General anesthetic agents induce neurotoxicity through astrocytes

Neuroscientists have recognized the importance of astrocytes in regulating neurological function and their influence on the release of glial transmitters.Few studies,however,have focused on the effects of general anesthetic agents on neuroglia or astrocytes.Astrocytes can also be an important target of general anesthetic agents as they exert not only sedative,analgesic,and amnesic effects but also mediate general anesthetic-induced neurotoxicity and postoperative cognitive dysfunction.Here,we analyzed recent advances in understanding the mechanism of general anesthetic agents on astrocytes,and found that exposure to general anesthetic agents will destroy the morphology and proliferation of astrocytes,in addition to acting on the receptors on their surface,which not only affect Ca^(2+)signaling,inhibit the release of brain-derived neurotrophic factor and lactate from astrocytes,but are even involved in the regulation of the pro-and anti-inflammatory processes of astrocytes.These would obviously affect the communication between astrocytes as well as between astrocytes and neighboring neurons,other neuroglia,and vascular cells.In this review,we summarize how general anesthetic agents act on neurons via astrocytes,and explore potential mechanisms of action of general anesthetic agents on the nervous system.We hope that this review will provide a new direction for mitigating the neurotoxicity of general anesthetic agents.

Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease:Mechanism,clinical evidence,and prospect

The population of non-alcoholic fatty liver disease(NAFLD)patients along with relevant advanced liver disease is projected to continue growing,because currently no medications are approved for treatment.Fecal microbiota transplantation(FMT)is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease.There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment,however,existing findings diverge on its effects.Herein,we briefly summarized the mechanism of FMT for NAFLD treatment,reviewed randomized controlled trials for evaluating its efficacy in NAFLD,and proposed the prospect of future trials on FMT.

Mirizzi syndrome:Problems and strategies

Mirizzi syndrome is a serious complication of gallstone disease.It is caused by the impacted stones in the gallbladder neck or cystic duct.One of the features of Mirizzi syndrome is severe inflammation or dense fibrosis at the Calot’s triangle.In our clinical practice,bile duct,branches of right hepatic artery and right portal vein clinging to gallbladder infundibulum are often observed due to gallbladder infundibulum adhered to right hepatic hilum.The intraoperative damage of branches of right hepatic artery occurs more easily than that of bile duct,all of which are hidden pitfalls for surgeons.Magnetic resonance cholangiopancreatography(MRCP)and endoscopic retrograde cholangiopancreatography(ERCP)are the preferable tools for the diagnosis of Mirizzi syndrome.Anterograde cholecystectomy in Mirizzi syndrome is easy to damage branches of right hepatic artery and bile duct due to gallbladder infundibulum adhered to right hepatic hilum.Subtotal cholecystectomy is an easy,safe and definitive approach to Mirizzi syndrome.When combined with the application of ERCP,a laparoscopic management of Mirizzi syndrome by well-trained surgeons is feasible and safe.The objective of this review was to highlight its existing problems:(1)low preoperative diagnostic rate,(2)easy to damage bile duct and branches of right hepatic artery,and(3)high concomitant gallbladder carcinoma.Meanwhile,the review aimed to discuss the possible therapeutic strategies:(1)to enhance its preoperative recognition by imaging findings,and(2)to avoid potential pitfalls during surgery.

Compression and stretching of ring vortex in a bulk nonlinear medium

We explore the nonlinear gain coupled Schrödinger system through the utilization of the variables separation method and ansatz technique.By employing these approaches,we generate hierarchies of explicit dissipative vector vortices(DVVs)that possess diverse vorticity values.Numerous fundamental characteristics of the DVVs are examined,encompassing amplitude profiles,energy fluxes,parameter effects,as well as linear and dynamic stability.

3D Road Network Modeling and Road Structure Recognition in Internet of Vehicles

Internet of Vehicles (IoV) is a new system that enables individual vehicles to connect with nearby vehicles,people, transportation infrastructure, and networks, thereby realizing amore intelligent and efficient transportationsystem. The movement of vehicles and the three-dimensional (3D) nature of the road network cause the topologicalstructure of IoV to have the high space and time complexity.Network modeling and structure recognition for 3Droads can benefit the description of topological changes for IoV. This paper proposes a 3Dgeneral roadmodel basedon discrete points of roads obtained from GIS. First, the constraints imposed by 3D roads on moving vehicles areanalyzed. Then the effects of road curvature radius (Ra), longitudinal slope (Slo), and length (Len) on speed andacceleration are studied. Finally, a general 3D road network model based on road section features is established.This paper also presents intersection and road section recognition methods based on the structural features ofthe 3D road network model and the road features. Real GIS data from a specific region of Beijing is adopted tocreate the simulation scenario, and the simulation results validate the general 3D road network model and therecognitionmethod. Therefore, thiswork makes contributions to the field of intelligent transportation by providinga comprehensive approach tomodeling the 3Droad network and its topological changes in achieving efficient trafficflowand improved road safety.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor prognosis.Previous studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is lacking.AIM To investigate the causal relationship between gut microbiota and CCA risk.METHODS We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA.Genetic variants were used as instrumental variables.Multiple sensitivity analyses assessed result robustness.RESULTS Fifteen gut microbial taxa showed significant causal associations with CCA risk.Higher genetically predicted abundance of genus Eubacteriumnodatum group,genus Ruminococcustorques group,genus Coprococcus,genus Dorea,and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA.Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae,genus Alistipes,order Enterobacteriales,and phylum Firmicutes.Protective effects against CCA were suggested for genus Collinsella,genus Eisenbergiella,genus Anaerostipes,genus Paraprevotella,genus Parasutterella,and phylum Verrucomicrobia.Sensitivity analyses indicated these findings were reliable without pleiotropy.CONCLUSION This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk.Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

Improvement of the nutritional support management system for patients in intensive care units

BACKGROUND Nutritional support for patients hospitalized in the intensive care unit(ICU)is an important part of clinical treatment and care,but there are significant implementation difficulties.AIM To introduce a modified nutritional support management system for ICU patients based on closed-loop information management and psychological counseling.METHODS The division of functions,personnel training,system construction,development of an intelligent decision-making software system,quality control,and improvement of the whole process were carried out to systematically manage nutritional support for ICU patients.RESULTS Following the implementation of the whole process management system,the scores of ICU medical staff’s knowledge,attitudes/beliefs,and practices regarding nutritional support were comprehensively enhanced.The proportion of hospital bed-days of total enteral nutrition(EN)in ICU patients increased from 5.58%to 11.46%,and the proportion of EN plus parenteral nutrition increased from 42.71%to 47.07%.The rate of EN initiation within 48 h of ICU admission increased from 37.50%to 48.28%,and the EN compliance rate within 72 h elevated from 20.59%to 31.72%.After the implementation of the project,the Self-rating Anxiety Scale score decreased from 61.07±9.91 points to 52.03±9.02 points,the Self-rating Depression Scale score reduced from 62.47±10.50 points to 56.34±9.83 points,and the ICU stay decreased from 5.76±2.77 d to 5.10±2.12 d.CONCLUSION The nutritional support management system based on closed-loop information management and psychological counseling achieved remarkable results in clinical applications in ICU patients.

Comment on“Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies”

To the Editor:We read with great interest the article by Schulze et al.entitled“Robotic surgery and liver transplantation:A single-center experience of 501 robotic donor hepatectomies”[1].It is the first single-center report including over 500 fully robotic donor hepatectomies.For the donors,the overall complication rate was 6.4%(n=32).Postoperative self-limiting bleeding(0.4%)and bile leakage from the resection plane(1.8%)were rare.

A Novel High-Efficiency Transaction Verification Scheme for Blockchain Systems

Blockchain can realize the reliable storage of a large amount of data that is chronologically related and verifiable within the system.This technology has been widely used and has developed rapidly in big data systems across various fields.An increasing number of users are participating in application systems that use blockchain as their underlying architecture.As the number of transactions and the capital involved in blockchain grow,ensuring information security becomes imperative.Addressing the verification of transactional information security and privacy has emerged as a critical challenge.Blockchain-based verification methods can effectively eliminate the need for centralized third-party organizations.However,the efficiency of nodes in storing and verifying blockchain data faces unprecedented challenges.To address this issue,this paper introduces an efficient verification scheme for transaction security.Initially,it presents a node evaluation module to estimate the activity level of user nodes participating in transactions,accompanied by a probabilistic analysis for all transactions.Subsequently,this paper optimizes the conventional transaction organization form,introduces a heterogeneous Merkle tree storage structure,and designs algorithms for constructing these heterogeneous trees.Theoretical analyses and simulation experiments conclusively demonstrate the superior performance of this scheme.When verifying the same number of transactions,the heterogeneous Merkle tree transmits less data and is more efficient than traditional methods.The findings indicate that the heterogeneous Merkle tree structure is suitable for various blockchain applications,including the Internet of Things.This scheme can markedly enhance the efficiency of information verification and bolster the security of distributed systems.

Game theory attack pricing for mining pools in blockchain-based IoT

The malicious mining pool can sacrifice part of its revenue to employ the computing power of blockchain network.The employed computing power carries out the pool mining attacks on the attacked mining pool.To realize the win-win game between the malicious mining pool and the employee,the paper proposes an Employment Attack Pricing Algorithm(EAPA)of mining pools in blockchain based on game theory.In the EAPA,the paper uses mathematical formulas to express the revenue of malicious mining pools under the employment attack,the revenue increment of malicious mining pools,and the revenue of the employee.It establishes a game model between the malicious mining pool and the employee under the employment attack.Then,the paper proposes an optimal computing power price selection strategy of employment attack based on model derivation.In the strategy,the malicious mining pool analyzes the conditions for the employment attack,and uses the derivative method to find the optimal utilization value of computing power,employees analyze the conditions for accepting employment,and use the derivative method to find the optimal reward value of computing power.Finally,the strategy finds the optimal employment computing power price to realize Nash equilibrium between the malicious mining pool and the employee under the current computing power allocation.The simulation results show that the EAPA could find the employment computing power price that realizes the win-win game between the malicious mining pool and the employee.The EAPA also maximizes the unit computing power revenue of employment and the unit computing power revenue of honest mining in malicious mining pool at the same time.The EAPA outperforms the state-of-the-art methods such as SPSUCP,DPSACP,and FPSUCP.

Coordinated voltage regulation strategy of OLTC and BESS considering switching delay

When large-scale distributed renewable energy power generation systems are connected to the power grid,the risk of grid voltage fluctuations and exceeding the limit increases greatly.Fortunately,the on-load tap changer(OLTC)can adjust the transformer winding tap to maintain the secondary side voltage within the normal range.However,the inevitable delay in switching transformer taps makes it difficult to respond quickly to voltage fluctuations.Moreover,switching the transformer taps frequently will decrease the service life of OLTC.In order to solve this critical issue,a cooperative voltage regulation strategy applied between the battery energy storage systems(BESSs)and OLTSs.is proposed By adjusting the charge and discharge power of BESSs,the OLTC can frequently switch the transformer taps to achieve rapid voltage regulation.The effectiveness of the proposed coordinated regulation strategy is verified in the IEEE 33 node distribution systems.The simulation results show that the proposed coordinated regulation strategy can stabilize the voltage of the distribution network within a normal range and reduce the frequency of tap switching,as such elongating the service life of the equipment.

Middle hepatic vein variation provides a safe path for anterior transection of hepatocellular carcinoma in caudate lobe

To the Editor:Hepatocellular carcinoma(HCC)is one of the main causes of cancer related death worldwide,and new cases are expected to continue to increase in future[1].Surgical resection is still the best way to remove the tumor and improve patient’s prognosis.However,resection of caudate lobe often presents a technical challenge,even to accomplished hepatic surgeons.Caudate lobe is located anterior to the inferior vena cava(IVC)and posterior to the bifurcation of the portal vein(PV),generally consists of three regions:the paracaval portion,the left Spiegel lobe and the process portion[2].The anatomy of the paracaval portion includes the liver parenchyma ventral to the hepatic IVC and the area between the Spiegel lobe and the right lobe adjacent to the middle hepatic vein(MHV)ventrally,which was classified by Couinaud as segment IX[3].Here,we presented a case of HCC with successful downstaging therapy,as well as variation of MHV,which provides a safe path for anterior transection of segment IX.

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver disease.Despite notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of recipients.Unfortunately,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to EAD.Herein,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion stages.Comparison of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))neutrophils.Moreover,we verified this immune niche and its association with EAD occurrence in two independent cohorts.Our findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

Bioactive constituents and action mechanism of Xiaoyao San for treatment of non-alcoholic fatty liver disease

Xiaoyao San(XYS)is a classic Chinese medicine prescription.It is traditionally used to relieve syndrome of“liver stagnation and spleen deficiency”,a common syndrome type in traditional Chinese medicine,through soothing liver,tonifying spleen,and nourishing blood.Correspondingly,XYS has long application in the treatment of depression,dyspepsia and liver diseases.Given the rising of cutting-edge researches on XYS,there’s a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly.

Community analysis of ammonia and nitrite oxidizers in start-up of aerobic granular sludge reactor

A lab-scale sequencing batch reactor （SBR） was set-up and the aerobic granular sludge was successfully incubated using anaerobic granular sludge as seed sludge. Nitrogen was partially removed by simultaneous nitrification and denitrification （SND） via nitrite with free ammonia （FA） of about 10 mg/L. The denaturing gradient gel electrophoresis （DGGE） method was used to investigate community structure of α-Proteobacteria, β-Proteobacteria, ammonia oxidizing bacteria （AOB）, and Nitrospira populations during start-up. The population sizes of bacteria, AOB and Nitrospira were examined using real-time PCR method. The analysis of community structure and Shannon index showed that stable structure of AOB population was obtained at day 35, while the communities of α- Proteobacteria, β-Proteobacteria, and Nitrospira became stable after day 45. At stable stage, the average cell densities were 1.1× 10^12, 2.2×10^10 and 1.0×10^10 cells/L for bacteria, AOB and Nitrospira, respectively. The relationship between characteristics of nitrifying bacteria community and nitrogenous substrate utilization constant was discussed by calculating Pearson correlation. Certain correlation seemed to exist between population size, biodiversity, and degradation constant. And the influence of population size might be greater than that of biodiversity.

Ionic liquid based dispersive liquid-liquid microextraction of aromatic amines in water samples

In this work, a new microextraction method termed ionic liquid based dispersive liquid-liquid microextraction （IL-DLLME） was demonstrated for the extraction of 2-methylaniline, 4-chloroaniline, 1-naphthylamine and 4-aminobiphenyl in aqueous matrices. After extraction the ionic liquid （IL） phase was injected directly into the high performance liquid chromatography （HPLC） system for determination. Some parameters that might affect the extraction efficiency were optimized. Under the optimum conditions, good linear relationship, sensitivity and reproducibility were obtained. The limits of detection （LOD, S/N = 3） for the four analytes were in the range of 0.45-2.6 μg L^-1. The relative standard deviations （R.S.D., n = 6） were in the range of 6.2-9.8%. This method was applied for the analysis of the real water samples. The recoveries ranged from 93.4 to 106.4%. The main advantages of the method are high speed, high recovery, good repeatability and volatile organic solvent-free.

A new approach for time effect analysis of settlement for single pile based on virtual soil-pile model

A new approach is proposed to analyze the settlement behavior for single pile embedded in layered soils. Firstly, soil layers surrounding pile shaft are simulated by using distributed Voigt model, and finite soil layers under the pile end are assumed to be virtual soil-pile whose cross-section area is the same as that of the pile shaft. Then, by means of Laplace transform and impedance function transfer method to solve the static equilibrium equation of pile, the analytical solution of the displacement impedance fimction at the pile head is derived. Furthermore, the analytical solution of the settlement at the head of single pile is theoretically derived by virtue of convolution theorem. Based on these solutions, the influences of parameters of soil-pile system on the settlement behavior for single pile are analyzed. Also, comparison of the load-settlement response for two well-instrumented field tests in multilayered soils is given to demonstrate the effectiveness and accuracy of the proposed approach. It can be noted that the presented solution can be used to calculate the settlement of single pile for the preliminary design of pile foundation.

Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A(H7N9) Infection: A Hint for COVID-19 Treatment

2013年,H7N9病毒在哺乳动物宿主之间迅速传播,并具有人与人之间传播的风险。患者表现为重症肺炎、急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)和呼吸衰竭。间充质干细胞(mesenchymal stem cell,MSC)移植在病毒性肺炎的治疗中有广阔的前景,并于2013年作为应急性治疗方法来治疗H7N9感染的ARDS。该研究在单中心开展,为开放式临床研究。根据自愿和知情同意的原则,17例H7N9感染的ARDS患者移植同种异体经血来源的MSC作为治疗组,44例H7N9感染的ARDS患者作为对照组。与对照组相比,MSC移植显著降低了ARDS病死率(MSC治疗组和对照组死亡率分别为17.6%和54.5%)。此外,在对4名MSC移植患者进行为期5年的随访中,未发现MSC移植产生有害影响。总体而言,该研究结果表明MSC移植显著提高了H7N9感染的ARDS的存活率,并为开展临床前和临床应用MSC治疗H7N9感染的ARDS的研究提供了理论基础。由于H7N9和新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)临床表现相似(如ARDS和呼吸衰竭),并继发多器官功能障碍,因此基于MSC的疗法可能为COVID-19所致的ARDS患者获益。