Risks of bleeding and thromboembolic events in patients undergoing colonoscopy on uninterrupted and interrupted anticoagulant therapy in real-world setting.

BACKGROUND: Although anticoagulants may potentially increase the risk of post-colonoscopy bleeding events, temporary discontinuation of medications could elevate the risk of thromboembolism (TE). There is a paucity of data regarding the incidence of bleeding and TE events in patients undergoing colonoscopy while on uninterrupted or interrupted anticoagulant therapy. Therefore, we aimed to ascertain the risks of post-colonoscopy TE and bleeding in patients with continuous or interrupted use of anticoagulant agents. METHODS: The electronic databases of PubMed, Embase, and the Cochrane library were comprehensively searched from inception to March 15, 2024. We identified studies reporting the incidence of bleeding and TE events in patients undergoing colonoscopy with uninterrupted or interrupted anticoagulant therapy. The pooled incidence rate of bleeding and TE events was estimated using a random-effects model. RESULTS: This study included a total of 15 studies involving 63, 017 patients. Overall, the incidence of post-procedural bleeding for uninterrupted and interrupted direct oral anticoagulants (DOACs) was found to be 3.60 % (95 % CI: 1.60 %-5.60 %), and 0.90 % (95 % CI: 0.10 %-10.30 %), respectively. Subgroup analysis revealed that older age patients (≥65 years) had a significantly higher rate of bleeding with uninterrupted DOACs therapy compared to younger age patients (< 65 years) (7.20 % vs. 2.00 %). The highest rate of bleeding was observed in Asia (7.20 %, 95 % CI: 2.20 %-12.10 %). Similarly, the risk of bleeding was significantly increased among patients interrupting DOACs therapy in Asia compared to North America (1.40 % vs. 0.26 %). For patients on uninterrupted and interrupted warfarin, a higher rate of bleeding events was observed in older age patients than younger age patients (4.90 % vs. 0.80 %, and 2.20 % vs. 1.70 %, respectively). Uninterrupted warfarin showed a more significant risk of bleeding in Asia (4.20 %, 95%CI: 1.90 %-6.60 %) compared to North America (1.00 %, 95%CI: 0.50 %-1.50 %). Among those who did not interrupt DOACs therapy, the incidence of TE was the lowest (0.08 %, 95%CI: 0.04 %-0.11 %). CONCLUSION: This study provides a comprehensive assessment of bleeding and TE risks in patients undergoing colonoscopy while receiving uninterrupted or interrupted anticoagulant therapy in the real-world setting. The overall incidence of post-colonoscopy bleeding and TE events is relatively low. However, the uninterrupted DOACs and warfarin are associated with an elevated risk of bleeding, particularly among elderly patients and the Asian population.

Low platinum loading electrocatalyst supported on a carrier derived from carbon dots doped ZIF-67 for the ORR and zinc-air batteries.

The development of economical and efficient platinum-based catalysts for the oxygen reduction reaction (ORR) is considered the most promising strategy for the widespread application of clean energy conversion devices. Herein, Co nanoparticles encapsulated in N-doped carbon carriers, CoCN(CDs-X), were constructed by pyrolyzing carbon dots (CDs) doped ZIF-67 and further used to anchor Pt to prepare low Pt loading catalysts, PtCoCN(CDs-X). The introduction of CDs not only improves the conductivity for efficient electron transfer, but also regulates the interaction between Pt and the CoCN(CDs-X) support and alleviates the oxidation of Pt. The optimized PtCoCN(CDs-0.10) displays decent ORR behavior with onset and half-wave potentials of 0.95 V and 0.83 V, respectively, in alkaline media and superior catalytic stability and methanol tolerance. While employing PtCoCN(CDs-0.10) as a cathode catalyst for an as-assembled zinc-air battery (ZAB), it delivers an excellent power density of 194.2 mW cm-2 and exceptional operation stability, which is indicated by a voltage efficiency loss of only 7.7% after a long cycle life of 100 h, demonstrating its great potential applications.

Demethylation of lignin with mild conditions and preparation of green adhesives to reduce formaldehyde emissions and health risks.

Demethylated lignin (DL) was prepared in a NaOH/urea solution at room temperature, and the DL solution was directly substituted for phenol to prepare demethylated lignin phenol formaldehyde (DLPF). The 1H NMR results showed that the benzene ring's -OCH3 content dropped from 0.32 mmol/g to 0.18 mmol/g, whereas the functional group content of the phenolic hydroxyl group increased by 176.67 %, increasing the reactivity of DL. The bonding strength of 1.24 MPa and formaldehyde emission of 0.059 mg/m3 met the Chinese national standard with a 60 % replacement of DL with phenol. The volatile organic compound (VOC) emissions of DLPF and PF were simulated, with 25 types of VOCs were found in PF plywood and 14 types found in DLPF plywood. Terpene and aldehyde emissions from DLPF plywood rose, but total VOC emissions were 28.48 % less than those from PF. For carcinogenic risks (CR), both PF and DLPF showed ethylbenzene and naphthalene as carcinogenic VOCs, whereas DLPF had a lower total CR of 6.50 × 10-5. Both plywood had a noncarcinogenic risks of <1, which was within the permissible range to harm humans. In this study, the mild modification conditions of DL benefit its large-scale production, and DLPF effectively reduces the VOCs released from plywood in indoor environments, diminishing the health risks to humans.

Factors Influencing the Interruption of Nursing Document Writing in the Intensive Care Unit: A Cross-Sectional Survey.

Objective: To explore the current status of interruption events in nursing document writing in the intensive care unit (ICU) using a cross-sectional survey. Methods: Between May and October 2021, the convenience sampling method was used to observe the interruption events in nursing document writing in the ICU. A total of 54 nurses and 7 indicators were observed: the start time, end time, interruption period, source, type, duration and outcome of interruption events. Results: A total of 438 interruption events in nursing document writing occurred in 85.955 hours, with a frequency of 5.093 times/hour and a duration of 4787.00 (1152.00, 13,109.00) seconds. The frequency of interruption events in nursing document writing was the highest (11 times/hour) and the duration was the longest (9581.50 seconds) from 08:00 to 12:00. The main sources of interruptions for nurses with 10 or more years of service or with the professional title of nurse are nurses themselves and their colleagues. The main sources of interruptions for nurses who have been in charge for 10 years or over are the working environment and doctors. This intervention in work continuity occurs unexpectedly; however, if adjustments are made to nursing procedures, the interruption can be terminated rapidly or adverse consequences can be avoided. Years of working experience, seniority level, interruption time periods and professional titles were independent factors influencing the number of interruption events, and they were all positively correlated. The results of this study show that there were statistically significant differences in the incidence of negative outcomes among ICU nurses with varying years of working experience and professional titles. Conclusion: Interruptions in nursing document writing have high frequency, complex sources and multiple types. For senior nurses, the outcome was predominantly positive, while for junior nurses, it was predominantly negative.

Controlling the Nonlinear Optical Behavior and Structural Transformation with A-Site Cation in α-AZnPO4 (A = Li, K).

Regulating the crystal structure by A-site cation substitution is one of the effective methods to explore high-performance nonlinear optical (NLO) materials. Herein, two non-centrosymmetric (NCS) compounds, α-MZnPO4 (M = Li, K) with short UV absorption edges 221 and 225 nm, are obtained by performing A-site cation substitution method. It is noteworthy that α-LiZnPO4 (α-LZPO) achieves >10 times second harmonic generation (SHG) response (2.3 × KDP) enhancement compared with that of α-KZnPO4 (α-KZPO) (0.2 × KDP), which is the only case among phosphates with different A-site cations. By structural comparison, it is found that the A-site cations play important roles for anion rearrangements, and further the structure features of the two compounds by designing two suppositional crystal models as well as performing other theoretical calculations are analyzed. The study confirms the feasibility to design promising NLO materials with strengthen SHG response and structural stability in orthophosphate system.

Well-dispersed Ni3Fe nanoparticles with a N-doped porous carbon shell for highly efficient rechargeable Zn-air batteries.

NiFe-based nanoparticles attached to heteroatom-doped carbon are found to act as tremendously efficient oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalysts. Nevertheless, it is extremely challenging to control the particle size and avoid aggregation. Herein, nitrogen-doped carbon encapsulated Ni3Fe nanoparticles (Ni3Fe@NC) are prepared by two-stage pyrolysis with a low rate based on the in situ structural evolution of FeNi-PBAs. The strategy results in uniform Ni3Fe nanoparticles anchoring within the carbon shell and thus facilitating interfacial interaction. Benefiting from the enhanced synergism between Ni3Fe particles and NC layers, Ni3Fe@NC-600 demonstrates the best catalytic activity and durability, not only with almost the same onset potential (1.01 V) as commercial Pt/C for the ORR but also satisfactory OER performance with a low overpotential of 0.29 V at 10 mA cm-2 in 0.1 M KOH. Moreover, the Zn-air battery assembled using the Ni3Fe@NC-600 cathode exhibits superior performance to commercial Pt/C + RuO2. The simple and scalable method of this work provides insight into the fabrication of high-performance and cost-effective bifunctional oxygen electrocatalysts.

Combined Activity of Saponin B Isolated from Dodonaea viscosa Seeds with Pesticide Azadirachtin against the Pest Spodoptera litura.

Azadirachtin is regarded as one of the best botanical pesticides due to its broad spectrum of insecticides and low interference with natural enemies. To enhance the effect of azadirachtin and slow down the generation of resistance, the combined activity was studied. Here, we found that Dodonaea viscosa saponin B (DVSB) isolated from the seeds of Dodonaea viscosa has good combined activity with the azadirachtin. The mixture of DVSB and azadirachtin in a volume ratio of 1:4 had the strongest combined effect against Spodoptera litura, with a co-toxicity coefficient (CTC) of 212.87. DVSB exerted its combined activity by affecting the contact angle, surface tension, maximum retention and cell membrane permeability. When mixed with DVSB, the contact angle and surface tension decreased by 30.38% and 23.68%, and the maximum retention increased by 77.15%. DVSB was screened as an effective combined activity botanical compound of azadirachtin upon the control of S. litura and highlights the potential application of botanical compounds as pesticide adjuvants in the pest management.

Pseudomonas lijiangensis sp. nov., a novel phytopathogenic bacterium isolated from black spots of tobacco.

Three Gram-stain-negative, motile, with amphilophotrichous flagella, and rod-shaped bacteria (LJ1, LJ2T and LJ3) were isolated from lower leaves with black spots on flue-cured tobacco in Yunnan, PR China. The results of phylogenetic analysis based on 16S rRNA gene sequences indicate that all the strains from tobacco were closely related to the type strains of the Pseudomonas syringae group within the P. fluorescens lineage and LJ2T has the highest sequence identities with P. cichorii DSM 50259T (99.92 %), P. capsici Pc19-1T (99.67 %) and P. ovata F51T (98.94 %) . The 16S rRNA gene sequence identities between LJ2T and other members of the genus Pseudomonas were below 98.50%. The average nucleotide identity by blast (ANIb) values between LJ2T and P. cichorii DSM 50259T, P. capsici Pc19-1T and P. ovata F51T were less than 95 %, and the in silico DNA-DNA hybridization (isDDH) values (yielded by formula 2) were less than 70 %. The major fatty acids were C16  :  1ω7c and/or C16  :  1ω6c (summed feature 3), C16  :  0 and C18  :  1ω7c and/or C18  :  1ω6c (summed feature 8). The polar lipids profile of LJ2T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified phospholipids and one unidentified glycolipid. The predominant respiratory quinone was Q-9. The DNA G+C content of LJ2T was 58.4 mol%. On the basis of these data, we concluded that LJ2T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas lijiangensis sp. nov. is proposed. The type strain of Pseudomonas lijiangensis sp. nov. is LJ2T (=CCTCC AB 2021465T=GDMCC 1.2884T=JCM 35177T).

Effect of Cognitive-Behavioral Therapy or Mindfulness Therapy on Pain and Quality of Life in Patients with Diabetic Neuropathy: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aimed to evaluate the effectiveness of cognitive behavioral therapy (CBT) and mindfulness therapy (MT) for pain relief and quality of life (QOL) in patients with diabetic neuropathy. REVIEW/ANALYSIS METHODS: Four databases were systematically searched from their respective inception dates to 29 June 2021. Relevant randomized controlled trials (RCTs) were screened and assessed for risk of bias. Eight RCTs evaluating CBT or MT were included. Statistical analysis was performed using Review Manager 5.4. RESULTS: Eight RCTs involving 384 patients with painful diabetic neuropathy (PDN) tested psychological interventions, including three CBT and five MT studies. The results showed that patients' pain severity (standardized mean difference [SMD] = -0.60, 95% confidence interval [CI; -0.93 to -0.27], P = .0003) and QOL (SMD = -0.43, 95% CI [-0.83 to -0.04], p = .03) were improved immediately after treatment. Besides, the pain intensity (SMD = -0.67, 95% CI [-1.37 to 0.03], p = .06), pain interference (SMD = -0.75, 95% CI [-1.20 to -0.30], p = .001) and depressive symptoms (SMD = -0.62, 95% CI [-0.96 to -0.28], p = .0003) were superior to the control group after follow up. The subgroup analysis results of different intervention type showed that the CBT group could immediately improve pain (SMD = -0.44, 95% CI [-0.78 to -0.10], p = .01) after treatment. However, there was no statistically significant difference in the CBT group after follow-up (SMD = -0.15, 95% CI [-0.52 to 0.22], p = .42). CONCLUSIONS: Cognitive behavioral therapy or MT is effective for treating pain in patients with diabetic peripheral neuropathy, improving the QOL, and reducing depressive symptoms. However, large-scale, multi-centre, rigorously designed RCTs are needed to further verify the long-term effects.

First Report of Pectobacterium versatile Causing Stem Rot of Tobacco in China.

Tobacco is one of the most significant non-food cash crops (Lu et al. 2020). In March 2022, cigar tobacco plants showing characteristic symptoms of vascular discoloration, stem rotting, leaf wilting and rotting were observed in Tengchong city (N 25°3'26″, E 98°25'6″) of Yunnan province, China (Fig. S1). The disease incidence was about 5% on cultivar Yunxue 6 in a 33-ha field. Infected stems were collected from Tengchong for pathogen isolation and 16S rDNA sequence analysis was performed as previously described (Lu et al. 2021). Sequence analysis showed that tobacco isolates (GenBank accession numbers: ON795108, ON795107 and ON795106) had an identical sequence with that of the species type strain of Pectobacterium versatile CFBP 6051T and shared the sequence identities of 99.55% and 99.47% with P. carotovorum DSM 30168T and P. parvum s0421T, respectively. Furthermore, phylogenetic analysis showed that tobacco strains were clustered with Pectobacterium versatile CFBP 6051T (Fig. S2a). In API assays, strain 22TC1 was positive for ß-galactosidase activity, reduction of nitrates to nitrites, fermentation of glucose, hydrolysis of esculin and gelatin, assimilation of D-glucose, L-arabinose, D-mannose, D-mannitol, N-acetylglucosamine, malic acid and trisodium citrate; positive for the enzymatic substrates of alkaline phosphatase, leucine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, α-galactosidase, ß-galactosidase and α-glucosidase. Furthermore, the average nucleotide identity (ANI) analysis (Richter et al. 2015) showed that strain 22TC1 (GenBank accession number: JAMWYQ000000000) had the highest ANIb score of 96.76% and ANIm value of 97.19% with P. versatile CFBP 6051T. Similarly, in silico DNA-DNA hybridization (isDDH) value was 74.5% compared to P. versatile CFBP 6051T, isDDH values were 35.5-63.7% with the other Pectobacterium species, which below the 70% threshold value for species delineation (Meier-Kolthoff et al. 2021). The phylogenomic analysis also showed that strain 22TC1 was clustered with the species type strain of P. versatile CFBP 6051T. For pathogenicity tests, cell suspension with ten-fold dilution (approx. 1 x 108 CFU/ml) was injected into the leaf axils of two 2-month-old tobacco stems (cv. Yunyan 87). As a control, tobacco seedlings were inoculated with sterile distilled water. The plants were sealed in plastic bags and maintained in a growth chamber at 28°C for 2 d. The symptoms of water-soaked decay were observed within 24 h of inoculation. Whole-plant decay was at 2 days after injection. No symptoms were developed in the controls. Reisolation was performed on diseased stems and the identity of isolated bacteria was confirmed by PCR and sequencing of 16S rRNA. Similar results were obtained in two independent experiments. Based on the above-described data, the causal pathogen of stem rot on cigar tobacco in Tengchong was identified as P. versatile. To our knowledge, this is the first time that P. versatile is found to cause stem rot on tobacco. Pectobacterium species have been reported to cause seed-borne diseases on tobacco seedlings in the floating tray system and soil-borne diseases in tobacco fields (Wang et al. 2017; Xia and Mo 2007). Therefore, studying the possible transmission of the P. versatile to tobacco plants is necessary.

Ralstonia wenshanensis sp. nov., a novel bacterium isolated from a tobacco field in Yunnan, China.

A Gram-negative, aerobic, motile with paired polar flagella and rod-shaped bacterium strain (56D2T) was isolated from tobacco planting soil in Yunnan, PR China. Major fatty acids were C16  :  1 ω7c (summed feature 3), C16  :  0 and C18  :  1 ω7c (summed feature 8). The polar lipid profile of strain 56D2T consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid and one unidentified glycolipid. Moreover, strain 56D2T contained ubiquinone Q-8 as the sole respiratory quinone. 16S rRNA gene sequence analysis showed that strain 56D2T was closely related to members of the genus Ralstonia and the two type strains with the highest sequence identities were R. mannitolilytica LMG 6866T (98.36 %) and R. pickettii K-288T (98.22 %). The 16S rRNA gene sequence identities between strain 56D2T and other members of the genus Ralstonia were below 98.00 %. Genome sequencing revealed a genome size of 5.87 Mb and a G+C content of 63.7 mol%. The average nucleotide identity values between strain 56D2T and R. pickettii K-288T, R. mannitolilytica LMG 6866 T and R. insidiosa CCUG 46789T were less than 95 %, and the in silico DNA-DNA hybridization values (yielded by formula 2) were less than 70 %. Based on these data, we conclude that strain 56D2T represents a novel species of the genus Ralstonia, for which the name Ralstonia wenshanensis sp. nov. is proposed. The type strain of Ralstonia wenshanensis sp. nov. is 56D2T (=CCTCC AB 2021466T=GDMCC 1.2886T=JCM 35178T).

Tobacco leaf curl Puer virus: a novel monopartite begomovirus infecting Nicotiana tabacum in China.

Begomoviruses (family Geminiviridae) cause serious diseases in many crops. In this study, we characterized a begomovirus isolated from a tobacco plant with leaf curl in Puer, Yunnan Province, China. Analysis of the viral genome obtained from a symptomatic Nicotiana tabacum plant showed that it belonged to a novel monopartite begomovirus. The genome (2741 nt) shared the highest nucleotide sequence identity (83.43%) with that of tomato yellow leaf curl Vietnam virus (TYLCVV). Based on the current taxonomic criteria of the International Committee on Taxonomy of Viruses, this virus, for which the name "tobacco leaf curl Puer virus" is proposed, represents a new species of begomovirus.

NtSWEET1 promotes tobacco resistance to Fusarium oxysporum-induced root rot disease.

Sugars Will Eventually be Exported Transporter (SWEET) is a newly characterized family of sugar transporters, which plays critical roles in plant-pathogen interactions. However, the function of SWEET in tobacco and its interaction with Fusarium oxysporum, a causal agent of root rot, remain unclear. This study aimed to dissect the function of NtSWEETs in tobacco root rot using stem bases from tobacco plants inoculated with F. oxysporum. RNA-sequencing (RNA-Seq) analysis was performed, and the results indicated that Sucrose Transporter 4 (NtSUC4), Sugar Transporter 12 (NtSTP12), Hexose Transporter 6 (NtHEX6), NtSWEET1, NtSWEET3b, and NtSWEET12 were downregulated by infection with F. oxysporum. The expression of NtSWEET1, but not of NtSUC4, NtSTP12, NtHEX6, NtSWEET3b, or NtSWEET12, was suppressed at all the time points tested after inoculation with F. oxysporum. The NtSWEET1-green fluorescent protein was localized on the plasma membrane and possessed the ability to transport glucose, fructose and galactose. Compared with the wild-type plants, NtSWEET1 RNAi plants were more susceptible to root rot, indicating that NtSWEET1 positively regulated the defense of tobacco against root rot. This study identified the role of SWEETs in tobacco and their interaction with F. oxysporum. The results might be useful in protecting tobacco plants from root rot.

Targeted Therapies in Lung Cancers: Current Landscape and Future Prospects.

BACKGROUND: Lung cancer is the most common malignant cancer worldwide. Targeted therapies have emerged as a promising treatment strategy for lung cancers. OBJECTIVE: To evaluate the current landscape of targets and find promising targets for future new drug discovery for lung cancers, this research identified the science-technology-clinical development pattern and mapped the interaction network of targets. METHODS: Targets for cancers were classified into 3 groups based on a paper published in Nature. We searched for scientific pieces of literature, patent documents and clinical trials of targets in Group 1 and Group 2 for lung cancers. Then, a target-target interaction network of Group 1 was constructed, and the science-technology-clinical (S-T-C) development patterns of targets in Group 1 were identified. Finally, based on the cluster distribution and the development pattern of targets in Group 1, interactions between the targets were employed to predict potential targets in Group 2 for drug development. RESULTS: The target-target interaction (TTI) network of group 1 resulted in 3 clusters with different developmental stages. The potential targets in Group 2 are divided into 3 ranks. Level-1 is the first priority and level-3 is the last. Level-1 includes 16 targets, such as STAT3, CRKL, and PTPN11, that are mostly involved in signaling transduction pathways. Level-2 and level-3 contain 8 and 6 targets, respectively, related to various biological functions. CONCLUSION: This study will provide references for drug development in lung cancers, emphasizing that priorities should be given to targets in Level-1, whose mechanisms are worth further exploration.

Long non-coding RNA PART1 predicts a poor prognosis and promotes the malignant progression of pancreatic cancer by sponging miR-122.

BACKGROUND AND OBJECTIVES: Long non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer. METHODS: qRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122. RESULTS: PART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells. CONCLUSIONS: PART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.

Multiomics Integrative Analysis for Discovering the Potential Mechanism of Dioscin against Hyperuricemia Mice.

Hyperuricemia is a well-known key risk factor for gout and can cause a variety of metabolic diseases. Several studies have shown that dioscin could improve metabolic symptoms and reduce the uric acid level in blood. However, there is no comprehensive metabolomic study on the anti-hyperuricemia effects of dioscin. A total of 29 adult male Kunming mice were divided into three groups: Normal (blank), PO (potassium oxonate-administrated, 200 mg/kg/day), and Dioscin (potassium oxonate + dioscin, potassium oxonate 200 mg/kg/day, dioscin 50 mg/kg/day). All mice were treated for 42 days via oral gavage. This paper implemented an untargeted metabolomics study based on 1H NMR and LC-MS to discover the comprehensive mechanism of dioscin. Furthermore, a targeted lipidomics was fulfilled to further analyze the lipid metabolism disorder. Finally, the metabolic pathway mediated by dioscin was verified at the gene level by means of transcriptomics. The results show 53 different metabolites were closely related to the improvement of dioscin in PO-induced hyperuricemia, and 19 of them were lipids. These metabolites are mainly involved in the tricarboxylic acid cycle, lipid metabolism, amino acid metabolism, and pyrimidine metabolism. According to the transcriptomics study, the levels of 89 genes were significantly changed in the PO group compared to the normal control. Among them, six gene levels were restored by the treatment of dioscin. The six changed genes (tx1b, Tsku, Tmem163, Psmc3ip, Tcap, Tbx15) are mainly involved in the cell cycle and energy metabolism. These metabolites and genes might provide useful information for further study of the therapeutic mechanism of dioscin.

Reliability and Validity of the Simplified Chinese Version of the Aberrant Behavior Checklist in Chinese Autism Population.

Background: The Aberrant Behavior Checklist (ABC) is a widely used scale in autism clinical intervention research for the assessment of core symptoms and comorbid emotional and behavioral problems among people with autism. The aim of this study was to examine the psychometric properties of the Simplified Chinese version of the Aberrant Behavior Checklist (SC-ABC) using a sample of people with autism in a Chinese population. Methods: In total, we enrolled 799 patients aged 1.5-33 years old. We collected data using the SC-ABC (n = 799), Autism Behavior Checklist (n = 743), Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) (n = 433) and Achenbach Child Behavior Checklist (CBCL) (n = 319). Eighty-four patients were separately assessed with the SC-ABC by two caregivers simultaneously. Forty-four patients were assessed with the SC-ABC again by same caregiver 2 weeks after the first assessment. SC-ABC data from the whole sample were used for confirmatory factor analysis. We evaluated criterion validity using Spearman's correlation coefficient between scores of the SC-ABC and scores of the Autism Behavior Checklist, ADHD-RS-IV and CBCL separately in the whole sample and different age groups. We calculated the intragroup correlation coefficients and Spearman's correlation coefficient for interrater reliability in 84 samples and test-retest reliability in 44 samples. We conducted Cronbach's α for internal consistency. Results: For the SC-ABC, the intragroup correlation coefficients of five subscales and the total score in interrater and test-retest reliability ranged from 0.87 to 0.92 and from 0.93 to 0.97 (all P < 0.01). The Spearman's correlation coefficient of five subscales and the total score in interrater and test-retest reliability ranged from 0.78 to 0.85 and 0.86 to 0.94, respectively (all P < 0.01). Cronbach's α of five subscales and the total score ranged from 0.75 to 0.96 (all P < 0.01). The Spearman's correlation coefficient for criterion validity for the whole sample and different age groups ranged from 0.39 to 0.76 (all P < 0.01). The model fit for the original five factor model was acceptable, with fit indices of SMR = 0.062 and RMSEA = 0.052. Conclusions: The SC-ABC has satisfactory psychometric properties and can be used in the assessment of core symptoms and comorbid emotional and behavioral problems in patients with autism.

Response to antiepileptic drugs after unsuccessful epilepsy surgery: A multivariate analysis of 103 patients.

OBJECT: Epilepsy patients may still have seizures after surgery, and there have been few studies on the response to antiepileptic drugs (AEDs) after surgery failure. The purpose of this study was to analyze the response to AEDs after unsuccessful epilepsy surgery. METHODS: Patients who underwent unsuccessful epilepsy surgery between January 1999 and January 2019 were evaluated. Patient demographics, etiology, factors related to surgery and AED use patterns were assessed. RESULTS: After excluding the 5 patients who were lost to follow-up and the 2 patients who died, the records of 103 consecutive patients were analyzed. Ninety patients (87.4 %) had seizure recurrence within one year after surgery, 2 (1.9 %) patients had recurrence from one year to two years after surgery, and 11 (10.7 %) patients had recurrence two or more years after surgery (2-10 years). After surgery failure, the patients tried at least 2 kinds of AEDs with different mechanisms for more than 2 years. The average total number of AEDs used was 5.97, the average number of AEDs used before surgery was 3.21, and the average number of AEDs used after surgery was 4.02. After retreatment with AEDs, 10 patients (9.7 %) were seizure-free, 18 patients' (17.5 %) seizures were alleviated, and 75 patients (72.8 %) had seizures as they did prior to the adjustments. The number of AEDs used before and after surgery and the total number of AEDs were not significantly different among the seizure free group, alleviated seizure group and no change group. There were no significant differences in seizure onset age, surgery age, etiology, time between seizure onset and surgery, magnetic resonance imaging, seizure type, localization and lateralization of the surgery site among the three groups. CONCLUSIONS: The results showed that a small percentage of patients (27.2 %) who undergo unsuccessful epilepsy surgery benefit from AED adjustments; however, the vast majority of patients (72.8 %) do not benefit from AED adjustments.

Serum Exosomal Proteins F9 and TSP-1 as Potential Diagnostic Biomarkers for Newly Diagnosed Epilepsy.

Epilepsy is one of the most common chronic neurological diseases in the world, with a high incidence, a high risk of sudden unexplained death, and diagnostic challenges. Exosomes are nanosized extracellular vesicles that are released into physical environments and carry a variety of biological information. Moreover, exosomes can also be synthesized and released from brain cells, passing through the blood-brain barrier, and can be detected in peripheral blood or cerebrospinal fluid. Our study using the tandem mass tag (TMT) approach showed that a total of 76 proteins were differentially expressed in serum exosomes between epilepsy patients and healthy controls, with 6 proteins increasing and 70 proteins decreasing. Analysis of large clinical samples and two mouse models of chronic epilepsy indicated that two significantly differentially expressed serum exosomal proteins, coagulation factor IX (F9) and thrombospondin-1 (TSP-1), represent promising biomarkers for the diagnosis of epilepsy, with area under the curve (AUC) values of up to 0.7776 (95% CI, 0.7306-0.8246) and 0.8534 (95% CI, 0.8152-0.8916), respectively. This is the first study of exosomal proteins in epilepsy, and it suggests that exosomes are promising new tools for the diagnosis of epilepsy.

A Rare KIF1A Missense Mutation Enhances Synaptic Function and Increases Seizure Activity.

Although genetic factors are considered a main etiology of epilepsy, the causes of genetic epilepsy in the majority of epilepsy patients remain unknown. Kinesin family member 1A (KIF1A), a neuron-specific motor protein that moves along with microtubules, is responsible for the transport of membranous organelles and synaptic vesicles. Variants of KIF1A have recently been associated with hereditary spastic paraplegia (HSP), hereditary sensory and autonomic neuropathy type 2 (HSANII), and intellectual disability. However, mutations in KIF1A have not been detected in patients with epilepsy. In our study, we conducted customized sequencing of epilepsy-related genes of a family with six patients with generalized epilepsy over three generations and identified a rare heterozygous mutation (c.1190C > A, p. Ala397Asp) in KIF1A. Whole-cell recordings from primary cultured neurons revealed that the mutant KIF1A increases the excitatory synaptic transmission but not the intrinsic excitability of neurons, and phenotype testing in zebrafish showed that this rare mutation results in epileptic seizure-like activity. These results provide new evidence demonstrating that KIF1A dysfunction is involved in epileptogenesis.