Approximately 30%-40% of epilepsy patients do not respond well to adequate anti-seizure medications (ASMs), a condition known as pharmacoresistant epilepsy. The management of pharmacoresistant epilepsy remains an intractable issue in the clinic. Its early prediction is important for prevention and diagnosis. However, it still lacks effective predictors and approaches. Here, a classical model of pharmacoresistant temporal lobe epilepsy (TLE) was established to screen pharmacoresistant and pharmaco-responsive individuals by applying phenytoin to amygdaloid-kindled rats. Ictal electroencephalograms (EEGs) recorded before phenytoin treatment were analyzed. Based on ictal EEGs from pharmacoresistant and pharmaco-responsive rats, a convolutional neural network predictive model was constructed to predict pharmacoresistance, and achieved 78% prediction accuracy. We further found the ictal EEGs from pharmacoresistant rats have a lower gamma-band power, which was verified in seizure EEGs from pharmacoresistant TLE patients. Prospectively, therapies targeting the subiculum in those predicted as "pharmacoresistant" individual rats significantly reduced the subsequent occurrence of pharmacoresistance. These results demonstrate a new methodology to predict whether TLE individuals become resistant to ASMs in a classic pharmacoresistant TLE model. This may be of translational importance for the precise management of pharmacoresistant TLE.
Epilepsy, Temporal Lobe/diagnosis* ; Animals ; Drug Resistant Epilepsy/drug therapy* ; Electroencephalography/methods* ; Rats ; Anticonvulsants/pharmacology* ; Neural Networks, Computer ; Male ; Humans ; Phenytoin/pharmacology* ; Adult ; Disease Models, Animal ; Female ; Rats, Sprague-Dawley ; Young Adult ; Convolutional Neural Networks

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

ObjectiveTo observe the clinical efficacy and safety of Zhuyuwan in the treatment of hyperlipidemia. MethodsIn this study， hyperlipidemia patients treated in the Hospital of Chengdu University of Traditional Chinese Medicine （TCM） from September 2022 to December 2023 were randomly assigned into a control group and an observation group. Finally， 162 valid cases were included， encompassing 74 cases in the control group and 88 cases in the observation group. The control group was treated with atorvastatin calcium tablets， and the observation group with atorvastatin calcium tablets + Zhuyuwan extract granules. Both groups were treated for 8 weeks. The efficacy in terms of blood lipid level recovery， blood lipid levels， TCM syndrome distribution， efficacy in terms of TCM syndrome， and TCM symptom scores were compared between the two groups as well as between before and after treatment. Liver and kidney functions were monitored for safety assessment. ResultsIn terms of blood lipid level recovery， the total response rate in the observation group was 86.36% （76/88） and that in the control group was 86.49% （64/74）， with no statistically significant difference between the two groups. After treatment， both groups showed declines in levels of triglyceride （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） （P<0.05） and elevations in the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）. Moreover， the observation group outperformed the control group in recovering the levels of TG， LDL-C， and HDL-C （P<0.05， P<0.01）. In terms of TCM syndrome， hyperlipidemia was mostly caused by phlegm turbidity and obstruction. The total response rate in terms of TCM syndrome in the observation group was 87.30% （55/63）， which was higher than that （63.46%， 33/52） in the control group （χ²=9.102， P<0.01）. After treatment， the scores of total TCM symptoms， primary symptoms， and secondary symptoms decreased in both groups （P<0.05）， and the observation group had lower scores than the control group （P<0.01）. The observation group was superior to the control group in alleviating obesity， chest tightness， and low food intake （P<0.05）. In terms of safety， the level of aminotransferase was slightly elevated in the control group， and no obvious adverse reaction was observed in the observation group， with no statistical significance in the incidence of adverse reactions. ConclusionZhuyuwan combined with atorvastatin can not only recover blood lipid levels and alleviate TCM symptoms but also reduce the occurrence of adverse reactions.

OBJECTIVE T o explore the action mechanisms of Ganghuo Qingwen granules(GHQWG)in treatment of influenza based on network pharmacology and molecular docking technique.METHODS The TCMSP database was logged in to search for active compounds,targets of GHQWG and targets of influenza so as to screen out the intersected targets between HGQWG and influenza and establish a drug-ingredient-target network.The poten-tial mechanisms were analyzed by means of protein-protein interaction analysis,Gene Ontology(GO)function an-notation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the activity of binding the key targets with ingredients was validated by molecular docking.RESULTS GHQWG contained 90 types of po-tential active ingredients,312 active ingredient targets,1996 influenza targets and 134 intersection targets.The core ingredients included quercetin,kaempferol and luteolin;the key targets involved V-Rel reticuloendotheliosis viral oncogene homolog A(RELA),tumor protein 53(TP53),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),serine/threonine kinase proteins 1(AKT1)and mitogen-activated protein kinase 1(MAPK1).The function enrichment showed that GHQWG could regulate the processes of gene expression,in-flammatory reaction and apoptosis.The result of KEGG indicated that GHQWG played therapeutic effect on influ-enza mainly through C type agglutinin receptor,TNF and in terleukin-17(IL-17)signaling pathway.The molecu-lar docking analysis showed that RELA,TP53,M APK3,TNF,AKT1 and M APK1 had strong activities of bind-ing with quercetin,kaempferol,luteolin,β-sitosterol,wogonin,stigmasterol,caffeic acid and isorhamnetin.CONCLUSION GHQWG may regulate the key targets of signaling pathways of C type agglutinin receptor,TNF and IL-17 through multiple ingredients-multiple targes-multiple pathway mechanisms so as to play the therapeutic effect on influenza.

Lipid turbidity disease is a metabolic disease featuring lipid metabolism disorders caused by many factors such as social environment， diet， and lifestyle， which is closely related to many diseases in modern medicine， such as hyperlipidemia， obesity， fatty liver， atherosclerosis， metabolic syndrome， and cardiovascular and cerebrovascular diseases， with a wide range of influence and far-reaching harm. According to the Huangdi Neijing， lipid turbidity disease reflects the pathological change of the body's physiologic grease. Grease is the thick part of body fluids， which has the function of nourishing， and it is the initial state and source of important substances in the human body such as brain， marrow， essence， and blood. Once the grease of the human body is abnormal， it can lead to lipid turbidity disease. The Huangdi Neijing also points out the physiological relationship between the transportation and transformation of body fluids and the rise and fall of the spleen and stomach， which can deduce the pathological relationship between the occurrence of lipid turbidity disease and the abnormal rise and fall of the spleen and stomach functions. Lipid turbidity disease is caused by overconsumption of fatty and sweet foods or insufficient spleen and stomach endowments， leading to disorders of the function of promoting clear and reducing turbidity in the spleen and stomach. This leads to the transformation of thick grease in body fluids into lipid turbidity， which accumulates in the body's meridians， blood vessels， skin pores， and organs， forming various forms of metabolic diseases. The research team believed that the pathological basis of lipid turbidity disease was the abnormal rise and fall of the spleen and stomach and the obstruction of the transfer of grease. According to the different locations where lipid turbidity stays， it was divided into four common pathogenesis types： ''inability to distinguish between the clear and turbid， turbid stagnation in the Ying blood''， ''spleen not rising clear， turbid accumulation in the vessels''， ''spleen dysfunction， lipid retention in the pores''， ''spleen failure to transportation and transformation， and grease accumulation in the liver''. According to the pathogenesis， it could be divided into four common syndromes， namely， turbid stagnation in the Ying blood， turbid accumulation in the vessels， lipid retention in the pores， and grease accumulation in the liver， and the corresponding prescriptions were given for syndrome differentiation and treatment， so as to guide clinical differentiation and treatment of the lipid turbidity disease.

OBJECTIVE To observe the fever-reducing effect of pricking-cupping method on endotoxin-induced fever in rab-bits,and to further explore the fever-reducing mechanism of pricking-cupping method from the perspective of skeletal muscle mito-chondrial energy metabolism.METHODS A total of 72 rabbits were randomly divided into blank group,model group,Western medi-cine group,pricking group,cupping group and pricking-cupping group,with 12 rabbits in each group.The rabbit model of endotoxin-in-duced fever was reproduced and the corresponding therapeutic intervention was carried out.The body temperature of rabbits was recor-ded continuously for 6 h.The mitochondrial structure was observed by transmission electron microscopy.Oxygraph-2k system was used to detect mitochondrial function.ATP content in thigh muscle tissue of rabbits in each group was detected.The expression of uncoupling protein 2(UCP2)and mitochondrial fusion protein 2(Mfn2)in thigh muscle of rabbits was detected by Wes automated western blot quantitative analysis system.RESULTS The model was successfully replicated,and the body temperature of rabbits in the four treatment groups was lower than that in the model group.The skeletal muscle mitochondrial morphology of rabbits in the blank group was intact,and the mitochondrial morphology was closest to normal after the treatment of pricking-cupping.Moreover,the oxygen con-sumption of mitochondrial CII OXPHOS stage in the pricking-cupping group was significantly higher than that in the model group.Compared with the model group,the ATP content in the muscle tissue of rabbits in the pricking-cupping group was significantly increased,Mfn2 protein expression was significantly increased,and UCP2 protein expression was significantly decreased.CONCLU-SION The pricking-cupping method has a good fever-reducing effect on endotoxin-induced fever in rabbits,and its mechanism may be related to inhibiting UCP2 protein expression in skeletal muscle,promoting Mfn2 protein expression,promoting the oxidative phos-phorylation process in skeletal muscle mitochondria,and increasing ATP synthesis in mitochondria.

OBJECTIVE T o explore the action mechanisms of Ganghuo Qingwen granules(GHQWG)in treatment of influenza based on network pharmacology and molecular docking technique.METHODS The TCMSP database was logged in to search for active compounds,targets of GHQWG and targets of influenza so as to screen out the intersected targets between HGQWG and influenza and establish a drug-ingredient-target network.The poten-tial mechanisms were analyzed by means of protein-protein interaction analysis,Gene Ontology(GO)function an-notation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the activity of binding the key targets with ingredients was validated by molecular docking.RESULTS GHQWG contained 90 types of po-tential active ingredients,312 active ingredient targets,1996 influenza targets and 134 intersection targets.The core ingredients included quercetin,kaempferol and luteolin;the key targets involved V-Rel reticuloendotheliosis viral oncogene homolog A(RELA),tumor protein 53(TP53),mitogen-activated protein kinase 3(MAPK3),tumor necrosis factor(TNF),serine/threonine kinase proteins 1(AKT1)and mitogen-activated protein kinase 1(MAPK1).The function enrichment showed that GHQWG could regulate the processes of gene expression,in-flammatory reaction and apoptosis.The result of KEGG indicated that GHQWG played therapeutic effect on influ-enza mainly through C type agglutinin receptor,TNF and in terleukin-17(IL-17)signaling pathway.The molecu-lar docking analysis showed that RELA,TP53,M APK3,TNF,AKT1 and M APK1 had strong activities of bind-ing with quercetin,kaempferol,luteolin,β-sitosterol,wogonin,stigmasterol,caffeic acid and isorhamnetin.CONCLUSION GHQWG may regulate the key targets of signaling pathways of C type agglutinin receptor,TNF and IL-17 through multiple ingredients-multiple targes-multiple pathway mechanisms so as to play the therapeutic effect on influenza.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

Sepsis is a systemic inflammatory response triggered by infection and often leads to acute kidney injury(AKI).The pathogenesis of sepsis-associated AKI is complex,involving multiple factors such as renal ischemia,inflammation and oxidative stress.In recent years,pyroptosis,a pro-inflammatory form of programmed cell death,has gradually attracted the attention of researchers.Pyroptosis is activated by inflammasomes(e.g.,the NOD-like receptor pyrin domain-related protein 3 inflammasome,NLRP3 inflammasome),accompanied by Gas-dermin D(GSDMD)-mediated formation of cell membrane pores and release of cellular contents,which leads to exacerbation of local and systemic inflammatory responses.The mechanism of pyroptosis in sepsis-associated AKI has not been fully elucidated,but AKI is directly involved in the process of renal functional impairment by indu-cing the death of renal tubular epithelial cells and exacerbating the local inflammatory response.Blockade of key molecules in the pyroptosis pathway,such as GSDMD or NLRP3 inflammasome,can significantly alleviate renal injury,suggesting that the pyroptosis pathway may be a potential therapeutic target for sepsis-associated AKI.This review summarizes the recent research progress on pyroptosis in sepsis-associated AKI,and discuss its cen-tral role in the pathogenesis,particularly focusing on the inflammasome and GSDMD pathways.Additionally,this paper analyzes the potential of focal death inhibition as a therapeutic strategy and proposes future research direc-tions with the expectation of providing references for the treatment of sepsis-related AKI.

OBJECTIVE To observe the fever-reducing effect of pricking-cupping method on endotoxin-induced fever in rab-bits,and to further explore the fever-reducing mechanism of pricking-cupping method from the perspective of skeletal muscle mito-chondrial energy metabolism.METHODS A total of 72 rabbits were randomly divided into blank group,model group,Western medi-cine group,pricking group,cupping group and pricking-cupping group,with 12 rabbits in each group.The rabbit model of endotoxin-in-duced fever was reproduced and the corresponding therapeutic intervention was carried out.The body temperature of rabbits was recor-ded continuously for 6 h.The mitochondrial structure was observed by transmission electron microscopy.Oxygraph-2k system was used to detect mitochondrial function.ATP content in thigh muscle tissue of rabbits in each group was detected.The expression of uncoupling protein 2(UCP2)and mitochondrial fusion protein 2(Mfn2)in thigh muscle of rabbits was detected by Wes automated western blot quantitative analysis system.RESULTS The model was successfully replicated,and the body temperature of rabbits in the four treatment groups was lower than that in the model group.The skeletal muscle mitochondrial morphology of rabbits in the blank group was intact,and the mitochondrial morphology was closest to normal after the treatment of pricking-cupping.Moreover,the oxygen con-sumption of mitochondrial CII OXPHOS stage in the pricking-cupping group was significantly higher than that in the model group.Compared with the model group,the ATP content in the muscle tissue of rabbits in the pricking-cupping group was significantly increased,Mfn2 protein expression was significantly increased,and UCP2 protein expression was significantly decreased.CONCLU-SION The pricking-cupping method has a good fever-reducing effect on endotoxin-induced fever in rabbits,and its mechanism may be related to inhibiting UCP2 protein expression in skeletal muscle,promoting Mfn2 protein expression,promoting the oxidative phos-phorylation process in skeletal muscle mitochondria,and increasing ATP synthesis in mitochondria.