Comprehensive evaluation methods for translating BCI into practical applications: usability, user satisfaction and usage of online BCI systems.

Although brain-computer interface (BCI) is considered a revolutionary advancement in human-computer interaction and has achieved significant progress, a considerable gap remains between the current technological capabilities and their practical applications. To promote the translation of BCI into practical applications, the gold standard for online evaluation for classification algorithms of BCI has been proposed in some studies. However, few studies have proposed a more comprehensive evaluation method for the entire online BCI system, and it has not yet received sufficient attention from the BCI research and development community. Therefore, the qualitative leap from analyzing and modeling for offline BCI data to the construction of online BCI systems and optimizing their performance is elaborated, and then user-centred is emphasized, and then the comprehensive evaluation methods for translating BCI into practical applications are detailed and reviewed in the article, including the evaluation of the usability (including effectiveness and efficiency of systems), the evaluation of the user satisfaction (including BCI-related aspects, etc.), and the evaluation of the usage (including the match between the system and user, etc.) of online BCI systems. Finally, the challenges faced in the evaluation of the usability and user satisfaction of online BCI systems, the efficacy of online BCI systems, and the integration of BCI and artificial intelligence (AI) and/or virtual reality (VR) and other technologies to enhance the intelligence and user experience of the system are discussed. It is expected that the evaluation methods for online BCI systems elaborated in this review will promote the translation of BCI into practical applications.

The impact of different contrast agent concentrations on excimer laser ablation:an in vitro study / 中国介入心脏病学杂志

Objective To explore the impact of contrast agent concentration on the excimer laser's effect on plaque ablation.Methods Using a laser catheter with a diameter of 0.9 mm,we conducted plaque model ablation experiments employing a 308-nanometer xenon chloride excimer laser.During the excimer laser ablation process,five groups were formed based on the injected contrast agent concentrations:a saline group,25%concentration group,50%concentration group,75%concentration group,and 100%concentration group.Optical coherence tomography was utilized to assess the changes in plaque lumen area after excimer laser ablation,evaluating the impact of contrast agent concentration on the excimer laser's ablation efficacy.Simultaneously,a water manometer was used to measure the shockwave pressure generated by the excimer laser in liquids with different contrast agent concentrations,aiming to explore the correlation between the shockwave pressure of the excimer laser and its ablative effect.Results The ablation areas in the 75%concentration group and the 100%concentration group were similar(P＞0.05),both exceeding those in the 50%concentration contrast agent group,25%concentration group,and saline group(all P＜0.001).Specifically,the ablation area in the 50%concentration group was significantly larger than that in the 25%concentration group and saline group(both P＜0.001),while the 25%concentration group was larger than the saline group(P＜0.001).The influence of contrast agent concentration on the shockwave pressure of the excimer laser exhibited a similar trend.Additionally,there was a significant positive correlation between the shockwave pressure generated by the excimer laser and its ablation area(r=0.9987,P＜0.001).Conclusions The intensity of excimer laser ablation on plaque tissue can be modulated by altering the contrast agent concentration.These findings offer guidance for the application of excimer laser in conjunction with contrast agent injection techniques in the treatment of coronary artery disease.

Efficacy on the Acute Lumen Gain Post Excimer Laser Combined With Drug-coated Balloon for Instent Restenosis and the Relationship With Different Neointimal Tissues Defined by Optical Coherence Tomography / 中国循环杂志

Objectives:To compare the efficacy of the combination of excimer laser coronary angioplasty(ELCA)and drug-coated balloon(DCB)for in-stent restenosis(ISR)and to evaluate the impact of neointimal tissue characteristics on treatment outcomes. Methods:A total of 96 ISR lesions from 86 patients who underwent optical coherence tomography(OCT)evaluation and DCB with or without ELCA treatment at The First Medical Center of Chinese PLA General Hospital from January 2019 to May 2023 were retrospectively analyzed.ISR lesions were divided into ELCA+DCB group(n=30)and DCB group(n=66).Additionally,ISR lesions were classified as homogeneous and non-heterogeneous patterns based on the OCT characteristics of the neointimal tissue,and the impact on acute lumen gains was compared between different ISR patterns.Acute lumen gain(ΔMLA)was defined as the changes in minimum lumen area before and after the intervention. Results:The ELCA+DCB group had a significantly greater ΔMLA than the DCB group([3.2±0.8]mm2 vs.[2.6±1.4]mm2,P=0.015).Among the ISR with a homogeneous pattern,the ΔMLA of the ELCA+DCB group was significantly greater than that of the DCB group([3.0±0.9]mm2 vs.[2.2±1.1]mm2,P=0.030).There was no significant difference in ΔMLA between the two ISR groups with the non-homogeneous pattern([3.4±0.7]mm2 vs.[3.2±1.5]mm2,P=0.533).There was no death,the rate of target lesion revascularization was similar between the patients with lesions receiving DCB treatment and patients receiving ELCA +DCB treatment(7.4%vs.4.2%,P＞0.05). Conclusions:The combination of ELCA and DCB is an effective strategy for treating ISR,which can achieve greater acute lumen gain compared to DCB treatment alone,especially for the treatment of homogenous ISR pattern characterized by OCT.

Development and accuracy verification of a continuous non-invasive blood pressure measurement device/ / 中国医学装备

Objective:To develop a continuous non-invasive blood pressure measurement device(NC-BPM)and verify the accuracy of that in monitoring blood pressure.Methods:A NC-BPM type of non-invasively continuous blood pressure measurement device(NC-BPM for short)was developed.The entire system consisted of four modules included one sensor which shape was finger cot,one unit of signal acquisition and pressure control,one calibration system for height and one host.The Omron J760 electronic sphygmomanometer(J760)and the CNAP Monitor500 continuous non-invasive blood pressure monitoring system(CNAP Monitor500)were used as the reference sphygmomanometer of verifying accuracy of the monitored blood pressure.The blood pressures of 25 subjects at three stages included static stage,blood pressure change stage and stage post calibration were respectively measured according to the standard test procedure of wearable sleeveless blood pressure measurement device of Institute of Electrical and Electronics Engineers(IEEE).Results:Both NC-BPM and CNAP Monitor500 collected 13753 data points,and there were high correlation in systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean blood pressure(MAP)between the two devices(r=0.96,0.97,0.98,P<0.05).A total of 379 data points were collected by Omron J760,and there were high correlation in SBP and DBP between NC-BPM and Omron J760(r=0.98,0.95,P<0.05).According to the standards of British Hypertension Society(BHS)and the American Association for the Advancement of Medical Instrumentation(AAMI)to conduct grade evaluation,and the proportions of the SBP differences between NC-BPM and CNAP Monitor500 within the ranges of 0～5 mmHg,0～10 mmHg and 0～15 mmHg were respectively 85.01%,97.60%and 99.47%,and the proportions of the DBP differences between them within the three ranges were respectively 84.34%,99.85%and 100%,and the proportions of the MAP differences were respectively 92.66%,99.72%and 99.96%,all of which belonged to BHS grade A.The pressure difference values of measured SBP,DBP and MAP between the two devices were respectively(0.67±5.07)mmHg,(2.43±2.87)mmHg and(1.43±2.89)mmHg,which were within the(5±8)mmHg of AAMI standard range.The proportions of the SBP differences between NC-BPM and Omron J76 within the ranges of 0～5 mmHg,0～10 mmHg and 0～15 mmHg were respectively 79.95%,97.36%and 100%,and the proportions of the DBP differences between them within the three ranges were respectively 89.71%,99.74%and 100%,all of which belonged to BHS grade A.The difference values of systolic and diastolic blood pressures of brachial artery between the two devices were respectively(1.57±4.18)mmHg and(0.57±5.20)mmHg,which were within the(5±8)mmHg of AAMI standard range.Conclusion:The NC-BPM device has passed the first stage of clinical trials in accordance with IEEE standards,which can proceed to the next stage of clinical verification trials.

Mechanistic Study of Icaritin-Induced Inactivation of Cytochrome P450 2C9.

Icaritin (ICT) is a prenylflavonoid derivative that has been approved by National Medical Products Administration for the treatment of hepatocellular carcinoma. This study aims to evaluate the potential inhibitory effect of ICT against cytochrome P450 (CYP) enzymes and to elucidate the inactivation mechanisms. Results showed that ICT inactivated CYP2C9 in a time-, concentration-, and NADPH-dependent manner with Ki = 1.896 µM, Kinact = 0.02298 minutes-1, and Kinact/Ki = 12 minutes-1 mM-1, whereas the activities of other CYP isozymes was minimally affected. Additionally, the presence of CYP2C9 competitive inhibitor, sulfaphenazole, superoxide dismutase/catalase system, and GSH all protected CYP2C9 from ICT-induced activity loss. Moreover, the activity loss was neither recovered by washing the ICT-CYP2C9 preincubation mixture nor the addition of potassium ferricyanide. These results, collectively, implied the underlying inactivation mechanism involved the covalent binding of ICT to the apoprotein and/or the prosthetic heme of CYP2C9. Furthermore, an ICT-quinone methide (QM)-derived GSH adduct was identified, and human glutathione S-transferases (GST) isozymes GSTA1-1, GSTM1-1, and GSTP1-1 were shown to be substantially involved in the detoxification of ICT-QM. Interestingly, our systematic molecular modeling work predicted that ICT-QM was covalently bound to C216, a cysteine residue located in the F-G loop downstream of substrate recognition site (SRS) 2 in CYP2C9. The sequential molecular dynamics simulation confirmed the binding to C216 induced a conformational change in the active catalytic center of CYP2C9. Lastly, the potential risks of clinical drug-drug interactions triggered by ICT as a perpetrator were extrapolated. In summary, this work confirmed that ICT was an inactivator of CYP2C9. SIGNIFICANCE STATEMENT: This study is the first to report the time-dependent inhibition of CYP2C9 by icaritin (ICT) and the intrinsic molecular mechanism behind it. Experimental data indicated that the inactivation was via irreversible covalent binding of ICT-quinone methide to CYP2C9, while molecular modeling analysis provided additional evidence by predicting C216 as the key binding site which influenced the structural confirmation of CYP2C9's catalytic center. These findings suggest the potential of drug-drug interactions when ICT is co-administered with CYP2C9 substrates clinically.

Characterization of the anti-fatigue effect of Astragali Radix from the Shanxi Hengshan area and its association with taurine metabolism based on 1H NMR metabolomic technology combined with network pharmacology / 药学学报

The objective of this work was to evaluate the anti-fatigue efficacy of Astragali Radix (AR) from the Shanxi Hengshan area and to reveal possible mechanisms by which it relieves fatigue. Efficacy differences between Guangling (GL) and Hunyuan (HY) AR preparations were compared and evaluated, and an 1H NMR metabolomic technique combined with statistical methods was used to identify the metabolites in different groups of mouse gastrocnemius muscle tissues. The differential metabolites after AR treatments were identified according to VIP and P values and the upstream targets were predicted with the help of Metscape. Cytoscape software was utilized to construct a network map of AR potential anti-fatigue targets. Key differential metabolites were identified based on shared targets and entered into the Metaboanalyst website for pathway enrichment analysis, which led to the preliminary elucidation of the molecular mechanisms. The results showed that intervention with AR can significantly improve the swimming-to-exhaustion time, increase liver glycogen, and reduce urea-nitrogen levels in mice. The difference between GL and HY ARs was relatively small, indicating that the quality of AR produced in the Hengshan area is consistent and stable. The metabolic fingerprints of mouse gastrocnemius muscle tissue extracts were composed of 34 metabolites, and the statistical results showed that 19 differential metabolites were significantly reversed after the Hengshan AR intervention. We found that the anti-fatigue effects of AR in the Shanxi Hengshan area were mainly associated with taurine and hypotaurine metabolism through regulation of GAD1, based on network pharmacological analysis. In conclusion, 1H NMR metabolomic techniques were combined with network pharmacology to compare and evaluate the quality of Hengshan ARs, and further associate the fatigue relieve with the regulation of taurine metabolism. This provides a theoretical basis for the resource utilization of Hengshan ARs and the development of anti-fatigue-related products. The animal experiments in this study followed the regulations of the Animal Ethics Committee of Shanxi University and passed the ethical review of animal experiments (Approval No. SXULL2021028).

Feasibility and safety of excimer laser coronary angioplasty combined with drug-coated balloon for recurrent in-stent restenosis patients / 中国介入心脏病学杂志

Objective To explore the safety and efficacy of combining excimer laser coronary angioplasty with drug-coated balloon in the treatment of recurrent in-stent restenosis(R-ISR).Methods Clinical data from a cohort of 27 patients with a total of 30 R-ISR lesions,who underwent treatment with combined excimer laser coronary angioplasty and drug-coated balloons at our hospital from October 2019 to April 2023,were retrospectively analyzed.Patient baseline information,coronary angiography results,procedural details,and in-hospital complications were collected.Follow-up assessments were conducted at 1,3,and 6 months post-intervention to document major clinical events.Results A total of 27 patients[mean age(66.4±9.8)years]with 30 lesions(100％)achieved procedural and treatment success.There were no cases of acute myocardial infarction,coronary perforation,cardiac tamponade,urgent target lesion revascularization,or death during hospitalization.After 6 months of follow-up,there were no occurrences of acute myocardial infarction or death.Two patients(with a total of two lesions)underwent target lesion revascularization,one patient received repeated drug-balloon dilatation,and one patient underwent coronary artery bypass grafting.Conclusions Excimer laser coronary angioplasty combined with drug-coated balloons is a safe and effective treatment strategy for recurrent in-stent stenosis,but further studies are needed for confirmation.

Effect of remote ischemic preconditioning combined with postconditioning on postoperative delirium in patients undergoing cardiac valve replacement under cardiopulmonary bypass / 中华胸心血管外科杂志

Objective:To investigate the effect of remote ischemic preconditioning combined with postconditioning (RIPC+ RIPostC) on postoperative delirium (POD) in patients undergoing cardiac valve replacement under cardiopulmonary bypass (CPB).Methods:Eighty patients aged 44-64 years old and scheduled to elective heart valve replacement under CPB in the operating room of our hospital were recruited and divided into control group (group C) and group R according to random number table method, with 40 cases in each group. Patients in group R underwent RIPC 30 minutes before the start of CPB and RIPostC 30 minutes before the end of CPB. The specific treatment measures were as follows: tie an inflatable cuff on the patient' s lower limb, inflate and pressurize until the pressure to 200 mmHg, hold for 5 minutes, and then completely deflate the cuff until the pressure to 0; after 5 minutes, inflate and pressurize again, and repeat for 3 cycles. The cuff was tied to the patient' s lower limb, but no inflation and deflation were performed in group C. Peripheral venous blood was drawn 1 day before operation and 1 day and 3 days after operation, and blood routine was determined. POD was assessed by the intensive care unit (ICU) consciousness disturbance assessment method (CAM-ICU) within 3 days after the operation. Neurocognitive testing was performed preoperatively, at discharge, and 3 months postoperatively, and postoperative cognitive dysfunction (POCD) and dementia (AD) were assessed using the Mini-Mental State Examination Scale (MMSE), with exclusion of preoperative patients with <24 points. Intraoperative and postoperative adverse events including sinus bradycardia or hypotension/hypertension, postoperative infection, etc. were recorded. The length of hospital stay and 90-day mortality were recorded. After 3 months, data related to sleep, quality of life, anxiety and pain were collected using questionnaires.Results:The white blood cell count, neutrophil count and percentage of neutrophils in the two groups at 1 day and 3 days after operation were all higher than those at 1 day before operation, but the indexes in group R was significantly lower than those in group C ( P<0.05). A total of 13 patients (32.5%) in group C developed POD within 3 days after surgery, while 27 patients (67.5%) did not develop POD, and there was a significant difference between the groups ( P<0.05). A total of 5 patients (12.5%) in group R developed POD within 3 days after surgery, and 35 patients (87.5%) did not develop POD. At the 90-day follow-up, there was no difference in the MMSE score compared with the baseline ( P>0.05). A total of 4 patients (10%) developed neurocognitive dysfunction after surgery. There was no difference in the incidence of POCD between the two groups ( P>0.05). The incidence of adverse events such as bradykinesia, hypotension/hypertension, and postoperative infection were similar between the two groups, and there was no significant difference ( P>0.05). During the 90-day follow-up period after surgery, no patient died in either group. There was no significant difference in postoperative hospital stay between the two groups ( P>0.05). Using the EQ-5D questionnaire to evaluate the quality of life of the two groups of patients, the results showed that there was no statistically significant difference between the two groups ( P>0.05). At 3 months after operation, there was no significant difference in sleep quality between the two groups ( P>0.05). Conclusion:RIPC+ RIPostC can reduce the inflammatory response, reduce the incidence of POD and improve the quality of life after operation in patients with heart valve replacement under CPB.

MiR-181a promotes the growth of chondrosarcoma cells by targeting PTEN / 中国医师杂志

Objective:To explore the effect of miR-181a on chondrosarcoma cell growth through phosphatase and tensin homolog(PTEN) and its possible regulatory mechanism.Methods:From January to December 2022, 10 fresh chondrosarcoma and 10 chondroma tissues from orthopedic patients of Hunan Provincial People′s Hospital were collected, and the expression of miR-181a in chondrosarcoma and chondroma tissues was detected using real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); Chondrosarcoma cell SW1353 was cultured in vitro and transfected with miR-181a inhibitor (miR-181a inhibition group) and control (miR-NC, control group), respectively. The effects of miR-181a on the growth and proliferation of SW1353 cells were detected by cell counting kit (CCK-8) and clone formation test, respectively; The binding sites between miR-181a and PTEN were predicted through the Target Scan database, and verified using dual luciferase reporter gene experiments; The mimetic miR-181a (miR-181a group) and its control (miR-NC, control group) were transfected into chondrosarcoma cell SW1353, respectively. The adenosine triphosphate (ATP) content, glucose consumption, and lactic acid production in the cells were measured, and the effect of miR-181a on glycolysis of SW1353 cells was analyzed. Results:The expression of miR-181a in chondrosarcoma tissues was significantly higher than that in chondroma tissues ( P<0.05). The cell growth and clonogenesis ability of miR-181a inhibition group were significantly lower than those of control group (all P<0.05). It was predicted by Target Scan online website that there might be binding sites between miR-181a and PTEN, and co-transfection of wild-type PTEN and miR-181a could significantly reduce luciferase activity by double luciferase reporter assay ( P<0.05). The ATP content, glucose consumption and lactic acid production of miR-181a group were significantly higher than those of miR-NC group (all P<0.05). Conclusions:MiR-181a promotes the growth of chondrosarcoma cells through PTEN-mediated glycolysis.

Cardiac rehabilitation program for patients undergoing small incision aortic valve replacement / 中华胸心血管外科杂志

Objective:To study the effect of cardiac rehabilitation program on recovery of patients after small incision aortic valve replacement.Methods:600 patients who underwent small incision aortic valve replacement in our hospital from January 2015 to January 2020 were retrospectively collected and divided into Cardiac rehabilitation group(CR) and control group by propensity matching analysis. Clinical data of CR group and control group were collected 6 months and 12 months after the beginning of Cardiac rehabilitation program. The primary outcome measures were the peak oxygen uptake(VO 2 Peak) of cardiopulmonary function test and the number of patients attending cardiovascular specialty in tertiary hospitals after the rehabilitation program began. The secondary outcome measures were 6-minute Walk test(6-MWT), psychological evaluation, and assessment of cardiovascular disease risk factors. Results:After 6 months and 12 months of cardiac rehabilitation program, the VO2 peak in CR group was statistically significant compared with the control group, and the 6-MWT index after 12 months was statistically significant.The cardiovascular specialist visits in tertiary hospitals in the two groups were statistically significant. The comparison of psychological self-rating scale and cardiovascular disease risk factors between the two groups was statistically significant after propensity matching analysis.Conclusion:Cardiac rehabilitation has a positive effect on postoperative recovery after small incision aortic valve replacement, and can improve patients’ motor ability.

First Detection of Mukawa Virus in Ixodes persulcatus and Haemaphysalis concinna in China.

Mukawa virus (MKWV), a novel tick-borne virus (TBV) of the genus Phlebovirus of family Phenuiviridae, has been firstly reported in Ixodes persulcatus in Japan. In this study, we made an epidemiological investigation in China to obtain the geographic distribution and genetic features of this virus outside Japan. We screened 1,815 adult ticks (665 I. persulcatus, 336 Dermacentor silvarum, 599 Haemaphysalis longicornis, 170 Rhipicephalus microplus, 45 Haemaphysalis concinna) and 805 wild small mammals collected from eight provinces. The positive rate of 6.77% (45/665, including 18 female and 27 male I. persulcatus) and 2.22% (1/45, 1 male H. concinna) were obtained from I. persulcatus and H. concinna in Heilongjiang province, respectively. No evidence of MKWV infection was found in other three tick species or any of the mammalian species. The virus can infect the Vero cells successfully, indicating the ability of MKWV to replicate in mammalian cells. A phylogenetic tree based on the nucleotide sequences of L, M, and S segments demonstrated that the Japanese MKWV variant, our two MKWV variants, and KURV were clustered with the members of the mosquito/sandfly-borne phleboviruses and distant from other tick-borne phenuiviruses. A phylogenetic analysis based on 895 bp partial L gene sequences (n = 46) showed that all MKWV sequences were separated into three lineages. Our results showed the presence of MKWV in I. persulcatus and H. concinna in northeast of China, highlighting the necessity of epidemiological study in wider regions. Due to the ability of MKWV to replicate in mammalian cells, the potential for zoonosis, and wide distribution of I. persulcatus and H. concinna in China, the important vectors of MKWV, further screening to more tick species, wild animals, domestic animals, and humans raises up practical significance.

Pig carcass-derived biochar caused contradictory effects on arsenic mobilization in a contaminated paddy soil under fluctuating controlled redox conditions.

Contamination of paddy soils by arsenic (As) is of great concern for human health and the environment. The impact of animal-derived biochar on As mobilization under fluctuating redox conditions in paddy soils has not been studied. Consequently, we investigated the effects of pig carcass-derived biochar (PB) on As (im)mobilization in a contaminated paddy soil under controlled redox potential (Eh) using a biogeochemical microcosm-setup. The addition of PB decreased the concentration of dissolved As at Eh = +100 and +200 mV by 38.7% and 35.4%, respectively (compared to the control), because of the co-precipitation of As with Fe-Mn oxides and the complexation between As and aromatic organic molecules. However, under reducing conditions (Eh = -300 mV), PB increased the dissolved As by 13.5% through promoting reduction and decomposition of As-bearing Fe minerals (e.g., ferrihydrite-As, Fe-humic-As). Under oxidizing conditions (Eh = +250 mV), PB increased the dissolved As by 317.6%, due to the associated increase of pH. We conclude that As mobilization in PB-treated paddy soils is highly affected by Eh. PB can be used to reduce the environmental risk of As under moderately reducing conditions, but it may increase the risk under highly reducing and oxidizing conditions in paddy soils.

Meta analysis of indocyanine green fluorescence imaging guided laparoscopic liver tumor resection / 中华肝胆外科杂志

Objective:This meta-analysis was conducted to systematically evaluate the short-term efficacy and safety of indocyanine green fluorescence imaging guided laparoscopic liver tumor resection (FIGLTR).Methods:A systematic search was made for the literature on indocyanine green fluorescence image-guided laparoscopic hepatectomy in randomized, semi-randomized controlled trials and observational studies, and manually search published materials and conference papers in Chinese and English and trace references included in the literature. The retrieval period was up to September 2021. The quality of included studies was evaluated, then the meta-analysis was conducted using Review Manager 5.1 software.Results:Ten studies were included with 803 patients, including 341 in the FIGLTR group and 462 in the non-FIGLTR group. Meta results showed that: Compared to the traditional resection group, indocyanine green fluorescence imaging can significantly shorten the operative time ( MD=-22.61, 95% CI: -34.20--11.03, P<0.001), reduce intraoperative bleeding ( MD=-49.17, 95% CI: -84.99--13.36, P<0.01), shorter hospital stay ( MD=-0.89, 95% CI: -7.72--0.06, P<0.05), Improve the removal rate of R 0 edge ( OR=8.80, 95% CI: 1.96-39.44, P<0.05) and reduce the incidence of postoperative complications ( OR=0.55, 95% CI: 0.34-0.87, P<0.05) of laparoscopic liver tumor resection. There were no differences found in portal block time and transfusion rate. Conclusion:Indocyanine green fluorescence imaging technology provides a new way for safe and accurate laparoscopic resection of liver tumors.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Recent advance in ubiquitin-proteasome system and TAR DNA/RNA-binding domain protein-43 in treatment of Alzheimer's disease / 中华神经医学杂志

TAR DNA/RNA-binding domain protein 43 (TDP-43) has become one of the pathogenic factors of many neurodegenerative diseases, such as Alzheimer's disease (AD). Clearance of abnormal accumulation of TDP-43 might be the potential treatment target in AD patients. Ubiquitin-proteasome system (UPS) is one of the main ways of protein clearance. UPS dysfunction plays an important role in the pathogenesis and progression of AD. This review focuses on the roles of TDP-43 and UPS in the pathogenesis of AD, as well as the research progress of UPS mediated clearance TDP-43 in the treatment of AD.

Infection with severe fever with thrombocytopenia virus in healthy population: a cohort study in a high endemic region, China.

BACKGROUND: Severe fever with thrombocytopenia (SFTS) caused by SFTS virus (SFTSV) was a tick-borne hemorrhagic fever that posed significant threat to human health in Eastern Asia. The study was designed to measure the seroprevalence of SFTSV antibody in healthy population residing in a high endemic region. METHODS: A cohort study was performed on healthy residents in Shangcheng County in Xinyang City from April to December in 2018, where the highest SFTS incidence in China was reported. Anti-SFTSV IgG was measured by indirect enzyme-linked immunosorbent assay and neutralizing antibody (NAb) was detected by using PRNT50. The logistic regression models were performed to analyze the variables that were associated with seropositive rates. RESULTS: Totally 886 individuals were recruited. The baseline seroprevalence that was tested before the epidemic season was 11.9% (70/587) for IgG and 6.8% (40/587) for NAb, which was increased to 13.4% (47/350) and 7.7% (27/350) during the epidemic season, and further to 15.8% (80/508) and 9.8% (50/508) post epidemic. The IgG antibody-based seropositivity was significantly related to the patients aged ≥ 70 years old [adjusted odds ratio (OR) = 2.440, 95% confidence interval (CI): 1.334-4.461 compared to the group of < 50 years old, P = 0.004], recent contact with cats (adjusted OR = 2.195, 95% CI: 1.261-3.818, P = 0.005), and working in tea garden (adjusted OR = 1.698, 95% CI: 1.002-2.880, P = 0.049) by applying multivariate logistic regression model. The NAb based seropositivity was similarly related to the patients aged ≥ 70 years old (adjusted OR = 2.691, 95% CI: 1.271-5.695 compared to the group of < 50 years old, P = 0.010), and recent contact with cats (OR = 2.648, 95% CI: 1.419-4.941, P = 0.002). For a cohort of individuals continually sampled with 1-year apart, the anti-SFTSV IgG were maintained at a stable level, while the NAb level reduced. CONCLUSIONS: Subclinical infection might not provide adequate immunity to protect reinfection of SFTSV, thus highlighting the ongoing threats of SFTS in endemic regions, which called for an imperative need for vaccine development. Identification of risk factors might help to target high-risk population for public health education and vaccination in the future.

The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China.

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34-0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23-4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It's concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

Prognostic Value of Immune-Related Multi-IncRNA Signatures Associated With Tumor Microenvironment in Esophageal Cancer.

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Hence, for a better understanding of tumor microenvironment and to seek for novel molecular targets for esophageal cancer, we performed related studies on two histopathological subtypes of esophageal cancer: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Bioinformatic analyses were conducted based on the RNA-seq, genomic mutation, and clinical data from TCGA and GEO cohorts. We clustered patients into high-immunity and low-immunity groups through the ssGSEA results. The ESTIMATE algorithm was used to evaluate the tumor microenvironment. Patients with high immunity in both ESCC and EAC had lower tumor purity and poor survival. Subsequently, CIBERSORT was performed to learn about the detailed difference of tumor-infiltrating lymphocytes (TILs) between high- and low-immunity patients. Specific increase of M2 macrophages and decrease of activated dendric cells can be observed in ESCC and EAC, respectively. The most enriched functions and pathways of high-immunity patients were immunoglobulin complex, MHC class II protein complex, and allograft rejection according to the GO terms and KEGG. Two prognostic immune-related multi-lncRNA risk models were constructed and validated by ROC curve and PCA in ESCC and EAC. High-risk patients in both subtypes had poor survival, advanced clinical characteristics, and higher drug susceptibility except cisplatin and sorafenib. In addition, the tumor mutation burden (TMB) was positively correlated with the risk level in the ESCC and EAC and showed distinct differences between the two subtypes. In summary, we comprehensively analyzed the tumor microenvironment for two subtypes of esophageal cancer, identified two multi-lncRNA signatures predictive for the prognosis, and explored the possibility of the signatures to forecast drug susceptibility as well as TMB for the first time. The findings may serve as a conceptual basis for innovative strategy of individualized immunotherapy for esophageal cancer.

Role of the miR-133a-5p/FBXO6 axis in the regulation of intervertebral disc degeneration.

OBJECTIVE: Low back pain is a leading cause of disabilities worldwide, and intervertebral disc degeneration (IVDD)-related disorders have been recognised as one of the main contributors. Nevertheless, the underlying mechanism has not yet been fully understood. The aim of this study was to investigate the role of the miR-133a-5p/FBXO6 axis in the regulation of IVDD. METHODS: RT-qPCR, WB and IHC were performed to assess the expression of FBXO6 in human IVD tissues. Nucleus pulposus (NP) cells were treated with IL-1ß to induce IVDD cellular model. Silence of FBXO6 was achieved using specific siRNAs. CCK-8 assay, flow cytometry, TUNEL assay, RT-qPCR and WB were used to evaluate the role and mechanism of FBXO6 in the process of IVDD. Online tools, GSE datasets and RT-qPCR were used to search the candidate miRNAs targeting FBXO6. The direct binding sites between FBXO6 and miR-133a-5p were further verified by a dual luciferase assay. RT-qPCR, WB and rescue experiments were conducted to identify the regulatory function of miR-133a-5p on the expression of aggrecan, collagen Ⅱ, MMP3, ADAMTS5, IL-6 and COX2. In addition, the role of the NF-κB pathway in regulating miR-133a-5p was studied using lentiviral shRNA, WB and RT-qPCR. RESULTS: Results showed that FBXO6 mainly expressed in the NP tissue of IVD and the expression of FBXO6 decreased with the process of IVDD as well as under IL-1ß stimulation. The silence of FBXO6 led to the decreased expression of aggrecan and collagen Ⅱ and the increased expression of MMP3, ADAMTS5, IL-6 and COX2, which further induced the degeneration of NP cells. The bioinformatic analysis showed that miR-133a-5p was the candidate miRNA targeting FBXO6. miR-133a-5p was upregulated in IVDD tissues and significantly inhibited the expression of FBXO6. The inhibition of miR-133a-5p ameliorated the acceleration of IVDD induced by the silence of FBXO6 in vitro. Moreover, it was demonstrated that IL-1ß regulated the expression of the miR-133a-5p/FBXO6 axis via the NF-κB pathway in NP cells. CONCLUSION: miR-133a-5p was upregulated by IL-1ß to aggravate intervertebral disc degeneration via sponging FBXO6. Inhibiting miR-133a-5p expression or rescuing FBXO6 expression may be promising strategies for the treatment of IVDD. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study suggests that the miR-133a-5p/FBXO6 axis could regulate NP cells proliferation, apoptosis, synthesis and degradation of extracellular matrix, which provides a promising therapeutic target and strategy for the treatment of IVDD.