of patients were assessed. Early neurological deterioration was defined as an increase of 2 points in the National Institutes of Health Stroke Scale score between the baseline and 72 h evaluation. Favorable and poor outcomes were defined as mRSs of 02 and≥ 3, respectively, at 3 months. The incidence and risk factors were evaluated by univariate and multivariate regression analysis (step-back method)., Results: The analysis included 455 subjects with an acute posterior circulation non-cardiac ischemic stroke, 330 (72.53 %) of them male, with an average age of 63.12 ( ± 10.14) years and with 47 (10.33 %) having END. The results of univariate and multivariate logistic regression analysis showed that BATMAN scores ≥ 5 (OR: 0.1, 95 % CI: 0.02-0.53, P < 0.01), large artery atherosclerosis (OR: 11.55, 95 % CI: 4.18-31.93, P < 0.01), vascular stenosis > 50 % (OR: 2.44, 95 % CI: 1.1-5.42, P = 0.029), reperfusion therapy (OR: 4.21, 95 % CI: 1.66-10.64, P < 0.01), and the distribution of pontine lesions (OR: 5.66, 95 % CI: 2.39-13.44, P < 0.01) were significantly associated with END. Patients with END had a lower rate of favorable outcomes at discharge and long-term follow-up (P < 0.001), regardless of whether they received reperfusion therapy., Conclusion: The lesion distribution of the pons, the progression of temporo-occipital lobe lesions, and large arterial atherosclerosis are independent risk factors of END that might predict a poor short- and long-term prognosis., Competing Interests: Conflict of Interest Statement There are no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The North China Medical College typically represented medical colleges for traditional Chinese medicine in the 1930s when many of them were set up. It was based on the principles of centring on traditional Chinese medicine, following western medicine and integrated medicine in teaching. This led to the emergence of a great number of people with a high level of traditional Chinese medicine and strong belief in it. In terms of the textbooks and handouts for western medicine, compared to similar textbooks in other medical colleges, such as the Medical College of Xie He, at that time, the textbooks in the North China Medical College covered a variety of perspectives and categories. It was found that 20 textbooks for western medicine in the North China Medical College were designed reasonably in content and were simple and applicable in teaching. More importantly, it contained some traditional Chinese medicine in different degrees, with its typical characteristics. The course design and textbook compilation provided references for the teaching in contemporary medical universities.

Nitrate-reducing iron(II) oxidation (NRFO) has been intensively reported in various bacteria. Iron(II) oxidation is found to be involved in both enzymatic and chemical reactions in nitrate-reducing Fe(II)-oxidizing microorganisms (NRFOMs). However, little is known about the relative contribution of biotic and abiotic reactions to iron(II) oxidation for the common nitrate reducers during the NRFO process. In this study, the typical nitrate reducers, four Enterobacter strains E. hormaechei , E. tabaci , E. mori and E. asburiae , were utilized as the model microorganisms. The comparison of the kinetics of nitrate, iron(II) and nitrite and N 2 O production in setups with and without iron(II) indicates a mixture of enzymatic and abiotic oxidation of iron(II) in all four Enterobacter strains. It was estimated that 22-29% of total oxidized iron(II) was coupled to microbial nitrate reduction by E. hormaechei , E. tabaci , E. mori , and E. asburiae . Enterobacter strains displayed an metabolic inactivity with heavy iron(III) encrustation on the cell surface in the NRFOmedium during days of incubation. Moreover, both respiratory and periplasmic nitrate-reducing genes are encoded by genomes of Enterobacter strains, suggesting that cell encrustation may occur with periplasmic iron(III) oxide precipitation as well as the surface iron(II) mineral coating for nitrate reducers. Overall, this study clarified the potential role of nitrate reducers in the biochemical cycling of iron under anoxic conditions, in turn, re-shaping their activity during denitrification because of cell encrustation with iron(III) minerals.

(1) Background: Accurate localization of the epileptogenic zone and understanding the related functional connectivity (FC) alterations are critical for the prediction of clinical prognosis in patients with temporal lobe epilepsy (TLE). We aim to localize the hypometabolic region in TLE patients, compare the differences in FC alterations based on hypometabolic region and structural lesion, respectively, and explore their relationships with clinical prognosis. (2) Methods: Thirty-two TLE patients and 26 controls were recruited. Patients underwent 18F-FDG PET/MR scan, surgical treatment, and a 2−3-year follow-up. Visual assessment and voxel-wise analyses were performed to identify hypometabolic regions. ROI-based FC analyses were performed. Relationships between clinical prognosis and FC values were performed by using Pearson correlation analyses and receiver operating characteristic (ROC) analysis. (3) Results: Hypometabolic regions in TLE patients were found in the ipsilateral hippocampus, parahippocampal gyrus, and temporal lobe (p < 0.001). Functional alterations based on hypometabolic regions showed a more extensive whole-brain FC reduction. FC values of these regions negatively correlated with epilepsy duration (p < 0.05), and the ROC curve of them showed significant accuracy in predicting postsurgical outcome. (4) Conclusions: In TLE patients, FC related with hypometabolic region obtained by PET/fMRI may provide value in the prediction of disease progression and seizure-free outcome.

Plasmid conjugation contributes greatly to the spread of antibiotic resistance genes (ARGs) in soils. However, the spread potential in the gut of soil fauna remains poorly studied, and little was known about the impact of host age on ARGs dissemination in the gut microbiota of soil animals. Here, the typical nematode-Caenorhabditis elegans was employed as the model soil animal, aiming to investigate transfer of broad-host-range IncP-1ɛ from Escherichia coli MG1655 to gut microbiota within 6 days under varied temperature gradients (15, 20 and 25 °C) using qPCR combined with plate screening. Results showed that conjugation rates increased with incubation time and rising temperature in the gut of C. elegans, sharing a similar trend with abundances of plasmid conjugation relevant genes such as trbBp (mating pair formation) and trfAp (plasmid replication). Incubation time and temperature significantly shaped the gut microbial community of C. elegans. Core microbiota in the gut of C. elegans, including Enterobacteriaceae, Lactobacillaceae and Leuconostocaceae, constituted a large part of transconjugal pool for plasmid IncP-1ɛ. Our results highlight an important sink of gut microbiota for ARGs dissemination and upregulation of ARGs transfer in the gut microbiota with host age, further potentially stimulating evolution of ARGs in terrestrial environments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The connotation of theory of "synchronization of heaven- qi , earth- qi and human- qi " in Zhuang Medicine is introduced, and its association with human physiological state, pathological changes and acupuncture treatment mechanism are discussed. The main points, acupuncture manipulation and clinical acupoint selection of acupuncture and moxibustion of Zhuang Medicine are guided by this theory. The points are mainly composed of Huan points, Luoyang points and experience-based points, which are divided into heaven part, earth part and human part according to the positions in the human body. The acupuncture manipulation is divided into mild manipulation, moderate manipulation and heavy manipulation according to heaven, earth and human theory. With the point prescriptions for headache, dysmenorrhea and herpes zoster sore as examples, the application of this theory in the clinical acupoint selection is explained.

The objective of this study was to identify the decussating dentato-rubro-thalamic tract (d-DRTT) and its afferent and efferent connections in healthy humans using diffusion spectrum imaging (DSI) techniques. In the present study, the trajectory and lateralization of the d-DRTT was explored using data from subjects in the Massachusetts General Hospital-Human Connectome Project adult diffusion dataset. The afferent and efferent networks that compose the cerebello-thalamo-cerebral pathways were also reconstructed. Correlation analysis was performed to identify interrelationships between subdivisions of the cerebello-dentato-rubro-thalamic and thalamo-cerebral connections. The d-DRTT was visualized bilaterally in 28 subjects. According to a normalized quantitative anisotropy and lateralization index evaluation, the left and right d-DRTT were relatively symmetric. Afferent regions were found mainly in the posterior cerebellum, especially the entire lobule VII (crus I, II and VIIb). Efferent fibers mainly are projected to the contralateral frontal cortex, including the motor and nonmotor regions. Correlations between cerebello-thalamic connections and thalamo-cerebral connections were positive, including the lobule VIIa (crus I and II) to the medial prefrontal cortex (MPFC) and the dorsolateral prefrontal cortex and lobules VI, VIIb, VIII, and IX, to the MPFC and motor and premotor areas. These results provide DSI-based tratographic evidence showing segregated and parallel cerebellar outputs to cerebral regions. The posterior cerebellum may play an important role in supporting and handling cognitive activities through d-DRTT. Future studies will allow for a more comprehensive understanding of cerebello-cerebral connections., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Compound kushen injection (CKI), a Chinese patent drug, is widely used in the treatment of various cancers, especially neoplasms of the digestive system. However, the underlying mechanism of CKI in pancreatic cancer (PC) treatment has not been totally elucidated., Methods: Here, to overcome the limitation of conventional network pharmacology methods with a weak combination with clinical information, this study proposes a network pharmacology approach of integrated bioinformatics that applies a weighted gene co-expression network analysis (WGCNA) to conventional network pharmacology, and then integrates molecular docking technology and biological experiments to verify the results of this network pharmacology analysis., Results: The WGCNA analysis revealed 2 gene modules closely associated with classification, staging and survival status of PC. Further CytoHubba analysis revealed 10 hub genes (NCAPG, BUB1, CDK1, TPX2, DLGAP5, INAVA, MST1R, TMPRSS4, TMEM92 and SFN) associated with the development of PC, and survival analysis found 5 genes (TSPOAP1, ADGRG6, GPR87, FAM111B and MMP28) associated with the prognosis and survival of PC. By integrating these results into the conventional network pharmacology study of CKI treating PC, we found that the mechanism of CKI for PC treatment was related to cell cycle, JAK-STAT, ErbB, PI3K-Akt and mTOR signalling pathways. Finally, we found that CDK1, JAK1, EGFR, MAPK1 and MAPK3 served as core genes regulated by CKI in PC treatment, and were further verified by molecular docking, cell proliferation assay, RT-qPCR and western blot analysis., Conclusions: Overall, this study suggests that the optimized network pharmacology approach is suitable to explore the molecular mechanism of CKI in the treatment of PC, which provides a reference for further investigating biomarkers for diagnosis and prognosis of PC and even the clinical rational application of CKI., (© 2021. The Author(s).)

Objective: To investigate the safety and efficacy of stereotactic-EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) with three-dimensional lesioning in the treatment of drug-resistant insular epilepsy. Methods: Seven patients with drug-resistant insular epilepsy who underwent SEEG-guided RF-TC with three-dimensional ablation at the Department of Neurosurgery of Xuanwu Hospital, Capital Medical University from February 2017 to June 2019 were retrospectively enrolled. Presurgical evaluation including semiology, EEG and imaging results suggested that the epileptogenic zone was located in the insular lobe. All patients underwent SEEG recording and three-dimensional RF-TC. Postoperative follow-up was conducted by outpatient visits or telephone, the clinical efficacy was evaluated based on Engel classification and the relevant complications were documented. Results: Seven patients were followed up at 18 months after surgery. Among them, 4 were seizure free (Engel ⅠA), 2 had nondisabling simple partial seizures (Engel ⅠB) and 1 achieved 75% decrease (Engel ⅢA) in seizure frequency. Postoperative complications occurred in 3 patients which included decreased sensation in the right lower extremity, decreased strength in the right upper extremity, glossolalia, decline in memory and comprehension. No permanent neurological dysfunction was detected. Conclusion: SEEG-guided RF-TC with three-dimensional lesioning is minimally invasive, safe and effective in the treatment of drug-resistant insular epilepsy and can serve as a complementary method for resection surgery.

Objective: To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Methods: Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. Results: A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class Ⅰ cases (59.1%), 2 Engel class Ⅱ cases (9.1%), 2 Engel class Ⅲ cases (9.1%) and 5 Engel class Ⅳ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Conclusion: Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.

Objectives: To evaluate the immunogenicity of Mycobacterium intracellulare proteins and determine the cross-reactive proteins between M. intracellulare and M. tuberculosis., Methods: Protein extracts from M. intracellulare were used to immunize BALB/c mice. The antigens were evaluated using cellular and humoral immunoassays. The common genes between M. intracellular and M. tuberculosis were identified using genome-wide comparative analysis, and cross-reactive proteins were screened using immunoproteome microarrays., Results: Immunization with M. intracellulare proteins induced significantly higher levels of the cytokines interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-12 (IL-12), interleukin-6 (IL-6) and immunoglobulins IgG, IgG1, IgM, and IgG2a in mouse serum. Bone marrow-derived macrophages isolated from mice immunized with M. intracellulare antigens displayed significantly lower bacillary loads than those isolated from mice immunized with adjuvants. Whole-genome sequence analysis revealed 396 common genes between M. intracellulare and M. tuberculosis . Microchip hybridization with M. tuberculosis proteins revealed the presence of 478 proteins in the serum of mice immunized with M. intracellulare protein extracts. Sixty common antigens were found using both microchip and genomic comparative analyses., Conclusion: This is the advanced study to investigate the immunogenicity of M. intracellulare proteins and the cross-reactive proteins between M. intracellulare and M. tuberculosis . The results revealed the presence of a number of cross-reactive proteins between M. intracellulare and M. tuberculosis . Therefore, this study provides a new way of identifying immunogenic proteins for use in tuberculosis vaccines against both M. intracellulare and M. tuberculosis in future., (Copyright © 2021 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Conjunctive transfer of antibiotic resistance genes (ARGs) among bacteria driven by plasmids facilitated the evolution and spread of antibiotic resistance. Heavy metal exposure accelerated the plasmid-mediated conjunctive transfer of ARGs. Nanomaterials are well-known adsorbents for heavy metals removal, with the capability of combatting resistant bacteria/facilitating conjunctive transfer of ARGs. However, co-effect of heavy metals and nanomaterials on plasmid-mediated conjunctive transfer of ARGs was still unknown. In this study, we investigated the effect of the simultaneous exposure of Cd 2+ and nano Fe 2 O 3 on conjugative transfer of plasmid RP4 from Pseudomonas putida KT2442 to water microbial community. The permeability of bacterial cell membranes, antioxidant enzyme activities and conjugation gene expression were also investigated. The results suggested that the combination of Cd 2+ and high concentration nano Fe 2 O 3 (10 mg/L and 100 mg/L) significantly increased conjugative transfer frequencies of RP4 plasmid (p < 0.05). The most transconjugants were detected in the treatment of co-exposure to Cd 2+ and nano Fe 2 O 3 , the majority of which were identified to be human pathogens. The mechanisms of the exacerbated conjugative transfer of ARGs were involved in the enhancement of cell membrane permeability, antioxidant enzyme activities, and mRNA expression levels of the conjugation genes by the co-effect of Cd 2+ and nano Fe 2 O 3 . This study confirmed that the simultaneous exposure to Cd 2+ and nano Fe 2 O 3 exerted a synergetic co-effect on plasmid-mediated conjunctive transfer of ARGs, emphasizing that the co-effect of nanomaterials and heavy metals should be prudently evaluated when combating antibiotic resistance., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear., Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC ( n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study., Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone., Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation., (©2021 American Association for Cancer Research.)

Introduction: In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE., Methods and Analysis: STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes., Discussion: SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE., Trial Registration: ClinicalTrials.gov NCT03941613 . Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

Background: Risk stratification of patients with acute myocardial infarction (AMI) is of great clinical significance., Hypothesis: The present study aimed to establish an optimized risk score to predict short-term (6-month) death among rural AMI patients from China., Methods: We enrolled 6581 AMI patients and extracted relevant data. Patients were divided chronologically into a derivation cohort (n = 5539), to establish the multivariable risk prediction model, and a validation cohort (n = 1042), to validate the risk score., Results: Six variables were identified as independent predictors of short-term death and were used to establish the risk score: age, Killip class, blood glucose, creatinine, pulmonary artery systolic pressure, and percutaneous coronary intervention treatment. The area under the ROC curve (AUC) of the optimized risk score was 0.82 within the derivation cohort and 0.81 within the validation cohort. The diagnostic performance of the optimized risk score was superior to that of the GRACE risk score (AUC 0.76 and 0.75 in the derivation and validation cohorts, respectively; p < .05)., Conclusion: These results indicate that the optimized scoring method developed here is a simple and valuable instrument to accurately predict the risk of short-term mortality in rural patients with AMI., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Conflicts in regarding the lateralization of the seizure onset for mesial temporal lobe epilepsy (MTLE) are frequently encountered during presurgical evaluation. As a more elaborate, quantified protocol, indices of diffusion spectrum imaging (DSI) might be sensitive to evaluate the seizure involvement. However, the accuracy was less revealed. Herein, we determined the lateralizing value of the DSI indices among MTLE patients., Methods: Eleven MTLE patients were enrolled together with 11 matched health contrasts. All the participants underwent a DSI scan and with reconstruction of the diffusion scalar, including quantitative anisotropy (QA), isotropic (ISO), and track density imaging (TDI) values. Statistics of these indices were applied to identify the differences between the healthy and ipsilateral sides, and those between the patients and the controls, with special attention to areas of the crura of fornix (FORX), the parahippocampal radiation of the cingulum (PHCR), the hippocampus (HP), parahippocampus (PHC), amygdala (AM) and entorhinal cortex (EC)., Results: Regarding lateralization, TDI of the FORX and the PHCR reached an AUC value of 0.95 and 0.93, respectively (P<0.05), and QA, ISO, TDI of the PHCR, as well as TDI of the FORX were statistically significant amongst the laterals of the patients (P<0.05). Also, the QA of the PHCR were statistically different in the patients' ipsilateral side relative to the contrasts (P<0.017). The diffusion level on different grey matter structures were significantly decreased including HP, AM and EC in GQI space (P<0.017)., Conclusions: The quantitative diffusion scalars of the DSI, especially TDI of the FORX and the PHCR, are sensitive indices to define the ipsilateral side for MTLE patients. For preliminary exploration, the use of quantitative DSI scalars may help to improve the seizure outcome by increasing the accuracy of localization and lateralization for MTLE., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5719). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Purpose: There are few studies on the glucose metabolic characteristics of the extra-hypothalamic cortex in the hypothalamic hamartomas (HH). A comprehensive understanding of pathogenic progression of the disease is required from the perspective of cortical metabolism; therefore, we aimed to characterize metabolic characteristics of extra-hypothalamic in HH patients. Methods: We investigated the metabolic characteristics of 16 HH patients, all of whom underwent epilepsy evaluation at Xuan Wu Hospital between 2017 and 2019. The lateralization and cortical distribution pattern of hypometabolism was assessed and related to HH mass neuroanatomy on magnetic resonance imaging (MRI) as well as scalp-electroencephalogram (scalp-EEG) abnormalities. Furthermore, asymmetry measurements of region of interest (ROI) in the temporal cortex (hippocampal formation, amygdala, and lateral temporal neocortex) were quantitatively assessed based on the normalized average positron emission tomography (PET) voxel values. The surgery prognosis was assessed using the International League Against Epilepsy (ILAE) classification system. Results: The lateralization of hypometabolism in global visual ratings was consistent with the HH mass lateralization seen on MRI. Cortical hypometabolism showed three patterns depending whether the HH mass involved mammillary bodies, middle hypothalamus nucleus, or both. The three patterns were hypometabolism of the mesial temporal cortex with symptom of mesial temporal epilepsy (3/16, pattern I), lateral temporal, and extratemporal (frontal or parietal) cortex with symptom of neocortex temporal or frontal epilepsy (5/16, pattern II), and mesial and lateral temporal cortex and extratemporal (frontal or parietal) cortex with varied symptoms (8/16, pattern III), respectively. A significant difference in PET voxel values was found between bilateral hippocampal formation ( P = 0.001) and lateral temporal neocortex in the third group ( P = 0.005). We suggest that the hypometabolic characteristics of the extra-hypothalamic cortex in HH patients have three patterns. The final cortical hypometabolic pattern depends on the neuroanatomic location of the HH mass and was consistent with the main involved cortex of the interictal and ictal discharges. The third hypometabolic pattern with the most extensive cortical hypometabolism has a poorer prognosis., 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 Yang, Wei, Meng, An, Fan, Wang, Wang, Ren, Shan and Zhao.)

Co-selection of antibiotic resistance genes (ARGs) by heavy metals might facilitate the spread of ARGs in the environments. Cadmium contamination is ubiquitous, while, it remains unknown the extent to which cadmium (Cd 2+ ) impact plasmid-mediated transfer of ARGs in aquatic bacterial communities. In the present study, we found that Cd 2+ amendment at sub-inhibitory concentration significantly increased conjugation frequency of RP4 plasmid from Pseudomonas putida KT2442 to a fresh water microbial community by liquid mating method. Cd 2+ treatment (1-100 mg/L) significantly increased the cell membrane permeability and antioxidant activities of conjugation mixtures. Amendments of 10 and 100 mg/L Cd 2+ significantly enhanced the mRNA expression levels of mating pair formation gene (trbBp) and the DNA transfer and replication gene (trfAp) due to the repression of regulatory genes (korA, korB and trbA). Phylogenetic analysis of transconjugants indicated that Proteobacteria was the dominant recipients and high concentration of Cd 2+ treatment resulted in expanded recipient taxa. This study suggested that sub-inhibitory Cd 2+ contamination would facilitate plasmid conjugation and contributed to the maintenance and spread of plasmid associated ARGs, and highlighted the urgent need for effective remediation of Cd 2+ in aquatic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Recent studies have shown the challenges involved in detecting small conflicting vessels (1.0-1.5 mm) on contrast-enhanced (CE) T1 images during stereoelectroencephalography (SEEG) planning. Improving the resolution of non-invasive approaches to identify these vessels is possible and important. We present a superior sagittal sinus mapping-based CE-magnetic resonance venography (CE-MRV) protocol calibrated by craniotomies., Method: Seven patients with epileptic symptoms who received craniotomy were enrolled. CE-MRV was acquired with a bolus mapping of the superior sagittal sinus. Together with the T1 image, 3D veins and the brain surface were visualized. The resolution of the CE-MRV was quantified by measuring the diameter of superficial drainages after exposure of the brain surface during craniotomy., Results: A total of 37 superficial drainages were exposed in the bone windows. CE-MRV visualized all these drainages. On average, one superficial drainage could be found in every 13.2 mm diameter of the bone window. The boundary resolution of the CE-MRV was 0.58-0.8 mm in vessel diameter, while drainages larger than 0.8 mm were visualized consistently., Conclusions: The resolution of the CE-MRV in the present study met the requirement for detection of small conflicting vessels during SEEG planning. The visualized venous landmarks could be used for visual guidance to the surgical zone. As a non-invasive approach, CE-MRV is practical to use in the clinical setting.

Pulmonary artery systolic pressure (PASP) may increase because of cardiac alterations that result in increased filling pressures after acute myocardial infarction (AMI). We hypothesized that PASP might be a useful maker to predict the risk of cardiac death after AMI. We carried out a retrospective study from 2013 to 2017 involving 5401 patients with AMI. Patients were grouped according to their admission PASP result, and the primary end point was cardiac death in 6 months after AMI. Pulmonary artery systolic pressure was associated with age, AMI site, Killip classification, and decreased ejection fraction. After adjustments for clinical and echocardiographic parameters in a Cox model, PASP was found to be significantly related to cardiac death. In receiver operating characteristic analysis, PASP >30 mm Hg had a sensitivity of 59.8% and a specificity of 62.5% for predicting 6-month cardiac death after AMI. In conclusion, PASP at the index admission may be a useful marker predicting short-term cardiac death. These results have implications for future research and management of patients with AMI.

Background: Introducing multiple different stereoelectroencephalography electrodes in a three-dimensional (3D) network to create a 3D-lesioning field or stereo-crossed radiofrequency thermocoagulation (scRF-TC) might create larger lesioning size; however, this has not been quantified to date. This study aimed to quantify the configurations essential for scRF-TC., Methods: By using polyacrylamide gel (PAG), we investigated the effect of electrode conformation (angled/parallel/multiple edges) and electrode distance of creating an electrode network. Volume, time, and temperature were analyzed quantitatively with magnetic resonance imaging, video analysis, and machine learning. A network of electrodes to the pathological left area 47 was created in a patient; the seizure outcome and coverage range were further observed., Results: After the compatibility test between the PAG and brain tissue, the sufficient distance of contacts (from different electrodes) for confluent lesioning was 7 mm with the PAG. Connection to the lesioning field could be achieved even with a different arrangement of electrodes. One contact could achieve at least six connections with different peripheral contacts. Coagulation with a network of electrodes can create more significant lesioning sizes, 1.81-2.12 times those of the classic approaches. The confluent lesioning field created by scRF-TC had a volume of 38.7 cm 3 ; the low metabolic area was adequately covered. The representative patient was free of seizures throughout the 12-month follow up., Conclusion: Lesioning with electrodes in a network manner is practical for adequate 3D coverage. A secondary craniotomy could be potentially prevented by combining both monitoring and a large volume of lesions., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Objective: Fibrosis stage is strongly associated with liver-related outcomes and is a key surrogate endpoint in drug trials for non-alcoholic steatohepatitis. Dual-photon microscopy allows automated quantification of fibrosis-related parameters (q-FPs) and may facilitate large-scale histological studies. We aim to validate the performance of q-FPs in a large histological cohort., Design: 344 patients with non-alcoholic fatty liver disease (NAFLD) underwent 428 liver biopsies (240 had paired transient elastography examination). Fibrosis stage was scored using the NASH Clinical Research Network system, and q-FPs were measured by dual-photon microscopy using unstained slides. Patients were randomly assigned to the training and validation cohorts to test the performance of individual q-FPs and derive optimal cut-offs., Results: Over 25 q-FPs had area under the receiver-operating characteristics curves >0.90 for different fibrosis stages. Among them, the perimeter of collagen fibres and number of long collagen fibres had the highest accuracy. At the best cut-offs, the two q-FPs had 88.3%-96.2% sensitivity and 78.1%-91.1% specificity for different fibrosis stages in the validation cohort. q-FPs and histological scoring had nearly identical correlations with liver stiffness measurement, suggesting that the accuracy of q-FPs approached that of histological assessment. Among patients with paired liver biopsies, changes in the same q-FPs were associated with changes in fibrosis stage. At a median follow-up of 5.6 years, baseline q-FPs predicted liver-related events., Conclusion: q-FP is highly accurate in the assessment of fibrosis in NAFLD patients. This automated platform can be used in future studies as objective and reliable evaluation of histological fibrosis., Competing Interests: Competing interests: VW-SW has served as an advisor/consultant for AbbVie, Allergan, Echosens, Gilead Sciences, Janssen, Novo Nordisk, Perspectum Diagnostics, Pfizer and Terns; and a speaker for Bristol-Myers Squibb, Echosens, Gilead Sciences and Merck. GL-HL-HW and HLYC have served as speakers for Echosens. The other authors report no conflict of interests., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aldehyde is one of most synthetically versatile functional groups and can participate in numerous chemical transformations. While a variety of simple aromatic aldehydes are commercially available, those with a more complex substitution pattern are often difficult to obtain. Benzylic oxygenation of methylarenes is a highly attractive method for aldehyde synthesis as the starting materials are easy to obtain and handle. However, regioselective oxidation of functionalized methylarenes, especially those that contain heterocyclic moieties, to aromatic aldehydes remains a significant challenge. Here we show an efficient electrochemical method that achieves site-selective electrooxidation of methyl benzoheterocycles to aromatic acetals without using chemical oxidants or transition-metal catalysts. The acetals can be converted to the corresponding aldehydes through hydrolysis in one-pot or in a separate step. The synthetic utility of our method is highlighted by its application to the efficient preparation of the antihypertensive drug telmisartan.

Background: Gastric bypass (GB) and sleeve gastrectomy (SG) are two common types of bariatric surgery that carry many potential complications. Among these complications, bone metabolism-related diseases have attracted substantial attention; however, no meta-analysis of them has been performed to date., Methods: We searched PubMed, Web of Science, The Cochrane Library, and Embase to identify relevant studies published before January 2019. The following indicators were evaluated: serum parathyroid hormone (PTH), calcium, phosphorus and 25-hydroxyvitamin D levels, body mass index (BMI), and bone mineral density (BMD)., Results: Thirteen studies met our inclusion criteria. Overall results showed that patients undergoing GB had lower levels of 25-hydroxyvitamin D (MD = - 1.85, 95% CI (- 3.32, - 0.39) P = 0.01) and calcium (MD = - 0.15, 95% CI (- 0.24, - 0.07) P = 0.0006) as well as higher levels of PTH (MD = 3.58, 95% CI (0.61, 7.09) P = 0.02) and phosphorus (MD = 0.22, 95% CI (0.10, 0.35) P = 0.0005). The results of BMI and BMD were comparable in each group., Conclusion: Our meta-analysis suggested that obese patients undergoing GB had lower levels of serum calcium and 25-hydroxyvitamin D as well as higher levels of serum phosphorus and PTH. To prevent postoperative bone metabolism-related diseases, appropriate postoperative interventions should be undertaken for particular surgical procedures.

Background: Visual field defects caused by injury to Meyer's loop (ML) are common in patients undergoing anterior temporal lobectomy during epilepsy surgery. Evaluation of the anatomical shapes of the curving, fanning and sharp angles of ML to guide surgeries is important but still challenging for diffusion tensor imaging. We present an advanced diffusion data-based ML atlas and labeling protocol to reproduce anatomical features in individuals within a short time., Methods: Thirty Massachusetts General Hospital-Human Connectome Project (MGH-HCP) diffusion datasets (ultra-high magnetic gradient & 512 directions) were warped to standard space. The resulting fibers were projected together to create an atlas. The anatomical features and the tractography correspondence rates were evaluated in 30 MGH-HCP individuals and local diffusion spectrum imaging data (eight healthy subjects and six hippocampal sclerosis patients)., Results: In the atlas, features of curves, sharp angles and fanning shapes were adequately reproduced. The distances from the anterior tip of the temporal lobe to the anterior ridge of Meyer's loop were 23.1 mm and 26.41 mm on the left and right sides, respectively. The upper and lower divisions of the ML were revealed to be twisting. Eighty-eight labeled sides were achieved, and the correspondence rates were 87.44% ± 6.92, 80.81 ± 10.62 and 72.83% ± 14.03% for MGH-HCP individuals, DSI-healthy individuals and DSI-patients, respectively., Conclusion: Atlas-labeled ML is comparable to high angular resolution tractography in healthy or hippocampal sclerosis patients. Therefore, rapid identification of the ML location with a single modality of T1 is practical. This protocol would facilitate functional studies and visual field protection during neurosurgery.

Objective: To observe the position of the electrode in the cochlea following cochlear implantation by cone beam computed tomography (CBCT). Methods: Twenty-five children who received cochlear implantation and CBCT examinations in the Department of Otorhinolaryngology Head and Neck Surgery from the Second Hospital of Shandong University between January 2016 and December 2017 were selected. There were 15 males (17 ears) and 10 females (10 ears). The age ranged from 0.5 to 7.0 years old, with a median age of 1.6 years. 23 patients with unilateral implantation and two patients with bilateral implantation. The implants were all Med-El standard 12-electrode contact arrays. The CBCT was used to determine the position of the electrode in the cochlea, the distance between the electrode contacts and modiolus, and intracochlear insertion length of the electrode arrays. SPSS Statistics, version 22.0 was used for data processing and statistical analysis. Results: CBCT images could clearly demonstrate the structure of round window, oval window, modiolus, osseous cochlear duct, osseous spiral lamina, and electrodes. The electrode arrays of all the children were fully implanted into the cochlea. 26 of the electrode arrays were located in the scala tympani and one of them was inserted into the scala vestibular. The mean intracochlear insertion length of the electrode arrays was 30.23 (95 %CI , 30.04-30.71) mm. The distance between the electrode contacts and modiolus gradually increased at the 1-4th electrode contacts and reached the maximum at the 4th electrode contacts with an average of 1.10 mm (95 %CI , 1.02 to 1.18 mm), and then gradually decreased from the 5th electrode contacts. Conclusions: CBCT can clearly show cochlear fine structures and therefore accurately assess the electrode position following cochlear implantation.

Fuhuan point of Zhuang medicine is a set of point distributed as circle form, it is a common point in Zhuang medicine. In this paper, Fuhuan point of Zhuang medicine was analyzed from the following five aspects, i.e. basic theory, location, affiliation to heaven, earth and human being, main usage and principles of point combinations. Zhuang medicine believes that the Fuhuan point is located in the middle of human body, where the essence of heaven and earth converges. Fuhuan point is closely connected with dragon and fire systems as well as zang-fu organs in Zhuang medicine, it acts on promoting circulation, adjusting qi and blood, and treating various diseases. It is highly valuable in clinical application.

Bilayer graphene consists of two stacked graphene layers bound together by van der Waals interaction. As the molecular analog of bilayer graphene, molecular bilayer graphene (MBLG) can offer useful insights into the structural and functional properties of bilayer graphene. However, synthesis of MBLG, which requires discrete assembly of two graphene fragments, has proved to be challenging. Here, we show the synthesis and characterization of two structurally well-defined MBLGs, both consisting of two π-π stacked nanographene sheets. We find they have excellent stability against variation of concentration, temperature and solvents. The MBLGs show sharp absorption and emission peaks, and further time-resolved spectroscopic studies reveal drastically different lifetimes for the bright and dark Davydov states in these MBLGs.

Objective: To evaluate the effect of intranasal immunization with CTA1-DD as mucosal adjuvant combined with H3N2 split vaccine., Methods: Mice were immunized intranasally with PBS (negative control), or H3N2 split vaccine (3 μg/mouse) alone, or CTA1-DD (5 μg/mouse) alone, or H3N2 split vaccine (3 μg/mouse) plus CTA1-DD (5 μg/mouse). Positive control mice were immunized intramuscularly with H3N2 split vaccine (3 μg/mouse) and alum adjuvant. All the mice were immunized twice, two weeks apart. Then sera and mucosal lavages were collected. The specific HI titers, IgM, IgG, IgA, and IgG subtypes were examined by ELISA. IFN-γ and IL-4 were test by ELISpot. In addition, two weeks after the last immunization, surivival after H3N2 virus lethal challenge was measured., Results: H3N2 split vaccine formulated with CTA1-DD could elicit higher IgM, IgG and hemagglutination inhibition titers in sera. Furthermore, using CTA1-DD as adjuvant significantly improved mucosal secretory IgA titers in bronchoalveolar lavages and vaginal lavages. Meanwhile this mucosal adjuvant could enhance Th-1-type responses and induce protective hemagglutination inhibition titers. Notably, the addition of CTA1-DD to split vaccine provided 100% protection against lethal infection by the H3N2 virus., Conclusion: CTA1-DD could promote mucosal, humoral and cell-mediated immune responses, which supports the further development of CTA1-DD as a mucosal adjuvant for mucosal vaccines., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Plasmid conjugation is one of the dominant mechanisms of horizontal gene transfer, playing a noticeable role in the rapid spread of antibiotic resistance genes (ARGs). Broad host range plasmids are known to transfer to diverse bacteria in extracted soil bacterial communities when evaluated by filter mating incubation. However, the persistence and dissemination of broad range plasmid in natural soil has not been well studied. In this study, Pseudomonas putida with a conjugative antibiotic resistance plasmid RP4 was inoculated into a soil microcosm, the fate and persistence of P. putida and RP4 were monitored by quantitative PCR. The concentrations of P. putida and RP4 both rapidly decreased within 15-day incubation. P. putida then decayed at a significantly lower rate during subsequent incubation, however, no further decay of RP4 was observed, resulting in an elevated RP4/ P. putida ratio (up to 10) after 75-day incubation, which implied potential transfer of RP4 to soil microbiota. We further sorted RP4 recipient bacteria from the soil microcosms by fluorescence-activated cell sorting. Spread of RP4 increased during 75-day microcosm operation and was estimated at around 10 -4 transconjugants per recipient at the end of incubation. Analysis of 16S rRNA gene sequences of transconjugants showed that host bacteria of RP4 were affiliated to more than 15 phyla, with increased diversity and shift in the composition of host bacteria. Proteobacteria was the most dominant phylum in the transconjugant pools. Transient transfer of RP4 to some host bacteria was observed. These results emphasize the prolonged persistence of P. putida and RP4 in natural soil microcosms, and highlight the potential risks of increased spread potential of plasmid and broader range of host bacteria in disseminating ARGs in soil.

Studies of nesfatin-1 in glucose metabolism have become a topic of interest recently, however, the specific receptor for nesfatin-1 has not yet been identified. Some studies hinted at a connection between nesfatin-1 and the ghrelin receptor, growth hormone secretagogue receptor. Therefore, we aimed to study the role of GHSR in the glycemic effects of nesfatin-1 as well as its downstream pathways. We employed C57/BL6 mice (wild type and GHSR knockout mice) eating a normal chow diet and a high fat diet in this study, and the experimental technique included western blot, real-time PCR, immunofluorescence and ELISA. We found that in mice fed a normal chow diet (NCD), nesfatin-1 improved glucose tolerance, up-regulated AKT kinase (AKT) mRNA levels and phosphorylation and GLUT4 membrane translocation in skeletal muscle. These effects were blocked by co-injection of GHSR antagonist [D-Lys3]-GHRP-6 and were attenuated in GHSR knockout mice. In mice fed high-fat diet (HFD), nesfatin-1 not only exerted the effects observed in NCD mice, but also suppressed appetite and raised AKT levels in liver tissues that also required GHSR. Peripheral nesfatin-1 suppressed c-fos expression of GHSR immunoreactive neurons induced by fasting in hypothalamic nuclei, indicating that nesfatin-1 inhibited the activation of central GHSR. We concluded that the effects of nesfatin-1 on food intake and glucose metabolism were GHSR-dependent, and that the glycemic effect was associated with AKT and GLUT4. This study should stimulate further exploration of the nesfatin-1 receptor.

Ebola virus (EBOV) disease (EVD) leads to lethal hemorrhagic fever with a case fatality rate as high as 90%, thus posing a serious global public health concern. However, while several vaccines based on the EBOV glycoprotein have been confirmed to be effective in animal experiments, no licensed vaccines or effective treatments have been approved since the first outbreak was reported in 1976. In this study, we prepared the extracellular domain of the EBOV GP protein (designated as N20) by prokaryotic expression and purification via chromatography. Using CTA1-DD (designated as H45) as a mucosal adjuvant, we evaluated the immunogenicity of N20 by intranasal administration and the associated protective efficacy against mouse-adapted EBOV challenge in mice. We found that intranasal vaccination with H45-adjuvanted N20 could stimulate humoral immunity, as supported by GP-specific IgG titers; Th1 cellular immunity, based on IgG subclasses and IFN-γ/IL-4 secreting cells; and mucosal immunity, based on the presence of anti-EBOV IgA in vaginal lavages. We also confirmed that the vaccine could completely protect mice against a lethal mouse-adapted EBOV (MA-EBOV) challenge with few side effects (based on weight loss). In comparison, mice that received N20 or H45 alone succumbed to lethal MA-EBOV challenge. Therefore, mucosal vaccination with H45-adjuvanted N20 represents a potential vaccine candidate for the prevention of EBOV in an effective, safe, and convenient manner., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: In the detection of seizure onset zones, arterial spin labeling (ASL) can overcome the limitations of positron emission tomography (PET) with 18 F-fluorodeoxyglucose ( 18 F-FDG), which is invasive, expensive, and radioactive. PET/magnetic resonance (MR) systems have been introduced that allow simultaneous performance of ASL and PET, but comparisons of these techniques with stereoelectroencephalography (SEEG) and comparisons among the treatment outcomes of these techniques are still lacking. Here, we investigate the effectiveness of ASL compared with that of SEEG and their outcomes in localizing mesial temporal lobe epilepsy (MTLE) and assess the correlation between simultaneously acquired PET and ASL., Methods: Between October 2016 and August 2017, we retrospectively studied 12 patients diagnosed with pure unilateral MTLE. We extracted and quantitatively computed values for ASL and PET in the bilateral hippocampus. SEEG findings and outcome were considered the gold standard of lateralization. Finally, the bilateral asymmetry index (AI) was calculated to assess the correlation between PET and ASL., Results: Our results showed that hypoperfusion in the hippocampus detected using ASL matched the SEEG-defined epileptogenic zone in this series of patients. The mean normalized voxel value of ASL in the contralateral hippocampus was 0.97 ± 0.19, while in the ipsilateral hippocampus, it was 0.84 ± 0.14. Meanwhile, significantly decreased perfusion and metabolism were observed in these patients (Wilcoxon, p  < 0.05), with a significant positive correlation between the AI values derived from PET and ASL (Pearson's correlation, r  = 0.74, p  < 0.05)., Significance: In our SEEG- and outcome-defined patients with MTLE, ASL could provide significant information during presurgical evaluation, with the hypoperfusion detected with ASL reliably lateralizing MTLE. This non-invasive technique may be used as an alternative diagnostic tool for MTLE lateralization.

Background: The use of magnetic resonance imaging (MRI)-guided ablation methods, such as laser interstitial thermal therapy and MRI-guided radiofrequency thermocoagulation (RF-TC), poses a risk of mistreatment in patients with nonepileptic hypothalamic hamartoma (HH). Using stereoelectroencephalography (SEEG)-guided RF-TC could solve this problem; however, there are no reports on the efficacy of this technique. Thus, we examined the safety and efficacy of this method., Methods: This retrospective study was conducted in 9 consecutive patients with HH treated between August 2015 and July 2017. All patients underwent a single round of SEEG-guided RF-TC treatment after comprehensive assessment. Outcomes were assessed using Engel's classification system. Spearman's correlation and receiver operating characteristic curves were analyzed to identify potential factors predictive of seizure outcome after an average follow-up duration of 18.78 months., Results: A total of 20 SEEG electrodes were implanted in 9 patients with HH, and 73 lesions were created within the tumors. No obvious symptoms were observed during coagulation. Five patients (55.56%) achieved Engel's class I recovery, and the other 4 (44.44%) achieved Engel's class II recovery; weight gain was observed in 1 patient. Correlation analysis revealed a trend of better seizure outcomes for larger-sized tumors., Conclusions: The SEEG signal can guide ablation of HH. SEEG-guided RF-TC is a safe procedure that shows promising efficacy. Special attention to the tumor attachment and multiple rounds of RF-TC might help improve seizure-free rates in the future., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To eliminate the side effects of aluminum adjuvant and His-tag, we constructed chimeric VLPs displaying the epitope of EV71 (SP70) without His-tagged. Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant., Methods: The fusion protein was constructed by inserting SP70 into the MIR of truncated HBcAg sequence, expressed in E. Coli, and purified through ion exchange chromatography and density gradient centrifugation. Mice were immunized with the VLPs and sera were collected afterwards. The specific antibody titers, IgG subtypes and neutralizing efficacy were detected by ELISA, neutralization assay, and EV71 lethal challenge. IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay., Results: HBc-SP70 proteins can self-assemble into empty VLPs. After immunization with HBc-SP70 VLPs, the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge. There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not. The specific IgG subtypes were mainly IgG1 and IgG2b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4., Conclusion: The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation. In the absence of adjuvant, they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant. Furthermore, the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Currently, increasing importance has been attached to heavy metal pollution of water environment. In order to help geologist and environmentalist to obtain on-site experimental data, there is an urgent need to develop portable analysis techniques of water quality, which can be used to give an timely and accurate assessment of water quality of the contaminated area with low cost and to monitor water environment conveniently in daily preventing and controlling work of water pollution. Based on adsorption with Purolite S930 chelating resin at pH 4 and thin-film sample preparation technique, a rapid and simple on-site-oriented analysis method of heavy metal ions, namely Mn, Fe, Ni, Cu, Zn and Pb in aqueous solutions, was developed utilizing a handheld energy-dispersive X-ray fluorescence in this paper. The correlation coefficients of the calibration curves were greater than 0.992 for all six metal ions, the lower limits of detection were between 5.8 and 18.6 μg·L-1. Precision tests carried out on multi-element mixed solutions showed that the relative standard deviations (RSD, n=10) were better than 15%. The method has been used on-site to analysis 21 water samples collected from different river or well sites near a mining area northeast China. Out of the five underground water samples one was found contaminated by Cu and Zn (Class Ⅲ), one by Zn and Fe (Class Ⅱ), and one by Fe(in between Class Ⅱ to Ⅲ). Surface water samples showed better qualities. But two out of the sixteen were found to be contaminated by Mn heavily (Class Ⅳ). Laboratory ICPMS was used to analyze the same samples. The results for Cu, Ni and Pb were coincident with the on-site data in general. But for Zn and Mn with higher concentrations, on-site data were lower than that by ICPMS. The reason for that might be the inclusion of the fine suspending particles in the samples by ICPMS. We conclude that the on-site data were effective. With the described method, an overall data acquisition time, including sampling, processing and measuring, can be within 12 hours for a batch of 10 samples. The pre-concentration device and the XRF instrument are both small, light, portable and can operate without external power supply. So, the method is suitable for on-site water sample analysis, especially in remote areas.

The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.