Procyanidin B2 protects against diet-induced obesity and non-alcoholic fatty liver disease via the modulation of the gut microbiota in rabbits

BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity,but the mechanisms underlying these effects are unclear.AIM To investigate the effects of procyanidin B2(PB2)on non-alcoholic fatty liver disease and to explore the possible mechanism.METHODS Thirty male New Zealand white rabbits were randomized into three groups.All of them were fed either a high-fat-cholesterol diet(HCD)or chow diet.HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk.Body weight and food intake were evaluated once a week.Serum biomarkers,such as total cholesterols,triglycerides,and aspartate transaminase,were detected.All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections.Moreover,several lipogenic genes and gut microbiota(by 16S rRNA sequencing)were investigated to explore the possible mechanism.RESULTS The HCD group had higher body weight,liver index,serum lipid profile,insulin resistance,serum glucose,and hepatic steatosis compared to the CHOW group.PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver.PB2 also ameliorated low-grade inflammation,which was reflected by serum lipopolysaccharides and improved insulin resistance.In rabbit liver,PB2 prevented the upregulation of steroid response element binding protein 1c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase,compared to the HCD group.Moreover,HCD led to a decrease of Bacteroidetes in gut microbiota.PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.

Ventilatory effect of normal frequency jet ventilation in non-intubated anesthesia in the treatment of the palmar hyperhidrosis

Objective: To evaluate the ventilatory effect of normal frequency jet ventilation via Wei jet nasal airway in non-intubated anesthesia in the treatment of the palmar hyperhidrosis (PH). Methods: 62 patients with PH undergoing video-assisted thoracoscopic sympathectomy, aged 18~35 years, ASA I-II, were randomized into two groups: intubated group (group T) and normal-frequency jet ventilation group (group J). After induction tracheal tubes were inserted in Group T and Wei nasal airway were inserted in group J. The heart rate(HR),saturation pulse oxygen (SPO2), mean artery pressure (MAP) and end-tidal carbon dioxide partial pressure (PETCO2) were recorded at following time points: before induction (T0),1 min after induction (T1), 1 min after tube insertion/ intubation (T2), when trocars were inserted and carbon dioxide was inflated (T3), during lung recruitment maneuver and the chest closure (T4), the moment of extubation (T5), 15 min after extubation (T6). Blood samples were taken from left radial artery for blood gas analysis to monitor carbon dioxide partial pressure, arterial oxygen partial pressure, PH ,the BE at T0, T4, T6.The duration of anesthesia, awaking time ,the dosage of the propofol and the remifentanil, the intraoperative and postoperative adverse events were recorded. Results: Compared with group T, the HR and MAP were more stable in group J. The awaking time in the group J were significantly shorter than those in group T (P<0.05), the dosage of the remifentanil in group J was significantly less than that in group T (P<0.05), The incidences of throat discomfort, nausea and vomiting were lower than those in group T (P<0.05). Conclusion: Normal-frequency jet ventilation via Wei jet nasal airway in non-intubated anesthesia in the treatment of the (PH)is feasible, which can reduce stress response and make hemodynamics stable without the complications of tracheal intubation.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

Control and Stability of Large-scale Power System with Highly Distributed Renewable Energy Generation:Viewpoints from Six Aspects

Power systems are moving toward a low-carbon or carbon-neutral future where high penetration of renewables is expected.With conventional fossil-fueled synchronous generators in the transmission network being replaced by renewable energy generation which is highly distributed across the entire grid,new challenges are emerging to the control and stability of large-scale power systems.New analysis and control methods are needed for power systems to cope with the ongoing transformation.In the CSEE JPES forum,six leading experts were invited to deliver keynote speeches,and the participating researchers and professionals had extensive exchanges and discussions on the control and stability of power systems.Specifically,potential changes and challenges of power systems with high penetration of renewable energy generation were introduced and explained,and advanced control methods were proposed and analyzed for the transient stability enhancement of power grids.

Transient Stability Analysis of Large-scale Power Systems:A Survey

Transient stability analysis is a key problem in power system operation and planning.This paper aims at giving a comprehensive review on the modeling ideas and analysis methods for transient stability of large-scale power systems.For model construction,the general modeling of traditional power systems and special modeling for renewable generations and high-voltage direct-current transmissions are introduced.For transient stability analysis,Lyapunov based methods and non-Lyapunov based methods are thoroughly reviewed.In Lya-punov based methods,we focus on the energy function method,the sum-of-squares based method and decentralized stability analysis methods.Meanwhile,in non-Lyapunov based methods,the time-domain simulation,extended equal-area criterion and data-driven based methods are considered.The basic working principles,features and recent research progresses of all the above-mentioned methods are described in detail.In particular,their performances on several aspects,such as computational speed,conservativeness of stability region estimation or stability margin calculation,and adaptability to various types of system models,are mentioned.Finally,a brief discussion of potential directions for future research on transient stability analysis of large-scale power systems is included.Index Terms-connective stability,large-scale system analysis,Lyapunov functions,power systems,transient stability analysis.

Probabilistic Optimal Power Flow Considering the Dependence of Multiple Wind Farms Using Pair Diffusive Kernel Copula

As wind farms are commonly installed in areas with abundant wind resources,spatial dependence of wind speed among nearby wind farms should be considered when modeling a power system with large-scale wind power.In this paper,a novel bivariate non-parametric copula,and a bivariate diffusive kernel(BDK)copula are proposed to formulate the dependence between random variables.BDK copula is then applied to higher dimension using the pair-copula method and is named as pair diffusive kernel(PDK)copula,offering flexibility to formulate the complicated dependent structure of multiple random variables.Also,a quasi-Monte Carlo method is elaborated in the sampling procedure based on the combination of the Sobol sequence and the Rosen-blatt transformation of the PDK copula,to generate correlated wind speed samples.The proposed method is applied to solve probabilistic optimal power flow(POPF)problems.The effectiveness of the BDK copula is validated in copula definitions.Then,three different data sets are used in various goodness-of-fit tests to verify the superior performance of the PDK copula,which facilitates in formulating the dependence structure of wind speeds at different wind farms.Furthermore,samples obtained from the PDK copula are used to solve POPF problems,which are modeled on three modified IEEE 57-bus power systems.Compared to the Gaussian,T,and parametric-pair copulas,the results obtained from the PDK copula are superior in formulating the complicated dependence,thus solving POPF problems.

Multi-parametric Sensitivity Analysis of Improved Transformer Thermal Models Considering Nonlinear Effect of Oil Time Constant

This paper aims to develop an approach to investigating the effect of a particular parameter on the output accuracy of transformer thermal models,i.e.sensitivity analysis,which can not only reveal the most sensitive parameter of a thermal model but also improve model output accuracies.For the first time,the nonlinear time constant(NTC)of transformer oil is proposed to reshape three practical top-oil temperature models based on an expression of nonlinear thermal conductance:the modified IEEE clause 7 model,Swift’s model,and Susa’s model.Then,the multi-parametric sensitivity analysis(MPSA)is undertaken to reveal the effect of each parameter on the model output accuracy.Through onsite data validation,the results show that the accuracy performance of the proposed NTC thermal models are improved significantly by considering the nonlinear effect of oil time constant.Moreover,the derived sensitivity performances can clearly reveal the most dominant parameter of the model,so as to simplify the model parameter identification process by reducing the number of insensitive parameters.Finally,the heat-run test data is used as a reference to validate parameters optimized through a genetic algorithm(GA),which demonstrates that the proposed NTC IEEE model has not only one sensitive parameter but also superior accuracy performance.

Stability Analysis of DC-DC Converters with Energy Balance Control

With variation of parameters,DC-DC converters may change from a stable state to an unstable state,which severely degrades the performances of the converter system.In this article,by establishing the state-space average model,the stability and bifurcation of a boost and a buck-boost converter with energy balance control(EBC)is studied,respectively.Then the stability boundary and stable parameter domains are accurately predicted.The obtained stability region provides a parameter regulating range for converter design.Furthermore,compared with the one-cycle control(OCC)method,the EBC possesses an extended stable parameter domain,while avoiding unstable behaviors such as Hopf bifurcation,Quasi-periodic Oscillation even chaos,etc.The theoretic analysis is well validated through simulation and experiment.

Many-objective Optimization Method Based on Dimension Reduction for Operation of Large-scale Cooling Energy Systems

Large-scale cooling energy system has developed well in the past decade.However,its optimization is still a problem to be tackled due to the nonlinearity and large scale of existing systems.Reducing the scale of problems without oversimplifying the actual system model is a big challenge nowadays.This paper proposes a dimension reduction-based many-objective optimization(DRMO)method to solve an accurate nonlinear model of a practical large-scale cooling energy system.In the first stage,many-objective and many-variable of the large system are pre-processed to reduce the overall scale of the optimization problem.The relationships between many objectives are analyzed to find a few representative objectives.Key control variables are extracted to reduce the dimension of variables and the number of equality constraints.In the second stage,the manyobjective group search optimization(GSO)method is used to solve the low-dimensional nonlinear model,and a Pareto-front is obtained.In the final stage,candidate solutions along the Paretofront are graded on many-objective levels of system operators.The candidate solution with the highest average utility value is selected as the best running mode.Simulations are carried out on a 619-node-614-branch cooling system,and results show the ability of the proposed method in solving large-scale system operation problems.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study

Background: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. Methods: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. Results: During 6-month follow-up, 87 participants occurred bleeding events. For every 1×10^9/L increase in leukocyte count, the risk of bleeding increased by 11%(hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99–1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75×10^9/L. For leukocyte counts < 6.75×10^9/L, the HR (95% CI) was 0.88 (0.69–1.13), and for leukocyte counts ≥ 6.75×10^9/L, the HR (95% CI) was 1.28 (1.09–1.51). Conclusion: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran.

A mutation of Aspergillus niger for hyper-production of citric acid from corn meal hydrolysate in a bioreactor

The properties of the screened mutants for hyper-production of citric acid induced by carbon （12C6＋） ion beams and X-ray irradiation were investigated in our current study. Among these mutants, mutant H4002 screened from 12C6＋ ion irradiation had a higher yield of citric acid production than the parental strain in a 250-ml shaking flash. These expanded submerged experiments in a bioreactor were also carried out for mutant H4002. The results showed that （177.7-196.0） g/L citric acid was accumulated by H4002 through exploiting corn meal hydrolysate （containing initial 200.0-235.7 g/L sugar） with the productivity of （2.96-3.27） g/（L.h）. This was especially true when the initial sugar concentration was 210 g/L, and the best economical citric acid production reached （187.5±0.7） g/L with a productivity of 3.13 g/（L.h）. It was observed that mutant H4002 can utilize low-cost corn meal as a feedstock to efficiently produce citric acid. These results imply that the H4002 strain has the industrial production potentiality for citric acid and offers strong competition for the citric acid industry.

Treatment of chronic heart failure in the 21st century: A new era of biomedical engineering has come

Chronic heart failure (CHF) is a challenging burden on public health. Therapeutic strategies for CHF have developed rapidly in the past decades from conventional medical therapy, which mainly includes administration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists, to biomedical engineering methods, which include interventional engineering, such as percutaneous balloon mitral valvotomy, percutaneous coronary intervention, catheter ablation, biventricular pacing or cardiac resynchronization therapy (CRT) and CRT-defibrillator use, and implantable cardioverter defibrillator use;mechanical engineering, such as left ventricular assistant device use, internal artery balloon counteq^ulsation, cardiac support device use, and total artificial heart implantation;surgical engineering, such as coronary artery bypass graft, valve replacement or repair of rheumatic or congenital heart diseases, and heart transplantation (HT);regenerate engineering, which includes gene therapy, stem cell transplantation, and tissue engineering;and rehabilitating engineering, which includes exercise training, low-salt diet, nursing, psychological interventions, health education, and external counterpulsation/enhanced external counterpulsation in the outpatient department. These biomedical engineering therapies have greatly improved the symptoms of CHF and life expectancy. To date, pharmacotherapy, which is based on evidence-based medicine, large-scale, multi-center, randomized controlled clinical trials, is still a major treatment option for CHF;the current interventional and mechanical device engineering treatment for advanced CHF is not enough owing to its individual status. In place of HT or the use of a total artificial heart, stem cell technology and gene therapy in regenerate engineering for CHF are very promising. However, each therapy has its advantages and disadvantages, and it is currently possible to select better therapeutic strategies for patients with CHF according to cost-efficacy analyses of these therapies. Taken together, we think that a new era of biomedical engineering for CHF has begun.

Novel strategies halt cardiovascular, diabetes, and cancer strips

In this article, we introduce briefly several strategies for preventing atherosclerotic cardiovascular disease and promoting healthcare for non-communicable diseases (NCDs). These novel strategies include four core elements of health-sleep, emotion, exercise, and diet-and consist of SEED intervention (SEEDi) and E(e)SEEDi due to supplementation of the environment as a core element, and Hu's healthy lifestyles intervention (HHLi) which originates from E(e)SEED-BasED healthy lifestyles. They are suitable for the early evaluation of risk factors, and play a key role in the prevention and management of human NCDs when combined with the RT-ABCDEF strategy and the Grade 210 prevention, which include obesity-OSA-hypertension syndrome and C-type hypertension, especially in halting cardiovascular, diabetes and cancer (CDC) strips we first discovered. After successful clinical practice, we may expect our novel strategies for controlling these chronic diseases according to the conception of mass prevention and treatment.

Generation maintenance scheduling based on multiple objectives and their relationship analysis

In a market environment of power systems, each producer pursues its maximal profit while the independent system operator is in charge of the system reliability and the minimization of the total generation cost when generating the generation maintenance scheduling(GMS). Thus, the GMS is inherently a multi-objective optimization problem as its objectives usually conflict with each other. This paper proposes a multi-objective GMS model in a market environment which includes three types of objectives, i.e., each producer's profit, the system reliability, and the total generation cost. The GMS model has been solved by the group search optimizer with multiple producers(GSOMP) on two test systems. The simulation results show that the model is well solved by the GSOMP with a set of evenly distributed Pareto-optimal solutions obtained. The simulation results also illustrate that one producer's profit conflicts with another one's, that the total generation cost does not conflict with the profit of the producer possessing the cheapest units while the total generation cost conflicts with the other producers' profits, and that the reliability objective conflicts with the other objectives.

Development and validation of a deep learning model to screen hypokalemia from electrocardiogram in emergency patients

Background:A deep learning model(DLM)that enables non-invasive hypokalemia screening from an electrocardiogram(ECG)may improve the detection of this life-threatening condition.This study aimed to develop and evaluate the performance of a DLM for the detection of hypokalemia from the ECGs of emergency patients.Methods:We used a total of 9908 ECG data from emergency patients who were admitted at the Second Affiliated Hospital of Nanchang University,Jiangxi,China,from September 2017 to October 2020.The DLM was trained using 12 ECG leads(lead Ⅰ,Ⅱ,Ⅲ,aVR,aVL,aVF,and V1–6)to detect patients with serum potassium concentrations<3.5 mmol/L and was validated using retrospective data from the Jiangling branch of the Second Affiliated Hospital of Nanchang University.The blood draw was completed within 10 min before and after the ECG examination,and there was no new or ongoing infusion during this period.Results:We used 6904 ECGs and 1726 ECGs as development and internal validation data sets,respectively.In addition,1278 ECGs from the Jiangling branch of the Second Affiliated Hospital of Nanchang University were used as external validation data sets.Using 12 ECG leads(leads Ⅰ,Ⅱ,Ⅲ,aVR,aVL,aVF,and V1–6),the area under the receiver operating characteristic curve(AUC)of the DLM was 0.80(95%confidence interval[CI]:0.77–0.82)for the internal validation data set.Using an optimal operating point yielded a sensitivity of 71.4%and a specificity of 77.1%.Using the same 12 ECG leads,the external validation data set resulted in an AUC for the DLM of 0.77(95%CI:0.75–0.79).Using an optimal operating point yielded a sensitivity of 70.0%and a specificity of 69.1%.Conclusions:In this study,using 12 ECG leads,a DLM detected hypokalemia in emergency patients with an AUC of 0.77 to 0.80.Artificial intelligence could be used to analyze an ECG to quickly screen for hypokalemia.

Investigation of Mechanism of Premature Ovarian Failure Regulation by Kidney-tonifying Herbs and Liver-clearing Herbs in Dingjing Decoction

Objective To investigate the mechanisms through which kidney-tonifying herbs（KTHs） and liver-clearing herbs（LCHs） in Dingjing Decoction（DJD） regulate premature ovarian failure（POF）. Methods One hundred and fifty Sprague-Dawley rats were randomly divided into five groups such as control, model, KTHs, LCHs, and DJD groups. POF-related biological molecules were examined. Factor analysis was performed to investigate the regulatory networks and key biomolecules involved in mediating POF after treatment with KTHs and LCHs. Results The master regulatory factors in the reproductive endocrine network associated with KTHs intervention included four molecules in the pituitary-ovarian axis, cortisol（CORT） in the target gland of pituitary-adrenal axis, and some molecules in the hypothalamus. In contrast, the master regulatory factors associated with LCHs intervention included four molecules in the pituitary-ovarian axis and some molecules in the hypothalamus; No biomolecules in the pituitary-adrenal axis were involved in the LCH-mediated mechanisms.Gonadotropin-releasing hormone（Gn RH）, which was identified as a common biological molecule in the hypothalamus, was involved in regulating the reproductive endocrine network in association with KTHs intervention. Conclusion KTHs directly regulates biological molecules in the pituitary-adrenal axis and indirectly regulates those in the pituitary-adrenal axis through the hypothalamus, while the LCHs only exert its effects indirectly. Gn RH is the key biological molecule associated with KTHs intervention.