Research progress on the mechanism of traditional Chinese medicine in the treatment of autoimmune hepatitis

Autoimmune hepatitis is an inflammatory liver disease primarily mediated by T cell.It has not been fully elucidated about the pathogenesis,and it is presently thought to be related to genetic susceptibility,infection and environmental triggers,and abnormal autoimmune regulation.Recent studies have found that traditional Chinese medicine can improve the biochemical indicators and clinical symptoms of patients with autoimmune hepatitis.This article reviews the specific mechanism of traditional Chinese medicine on treating autoimmune hepatitis in order to propose new ideas for its clinical diagnosis and treatment.

Advances in toxicological studies of Radix Phytolaccae

Radix Phytolaccae is the dried root of Phytolacca acinosa Roxb or P.ameri-cana L,which is commonly used as a traditional Chinese medicine to treat diseases like cirrhotic ascites,hepatitis B,nephrotic syndrome,psoriasis,etc.However,there is no exact basis for its clinical application safety.In this paper,the toxic effects and mechanism of Saponin A(EsA),the main component of Radix Phytolaccae,were summarized by searching the results and reports of toxicology related to the plant from 1991 to 2023 on CNKI and pubmed,aiming to provide reference for the toxicological research and future research direction of Radix Phytolaccae,so that Radix Phytolaccae can be safely and effectively used in clinical practice.

Proper beverages may reduce the risk of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, characterized by a progressive decline in cognitive ability. Around 50 million people worldwide are reportedly affected, with annual losses estimated at about $1 trillion [1]. Nevertheless, there remains unknown about the exact pathological mechanisms of AD and currently available treatments have a lack of efficacy. Thus, experts have reached a consensus that interventions in the preclinical stage of AD should be prioritized [2], especially when the amount of patients is set to reach 78 million by the end of this decade [3]. Recently, the proposition “integrating food and nutrition into healthcare” has been promoted [4]. Prevention from dietary eating and drinking may be an effective and age-friendly method. Nowadays, many beverages have been proven to offer great preventative benefits to AD like coffee, soy milk, tea, and wine. Coffee, consumed by tens of thousands of people every day, has been proven in several epidemiological studies to have a protective effect against AD [5-7]. A study including 411 individuals shows that significant negative correlation between stratified lifetime coffee intake and β-amyloid positivity [8]. In other words, higher coffee intake (≥ 2 cups/day) is associated with lower risk of AD. However, a Mendelian randomization (MR) analysis came to the opposite conclusion, with an additional 1 cup of coffee per day being associated with a 1.16-fold increased risk of developing AD [9]. In meta-analyses of cohort studies, it was proposed that there was a non-linear “U-shaped” link between coffee consumption and AD, with 3-4 cups per day being optimal [10]. In addition to the possibility that different conclusions are due to inconsistent estimations of coffee intake and populations in these studies, research recently proposed a hypothesis that the cytochrome P450 1A2 played an essential role in the metabolism of coffee in the human body [11]. Rs762551 is its most representative and commonly studied single nucleotide polymorphism. In detail, carriers of the rs762551 gene metabolize caffeine more rapidly and are at greater risk of developing AD when they consume large amounts of coffee. Conversely, people with slow caffeine metabolism who consume more coffee would have a preventive effect on AD, which might be a result of being exposed to coffee for a longer duration of time to the point of absorbing more potential beneficial effects of caffeine.

血清铁蛋白对急性冠脉综合征介入术后造影剂引起肾病发生的预测研究

目的探讨血清铁蛋白(SF)对急性冠脉综合征(ACS)患者经皮冠脉介入术(PCI)后造影剂引起肾病(CIN)发生的影响。方法选取2015年1月—2017年6月承德市中心医院心内科行PCI治疗的ACS患者368例。据入院发病时血清铁蛋白水平以三分位数法分为3组(A组SF<160 ng/ml,B组SF 160 ng/ml～<258 ng/ml,C组SF≥258 ng/ml),比较不同组ACS患者PCI术后CIN发生率,分析其影响因素。结果 368例患者发生CIN 39例,发生率为10.6%;A组106例,发生CIN 9例,发生率为8.5%;B组153例,发生CIN 11例,发生率为7.2%;C组109例,发生CIN 19例,发生率为17.4%;3组间比较差异有统计学意义(P <0.05)。ROC曲线显示SF为239.5 ng/ml时预测CIN发生具有68.4%的敏感性和65.2%的特异性(曲线下面积为0.727,95%CI:0.663,0.790);多因素Logistic回归分析显示术前SF≥258 ng/ml,[O^R=2.677(95%CI:1.606,4.462),P=0.000]、血清肌酐升高[O^R=1.029(95%CI:1.001,1.058),P=0.046]、血清尿素升高[O^R=1.553(95%CI:1.145,2.107),P=0.005]是CIN发生的危险因素,射血分数升高[O^R=-0.054(95%CI:0.898,0.999),P=0.048]是CIN发生的保护因素。结论高水平SF、术前肾功能异常对ACS患者介入治疗后CIN具有预测作用,射血分数是CIN发生的保护因素。

Research progress of traditional Chinese medicine compound in the treatment of gout based on intestinal flora

Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long history and remarkable clinical effect in treating gout patients,and has been widely used.Intestinal flora and its metabolites are the focus of current research,which can promote intestinal mucosal barrier,improve immunity and improve metabolism.The regulation of intestinal flora can reduce serum uric acid and inhibit inflammation to fight gouty arthritis.Moreover,the mechanism of intestinal flora is related to the spleen in Chinese medicine theory.Therefore,this study discusses the research mechanism and clinical application of traditional Chinese medicine compound in treating gout by regulating intestinal flora,and provides theoretical basis for the clinical application of traditional Chinese medicine and the expansion of new dosage forms.

Efficacy and safety of mild-warm moxibustion in treating diarrhea-predominant irritable bowel syndrome(spleen deficiency and dampness excess syndrome):a study protocol for a randomized controlled trial

1Background:Irritable bowel syndrome(IBS)is a disorder of bowel function,and diarrhea-predominant irritable bowel syndrome(IBS-D)is the most common.The current treatment for IBS-D is focused on improving patients’gastrointestinal-related symptoms,but there are limitations such as unstable effects and adverse drug reactions.Acupuncture and moxibustion exerts advantages in treating IBS-D.They include several forms,of which moxibustion is one of the most commonly used.And moxibustion is a common way used in treating IBS-D,but there is a lack of relevant evidence-based medical research data.This protocol aims to compare the efficacy of moxibustion(mild-warm moxibustion)in treating IBS-D(spleen deficiency and dampness excess syndrome)with the first-line treatment.Methods:In this prospective,parallel,randomized controlled trial(RCT)protocol,patients will be randomly allocated for 4-week treatment or control therapies and then 4-week follow-up in both groups.We will use Irritable Bowel Syndrome-Symptom Severity Scale(IBS-SSS)score,Irritable Bowel Syndrome-Quality of Life(IBS-QOL)score,serum brain-gut peptide levels,and traditional Chinese medicine(TCM)syndrome scale score to produce more evidence on IBS-D treatment with moxibustion.Finally,we will use SPSS 22.0 software to statistically analyze the data.Discussion:Mild-warm moxibustion is a complementary alternative therapy that fits with the pathogenesis of IBS-D.We hope to see more clinical evidence for mild-warm moxibustion against IBS-D that this RCT supported.

Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats

Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles. However, no satisfactory treatment is currently available. Hypoxia-inducible factor 1α is a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis. In this study, a rat model of brachial plexus avulsion-reimplantation was established, in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted. Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion. Rats were randomly divided into five groups: phosphate-buffered saline, negative control of lentivirus, hypoxia-inducible factor 1α(hypoxia-inducible factor 1α overexpression lentivirus), gel(pluronic F-127 hydrogel), and gel + hypoxia-inducible factor 1α(pluronic F-127 hydrogel + hypoxia-inducible factor 1α overexpression lentivirus). The Terzis grooming test was performed to assess recovery of motor function. Scores were higher in the hypoxia-inducible factor 1α and gel +hypoxia-inducible factor 1α groups(in particular the gel + hypoxia-inducible factor 1α group) compared with the phosphate-buffered saline group. Electrophysiology, fluorogold retrograde tracing, and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons, motor endplates, and angiogenesis. Compared with the phosphate-buffered saline group, action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor1α groups. Meanwhile, the number of fluorogold-positive cells and ChAT-positive neurons, neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments), and the number of motor endplates in biceps brachii(identified by α-bungarotoxin) were all visibly increased, as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1α and gel + hypoxia-inducible factor 1α groups. Taken together, delivery of hypoxia-inducible factor 1α overexpression lentiviral vectors mediated by pluronic F-127 effectively promotes spinal root regeneration and functional recovery post-brachial plexus avulsion. All animal procedures were approved by the Institutional Animal Care and Use Committee of Guangdong Medical University, China.

Air combat decision-making of multiple UCAVs based on constraint strategy games

Game theory can be applied to the air combat decision-making problem of multiple unmanned combat air vehicles(UCAVs).However,it is difficult to have satisfactory decision-making results completely relying on air combat situation information,because there is a lot of time-sensitive information in a complex air combat environment.In this paper,a constraint strategy game approach is developed to generate intelligent decision-making for multiple UCAVs in complex air combat environment with air combat situation information and time-sensitive information.Initially,a constraint strategy game is employed to model attack-defense decision-making problem in complex air combat environment.Then,an algorithm is proposed for solving the constraint strategy game based on linear programming and linear inequality(CSG-LL).Finally,an example is given to illustrate the effectiveness of the proposed approach.

18β-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload

Summary:Ranolazine,a late sodium current inhibitor,has been demonstrated to be effective on heart failure.18B-glycyrrhetinic acid(18β-GA)has the similar inhibitory effect on late sodium currents.However,its effect on diastolic function is still unknown.This study aimed to determine whether 18β-GA can improve the diastolic function and to explore the underlying mechanisms.Eighty male Sprague Dawley(SD)rats of Langendorff model were randomly divided into the following groups:group A,normal cardiac perfusion group;group B,ischemia-reperfusion group;group C,ischemia-reperfusion with anemoniasulcata toxinⅡ(ATX-Ⅱ);group D,ranolazine group;and group E,18β-GA group with four different concentrations.Furthermore,a pressure-overloaded rat model induced by trans-aortic constriction(TAC)was established.Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC.Changes of free intracellular calcium(Ca27)concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents.With the intervention of ATX-Ⅱon ischemia reperfusion injury group,5 umol/L ranolazine,and 5,10,20,40μmol/L 18β-GA could improve ATX-I-induced cardiac diastolic dysfunction.630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats.18B-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes.The study demonstrates that 18B-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats.The mechanism may be attributed to the inhibition of enhanced late sodium currents.

Fatal community-acquired bloodstream infection caused by Klebsiella variicola:A case report

BACKGROUND Klebsiella pneumoniae(K.pneumoniae)is an infective microorganism of worldwide concern because of its varied manifestations and life-threatening potential.Genetic analyses have revealed that subspecies of K.pneumoniae exhibit higher virulence and mortality.However,infections with Klebsiella subspecies are often misdiagnosed and underestimated in the clinic because of difficulties in distinguishing K.pneumoniae from its subspecies using routine tests.This case study reports the rapid and fatal effects of K.pneumoniae subspecies.CASE SUMMARY A 52-year-old male patient was febrile and admitted to hospital.Examinations excluded viral and fungal causes along with mycoplasma/chlamydia and parasitic infections.Bacterial cultures revealed blood-borne K.pneumoniae sensitive to carbapenem antibiotics,although corresponding treatment failed to improve the patient’s symptoms.His condition worsened and death occurred within 72 h of symptom onset from sepsis shock.Application of the PMseq-DNA Pro high throughput gene detection assay was implemented with results obtained after death showing a mixed infection of K.pneumoniae and Klebsiella variicola(K.variicola).Clinical evidence suggested that K.variicola rather than K.pneumoniae contributed to the patient’s poor prognosis.CONCLUSION This is the first case report to show patient death from Klebsiella subspecies infection within a short period of time.This case provides a timely reminder of the clinical hazards posed by Klebsiella subspecies and highlights the limitations of classical laboratory methods in guiding anti-infective therapies for complex cases.Moreover,this report serves as reference for physicians diagnosing similar diseases and provides a recommendation to employ early genetic detection to aid patient diagnosis and management.

Global Functional Network Connectivity Disturbances in Parkinson’s Disease with Mild Cognitive Impairment by Resting-State Functional MRI

Examining the spontaneous BOLD activity to understand the neural mechanism of Parkinson’s disease(PD)with mild cognitive impairment(MCI)is a focus in resting-state functional MRI(rs-fMRI)studies.This study aimed to investigate the alteration of brain functional connectivity in PD with MCI in a systematical way at two levels:functional connectivity analysis within resting state networks(RSNs)and functional network connectivity(FNC)analysis.Using group independent component analysis(ICA)on rs-fMRI data acquired from 30 participants(14 healthy controls and 16 PD patients with MCI),16 RSNs were identified,and functional connectivity analysis within the RSNs and FNC analysis were carried out between groups.Compared to controls,patients with PD showed decreased functional connectivity within putamen network,thalamus network,cerebellar network,attention network,and self-referential network,and increased functional connectivity within execution network.Globally disturbed,mostly increased functional connectivity of FNC was observed in PD group,and insular network and execution network were the dominant network with extensively increased functional connectivity with other RSNs.Cerebellar network showed decreased functional connectivity with caudate network,insular network,and self-referential network.In general,decreased functional connectivity within RSNs and globally disturbed,mostly increased functional connectivity of FNC may be characteristics of PD.Increased functional connectivity within execution network may be an early marker of PD.The multi-perspective study based on RSNs may be a valuable means to assess functional changes corresponding to specific RSN,contributing to the understanding of the neural mechanism of PD.

Molecular mechanism of Herba Eupatorii in treating COVID-19 based on network pharmacology and molecular docking

Objective:To explore the therapeutic target and molecular mechanism of Herba Eupatorii in the intervention of COVID-19(coronavirus disease 2019)by network pharmacology.Methods:TCMSP(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)and TCMIP V2.0(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine)databases were used to search the active ingredients and corresponding drug targets of Herba Eupatorii.Related targets of COVID-19 were searched in Genecards,pharmGKB,CTD,Drugbank and TTD databases.After the intersection targets were selected using VENNY 2.1 online platform,the PPI(protein-protein interaction)network was downloaded into STRING database,and the data were analyzed and sorted out using Cytoscape software to obtain the potential key targets for the treatment of COVID-19 by Herba Eupatorii.At the same time,using the data of active ingredients and intersection targets,a network of"TCM-active ingredients-key targets"was constructed in Cytoscape software to screen out chemical molecules with potential therapeutic effects.GO(Gene Ontology)functional enrichment analysis and KEGG(Kyoto Encyclopedia of Genes)pathway enrichment analysis of key target proteins were performed by R software.AutoDock Vina program was used for molecular docking of the top 5 active ingredients and key targets to calculate the minimum binding energy.Results:There were 26 active ingredients,160 targets,and 1969 pathogenic genes of COVID-19,among which 59 genes were intersection targets of drugs and diseases.After PPI network screening,the key target proteins were AKT1(RAC-alpha serine/threonine-protein kinase),JUN(transcription factor AP-1),TP53(cellular tumor antigen p53),ACTB(actin beta)and EGFR(epidermal growth factor receptor).Through the network of"TCM-Active Ingredients-Key Targets",Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate were identified as the active ingredients with potential therapeutic effects in the treatment of COVID-19.After R software was used for GO enrichment analysis,1978 GO items were obtained(P<0.05),including 1870 BP items,26 CC items and 82 MF items.149 pathways were obtained by KEGG enrichment analysis(P<0.05).It mainly involves IL-17(interleukin-17)signaling pathway,TNF(tumor necrosis factor)signaling pathway,C-type lectin receptor signaling pathway,PI3K-Akt(phosphatidylinositol 3 kinase-protein kinase B)signaling pathway,and T Cell receptor signaling pathway,etc.The molecular docking results showed that the active ingredients had good binding activity with key targets.Conclusion:Through the potential chemical constituents of Luteolin,Eupatolin,Stigmasterol,Eupatoriopicrin and Dammaradienyl acetate,Herba Eupatorii may act on AKT1,JUN,TP53,ACTB,EGFR and other targets.Involvement in IL-17 signaling pathway,TNF signaling pathway,C-Type Lectin receptor signaling pathway,PI3K-Akt signaling pathway,T Cell receptor signaling pathway and other pathways play an anti-inflammatory and antiviral roles in intervening in the occurrence and development of COVID-19.

高综合性能无色透明聚酰亚胺薄膜的制备

以2,2’-双(三氟甲氧基)联苯-4,4’-二胺(TFMOB)/2,2’-双(三氟甲基)联苯-4,4’-二胺(TFMB)为二胺单体,分别与六氟异丙基邻苯二甲酸酐(6FDA)和4,4’-(4,4’-异丙基二苯氧基)双(邻苯二甲酸酐)(BPADA)2种二酐单体聚合,制备了含三氟甲氧基(―OCF_(3))的新型无色透明聚酰亚胺(CPI)薄膜.实验结果表明:―OCF_(3)的引入明显提高了CPI薄膜的综合性能,TFMOB与TFMB的摩尔比为3:7时,在400~760 nm可见光波长范围内,透光率大于85%;5%质量损失对应的热分解温度(N2氛围)在530℃以上;10 GHz频率下的介电常数为2.647,介电损耗为0.00525;拉伸强度达(111.2±1.1)MPa,断裂伸长率为(67.0±5.0)%,吸湿率最低可达0.29%.证明含―OCF_(3)基团的TFMOB单体为高综合性能CPI薄膜的制备提供了可能,在柔性光学材料方面具有良好的应用前景.

An Inverse Design Method for Non-uniform Flow Inlet with a Given Shock Wave

For the hypersonic inlet and fore-body integrated design, the non-uniform incoming flow generated by the fore-body will bring a relatively big challenge to the inward-turning inlet design. To make the inlet match the non-uniform incoming flow, this paper, based on previous studies, develops a cross-stream marching plus(CSMP) method, by which an aerodynamic surface used to generate a given shock shape can be acquired.The method can correct such solution points as may give rise to grid distortions or flow-field abnormity and overcome the shortcoming of the insufficient stability of previous methods. Numerical simulation results of the conical supersonic flowfield show that the error obtained from the proposed CSMP method drops with the reduction of the grid dimension and the marching step, being less than 0.05% for reducing the marching step to 10%; that with this method the maximum relative error of the pressure on the profile is less than 0.23%. In the design process of the inward-turning inlets that match the fuselage fore-body, it's found that in comparison with the results of the inviscid CFD results, the aerodynamic surface designed with the CSMP method can fully generate the given shock wave shape. Thus, the CSMP method provides a new direction for the inlet/fore-body integrated design.