Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloeemodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-a and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction

Objective: To study the effect of Butylphthalide combined with Urinary Kallidinogenase on the pathological course of nerve damage in patients with massive cerebral infarction. Methods:The patients with massive cerebral infarction who received treatment in our hospital between January 2016 and December 2017 were selected and randomly divided into the group A receiving Butylphthalide treatment, the group B receiving Urinary Kallidinogenase treatment and the group C receiving Butylphthalide combined with Urinary Kallidinogenase treatment on the basis of conventional treatment. 14 d after treatment, serum levels of nerve markers, coagulation indexes, growth factors and oxidative stress indexes were determined. Results:After treatment, visinin-like protein-1 (VILIP-1), neuron-specific enolase (NSE), S100B protein (S100B), thromboxane A2 (TXA2), lysophosphatidic acid (LPA), D-dimer (D-D), 8-isoprostanes F2α (8-iso-PGF2α) and malondialdehyde (MDA) levels of 3 groups significantly decreased whereas nitric oxide (NO), nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) levels significantly increased, and VILIP-1, NSE, S100B, TXA2, LPA, D-D, 8-iso-PGF2α and MDA levels of the group C after treatment were significantly lower than those of the group A and group B whereas NO, NOS, VEGF, BDNF, IGF-I, SOD and T-AOC levels were significantly higher than those of the group A and group B. Conclusion: Butylphthalide combined with Urinary Kallidinogenase is better than monotherapy in improving the pathological course of nerve damage in patients with massive cerebral infarction.

Correlation of serum Hcy metabolism with pro-inflammatory factors, chemokines and oxidative stress response in patients with senile dementia

Objective: To investigate the correlation of serum Hcy metabolism with pro-inflammatory factors, chemokines and oxidative stress response in patients with senile dementia. Methods:A total of 50 patients who were diagnosed with senile dementia in our hospital between August 2012 and June 2016 were selected as the senile dementia group, and 50 elderly patients who underwent physical examination in this hospital during the same period were selected as normal control group. The differences in serum levels of Hcy, pro-inflammatory cytokines, chemokines and oxidative stress indexes were compared between the two groups, and Pearson test was adopted to assess the correlation between serum Hcy level and illness. Results: Serum Hcy level of senile dementia group was higher than that of control group;serum pro-inflammatory cytokines IL-1, IL-6, TNF-α and CRP levels were higher than those of control group;serum chemokines MCP-1, CCL2 and RANTES levels were higher than those of control group;serum oxidative stress indexes ROS, MDA and 4-HNE contents were higher than those of control group. Pearson test showed that the serum Hcy level in patients with senile dementia was positively correlated with the levels of pro-inflammatory factors, chemokines and oxidative stress indexes. Conclusions: The serum Hcy metabolism disorder in patients with senile dementia is closely related to the inflammatory response and oxidative stress response.

原发性肺霍奇金淋巴瘤1例

原发性肺霍奇金淋巴瘤(primary pulmonary Hodgkin's lymphoma,PPHL)是一种罕见的肺部肿瘤。本文报告年轻患者PPHL 1例,旨在强调年轻患者临床表现为肺部肿块时应该考虑PPHL的鉴别诊断,同时强调全身的影像学检查以排除外周累及的必要性。1临床资料患者男性,35岁,2018年5月因咳嗽1个月就诊于当地医院,检查后考虑大叶性肺炎可能,予以哌拉西林他唑巴坦和左氧氟沙星治疗后并无好转,遂于2018年6月就诊于中南大学湘雅医院。

Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury

AIM To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction(SJD) in rats with acute pancreatitis(AP) for protecting against multiple organ injury.METHODS An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group(CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD(CG + SJD) and a model group treated with SJD(MG + SJD), both of which were orally administered with SJD(5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male SpragueDawley rats were randomly divided into a CG, an AP model group(MG), and an SJD treated AP group(SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.RESULTS The MG + SJD displayed significantly shorter mean residence time(MRT) and higher clearance(CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve(AUC) for aloe-emodin; a significantly higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, interleukin(IL)-6, IL-10, and tumor necrosis factor(TNF)-α levels in the MG were higher than those in the CG(P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG(P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG(P < 0.05).CONCLUSION AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro-and antiinflammatory responses, which might guide the clinical application of SJD for AP treatment.

Elastic-viscoplastic constitutive equations of K439B superalloy and thermal stress simulation during casting process

K439B nickel-based superalloy is a new type of high-temperature material.There is insufficient research on its constitutive equations and numerical modeling of thermal stress.Isothermal tensile experiments of K439B superalloy at different temperatures(20°C-1,000°C)and strain rates(1.33×10^(-3)s^(-1)-5.33×10^(-3)s^(-1))were performed by using a Gleeble-3800 simulator.The elastic moduli at different temperatures(20°C-650°C)were measured by resonance method.Subsequently,stress-strain curves were measured for K439B superalloy under different conditions.The elastic-viscoplastic constitutive equations were established and the correspongding parameters were solved by employing the Perzyna model.The verification results indicate that the calculated values of the constitutive equations are in good agreement with the experimental values.On this basis,the influence of process parameters on thermal stress was investigated by numerical simulation and orthogonal experimental design.The results of orthogonal experimental design reveal that the cooling mode of casting has a significant influence on the thermal stress,while pouring temperature and preheating temperature of shell mold have minimal impact.The distribution of physical fields under optimal process parameters,determined based on the orthogonal experimental design results,was simulated.The simulation results determine separately the specific positions with maximum values for effective stress,plastic strain,and displacement within the casting.The maximum stress is about 1,000.0 MPa,the plastic strain is about 0.135,and the displacement is about 1.47 mm.Moreover,the distribution states of thermal stress,strain,and displacement are closely related to the distribution of the temperature gradient and cooling rate in the casting.The research would provide a theoretical reference for exploring the stress-strain behavior and numerical modeling of the effective stress of the alloy during the casting process.

Effects of Ag,Co,and Ge additions on microstructure and mechanical properties of Be-Al alloy fabricated by investment casting

The effects of Ag,Co,and Ge additions on microstructure and mechanical properties of Be-35Al(wt.%)alloys fabricated by investment casting were studied.The results reveal that the trace metals 1.5wt.%Ag,0.7wt.%Co,and 0.8wt.%Ge additions do not change the nucleation temperature of Be phase.However,the nucleation temperature of the Al phase decreases from 642℃ to 630℃ by DSC due to the Ge addition.The strength of the alloys sharply increases due to the dissolution of the Ag and Ge solutes into the Al phase and the Co into the Be phase characterized by SEM and EDS.Obviously,the strength of Be-Al-Ag-Co-Ge alloy is improved by the solution strengthening.Furthermore,a few Ag_(3) Al particles contribute to the strength of the Al phase.Be-Fe-Al ternary intermetallic compounds which can effectively reduce the negative effect of an impurity element Fe on the mechanical properties of Be-Al alloys are also found by XRD and EDS.

Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway

Objective:Myocardial ischemia/reperfusion injury(MIRI)is an obstacle to the success of cardiac reperfusion therapy.This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway.Methods:Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery,and administered luteolin.The myocardial infarct size,myocardial enzyme levels,and cardiac function were measured.Latent targets and signaling pathways were screened using network pharmacology and molecular docking.Then,proteins related to the p53 signaling pathway,apoptosis and oxidative stress were measured.Hypoxia/reoxygenation(HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro.In addition,a p53 agonist and an inhibitor were used to investigate the mechanism.Results:Luteolin reduced the myocardial infarcted size and myocardial enzymes,and restored cardiac function in MIRI mice.Network pharmacology identified p53 as a hub target.The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties.Additionally,luteolin halted the activation of p53,and prevented both apoptosis and oxidative stress in myocardial tissue in vivo.Furthermore,luteolin inhibited cell apoptosis,JC-1 monomer formation,and reactive oxygen species elevation in HR-incubated HL1 cells in vitro.Finally,the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model,and both luteolin and the p53 inhibitor pifithrin-a demonstrated a similar therapeutic effect in the MIRI mice.Conclusion:Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.Please cite this article as:Zhai P,Ouyang XH,Yang ML,Lin L,Li JY,Li YM,Cheng X,Zhu R,Hu DS.Luteolin protects against myocardial ischemia/reperfusion injury by reducing oxidative stress and apoptosis through the p53 pathway.J Integr Med.2024;22(6):652–664.

Hydrogen-Bonded Engineering Enhancing Phase Transition Temperature in Molecular Perovskite Ferroelastic

The broad operating temperature range is sought for molecular ferroic materials who are expected to be applied to flexible and electronic materials.Hydrogen bonds,an effective force between molecules,are important to regulate the molecule structure and their condition,helping a higher temperature range for ferroic materials.Here,we report a molecular perovskite ferroelastic(Me-Hdabco)Rb[BF_(4)]_(3)(Me-Hdabco=N-methyldabconium)which shows high temperature(T_(1)=322.5 K and T_(2)=381K)ferroelastic phase transitions.The ferroelastic phase transition temperature range of(Me-Hdabco)Rb[BF_(4)]_(3) is significantly increased by 71 K compared with[Meda-bco-F]Rb[BF_(4)]_(3)(Medabco-F=1-fluoro-4-methyl-1,4-diazoniabicyclo[2.2.2]octane).Structural analysis and thermal analysis demonstrate the ferroelastic phase transition is mainly attributed to dynamic cations order and disorder transformation.Therefore,new hydrogen bonds generated between cations and the Rb_(8)[BF_(4)]_(12) frame increase their intermolecular force,which is beneficial to improving the phase transition temperature.This finding has an important impact on the utilization of weak interactionforces to design and optimize functional materials.

Anions Distorting Triggering Ferroelectricity in a Molecular Crystal

Recently,molecular ferroelectrics have attracted more and more attention due to their structural diversity,low cost of manufacture,and environmental-friendly processing.However,most of the design strategies for molecular ferroelectrics have focused on the selection and modification of cations,and the use of anions has been rarely reported.Here,introducing distorted[CuBr_(4)]^(2-) tetrahedra,we obtained a high curie temperature(T_(c))ferroelectric,[cyclopentylammonium]_(2)CuBr_(4),with a T_(c) as high as 393 K,and exceeding commercial and most of reported molecular ferroelectric BaTiO_(3)(393 K).Variable-temperature hysteresis loop shows the nonlinear P-E loop of the crystal under a wide temperature range.Variable-temperature single-crystal X-ray diffraction revealed that the Aizu expression can be written as mmmFmm2.In short,this work will inspire more creative strategies by exploiting the tunability of the anion module.

A Conductive Dinuclear Cuprous Complex Mimicking the Active Edge Site of the Copper(100)/(111)Plane for Selective Electroreduction of CO_(2) to C_(2)H_(4) at Industrial Current Density

Inorganic solids are a kind of important catalysts,and their activities usually come from sparse active sites,which are structurally different from inactive bulk.Therefore,the rational optimization of activity depends on studying these active sites.Copper is a widely used catalyst and is expected to be a promising catalyst for the electroreduction of CO_(2) to C_(2)H_(4).